,Unnamed: 0.2,Unnamed: 0.1,Unnamed: 0,nct_id,last_update_submitted_date,brief_title,official_title,acronym,study_type,description,criteria,active,phase_1,phase_2,phase_3,phase_4,not_applicable,minimum_age,maximum_age,predicted_cancer_type,predicted_cancer_type_official,forbidden_for_men,forbidden_for_women,sex
0,0,0,25,NCT00781612,2023-10-12,a safety extension study of trastuzumab emtansine in participants previously treated with trastuzumab emtansine alone or in combination with other anti-cancer therapy in one of the parent studies,"an open-label, multicenter extension study of trastuzumab emtansine administered as a single agent or in combination with other anti-cancer therapies in patients previously enrolled in a genentech and/or f. hoffmann-la roche ltd-sponsored trastuzumab emtansine study",,interventional,"this is a global, multicenter, open-label safety extension study. participants receiving single-agent trastuzumab emtansine or trastuzumab emtansine administered in combination with other anti-cancer therapies in a genentech / roche-sponsored parent study who are active and receiving benefit at the closure of parent study are eligible for continued treatment in this study.","inclusion criteria:

completed single-agent trastuzumab emtansine or combination trastuzumab emtansine treatment in the parent study or who continue to receive single-agent trastuzumab emtansine or combination trastuzumab emtansine treatment at the time of the parent study closure and received the last study drug dose within the 6 weeks (42 days) prior to the first dose of study therapy on the extension study or continue to receive treatment in the control arm of study bo21976/tdm4450g (nct00679341) at the time of the parent study closure if the participant received the last dose of control arm study drug within the 6 weeks (42 days) prior to the first dose of control arm study therapy in the extension study
participants in the control arm from study bo21976/tdm4450g whose disease progression has occurred during the transition interval between the parent study and this extension study may initiate trastuzumab emtansine treatment at the time of enrollment into study tdm4529g (nct00781612)
expectation by the investigator that the participant may continue to benefit from additional single-agent trastuzumab emtansine or combination trastuzumab emtansine treatment or expectation of the investigator that the participant may continue to benefit from control arm treatment as given in study bo21976/tdm4450g and at the time of disease progression may benefit from single-agent trastuzumab emtansine treatment
women of childbearing potential and men with partners of childbearing potential, must be willing to use a highly effective form of non-hormonal contraception or two effective forms of non-hormonal contraception by the participants and/or partner, and to continue the use of contraception for the duration of study treatment and for at least 5 months after the final dose of atezolizumab (if applicable) or 7 months after the final dose of trastuzumab emtansine or pertuzumab, whichever is later. women must refrain from donating eggs during this same period
male participants whose partners are pregnant should use condoms for the duration of the pregnancy. men must refrain from donating sperm during this same period

exclusion criteria:

aes leading to single-agent trastuzumab emtansine or combination trastuzumab emtansine treatment discontinuation in the parent study
ongoing saes from the parent study
progressive disease on single-agent trastuzumab emtansine or a trastuzumab emtansine-containing regimen during the parent study or before starting the extension study, with the exception of participants from study tdm4688g (nct00943670) with early disease progression who went on to receive pertuzumab + trastuzumab emtansine treatment and have not experienced further disease progression on the combination regimen
peripheral neuropathy of grade greater than or equal to (>/=) 3 per the national cancer institute common terminology criteria for adverse events (nci ctcae), version 3.0, 4.0 or 5.0, as utilized in the parent study
history of symptomatic congestive heart failure ([chf]; new york heart association [nyha] classes ii-iv), ventricular arrhythmia requiring treatment, current unstable angina, or history of myocardial infarction within 6 months prior to study entry
severe dyspnea at rest due to complications of advanced malignancy or current requirement for continuous oxygen therapy
current severe, uncontrolled systemic disease (for example [e.g.] clinically significant cardiovascular, pulmonary, or metabolic disease)
major surgical procedure or significant traumatic injury within 28 days prior to study entry or anticipation of the need for major surgery during the course of study treatment
current pregnancy or lactation
history of receiving any investigational treatment or other systemic therapy directed at controlling cancer (e.g., chemotherapy, trastuzumab, etc.) since the participant's last study drug dose in the parent study
history of hypersensitivity with previous trastuzumab emtansine or any agent used with trastuzumab emtansine in the parent study, precluding further dosing
assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol",1,0,1,0,0,0,0.0,200.0,Pleura,Other,0,1,All
1,1,1,26,NCT00819208,2023-10-13,health education materials with/out a physical activity program for patients who have undergone treatment for high-risk stage ii or stage iii colon cancer,a phase iii study of the impact of a physical activity program on disease-free survival in patients with high-risk stage ii or stage iii colon cancer: a randomized controlled trial,CHALLENGE,interventional,"rationale: participating in a physical activity program designed to increase free time physical activity and receiving written health education materials may influence the chance of cancer recurring as well as impact on physical fitness, psychological well-being and the quality of life of patients who have undergone surgery and chemotherapy for colon cancer. it is not yet known whether giving a physical activity program together with health education materials is more effective than giving health education materials alone for patients who have undergone colon cancer treatment.

purpose: this randomized phase iii trial is studying a physical activity program given together with health education materials to see how well it works compared with giving health education materials alone for patients who have undergone treatment for high-risk stage ii or stage iii colon cancer.","disease characteristics:

completely resected histologically confirmed adenocarcinoma of the colon

high-risk stage ii disease, including one of the following:

t4 lesions
less than 12 sampled lymph nodes
poorly differentiated histology
stage iii disease, defined as having at least one pathologically confirmed positive lymph node or one pathologically confirmed positive tumour deposit.
synchronous primary colon cancer allowed
adjuvant chemotherapy treatment for colon cancer with a 5-fluorouracil- based regimen received with an intent to provide a complete course of treatment. while one current standard is 24 weeks of treatment, patients who are pre-planned to receive a shorter duration of chemotherapy, including as part of a research study will also be permitted. the actual treatment received may be less than 24 weeks; participants must have received a minimum of one treatment cycle.
chemotherapy must have been completed (i.e. last dose received) a minimum of 60 days and a maximum of 180 days prior to registration.
carcinoembryonic antigen (cea) ≤ 5 μg/l
current physical activity levels do not meet the recommended guidelines (≥ 150 minutes of moderate-to-vigorous or ≥ 75 minutes of vigorous physical activity/week) as calculated using the leisure time exercise questionnaire (lteq)
completion of chest x-ray or ct, and ct, mri or ultrasound of abdomen within 60 days of registration; these imaging tests must not show evidence of metastatic or locally-recurrent colon cancer.
complete one of the following: (a) at least 2 stages of the submaximal exercise test with an acceptable heart rate and blood pressure response as defined in appendix xii or (b) the 6 minute walk test with an acceptable heart rate and blood pressure response
no rectal cancer

patient characteristics:

ecog performance status 0-1
absolute granulocyte count ≥ 1,000/mm³
platelet count ≥ 100,000/mm³
hemoglobin ≥ 100 g/l
serum creatinine ≤ 1.5 times upper limit of normal (uln)
total bilirubin ≤ 1.5 times upper limit of normal (uln)
alkaline phosphatase < 2.5 times uln
alt < 2 times uln
not pregnant or planning to become pregnant within the next 3 years
able (i.e., sufficiently fluent) and willing to effectively communicate with the physical activity consultant affiliated with the originating cancer center
able (i.e., sufficiently fluent in english or french) and willing to complete the patient-reported outcome questionnaires, social determinants of exercise measurement, health economics, and physical activity questionnaires and logs
able to complete the baseline exercise test
no significant comorbid conditions precluding participation in a physical activity program as determined by the investigator
likely to participate in a physical activity program, as assessed by the investigator
no history of other malignancies, except adequately treated nonmelanoma skin cancer, curatively treated in situ cancer of the cervix, other solid tumors, hodgkin lymphoma, or non-hodgkin lymphoma curatively treated with no evidence of disease for > 5 years

prior concurrent therapy:

see disease characteristics
no prior radiotherapy as a component of treatment for primary tumor
no concurrent treatment with additional chemotherapy or radiation
no concurrent treatment with any medications deemed by the investigator as likely to preclude participation in a physical activity program
no concurrent anticancer treatment including chemotherapy, biological, or targeted agents",1,0,0,0,0,1,18.0,200.0,Colon,Colon,0,0,All
2,2,2,29,NCT00887146,2023-10-30,radiation therapy with concomitant and adjuvant temozolomide versus radiation therapy with adjuvant pcv chemotherapy in patients with anaplastic glioma or low grade glioma,phase iii intergroup study of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy with adjuvant pcv chemotherapy in patients with 1p/19q co-deleted anaplastic glioma or low grade glioma,,interventional,"radiation therapy uses high-energy x-rays to kill tumor cells. drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. it is not yet known whether giving radiation with concomitant and adjuvant temozolomide versus radiation with adjuvant pcv is more effective in treating anaplastic glioma or low grade glioma.","pre-registration inclusion criteria:

united states (us) and canadian sites:

* this review is mandatory prior to registration to confirm eligibility; patients must be willing to submit tissue samples for mandatory central pathology review submission; it should be initiated as soon after surgery as possible

tissue must have been determined to have local 1p/9q co-deletion and idh mutation prior to submission for central path review

tumor tissue must show co-deletion of chromosomes 1p and 19q; for eligibility, the 1p/19q analysis results will be accepted from the local site, as determined by either a locally available or reference laboratory (for us, must be clinical laboratory improvement act [clia] certified); acceptable methods for determination of 1p/19q loss include fluorescent in-situ hybridization (fish), by genomic sequencing or methylomic analyses; us and canadian sites must send a copy of the official report to the pathology coordinator and quality assurance specialist (qas)
tumor must also show evidence of idh mutation by immunohistochemistry or genomic analyses; this should be performed at the local site (us: performed in a clia certified laboratory); the site must send a copy of the official report to the pathology coordinator and qas

registration inclusion criteria:

newly diagnosed and =< 3 months from surgical diagnosis; patients are also eligible if they have had a prior surgical procedure > 3 months earlier for low grade glioma, as long as the patient has not received prior radiation or prior chemotherapy

histological evidence of world health organization (who) grade iii anaplastic glioma or who grade ii low grade glioma with locally diagnosed combined 1p/19q loss and the presence of an either idh1 or idh2, both as established by a local or referenced laboratory qualified for the study

* note: mixed gliomas are eligible, regardless of the degree of astrocytic or oligodendrocytic predominance, as long as the tumor is also co-deleted for 1p and 19q

patients with codeleted low grade gliomas must also be considered ""high risk"" by exhibiting one or more of the following characteristics:

age >= 40 and any surgical therapy
age < 40 with prior and subtotal resection or biopsy (i.e., anything less than gross total resection)
documented growth following prior surgery (note: patients with prior surgery cannot have received prior radiation, chemotherapy or targeted therapy)
intractable seizures
surgery (partial or gross total resection or biopsy) must be performed >= 2 weeks prior to registration; patient must have recovered adequately from the effects of surgery
absolute neutrophil count (anc) >= 1,500/mm^3 obtained =< 21 days prior to registration
platelet (plts) count >= 100,000/mm^3 obtained =< 21 days prior to registration
hemoglobin (hgb) > 9.0 g/dl obtained =< 21 days prior to registration
total bilirubin =< 1.5 x institutional upper limit of normal (uln) obtained =< 21 days prior to registration
serum glutamic oxaloacetic transaminase (sgot) (aspartate aminotransferase [ast]) =< 3 x uln obtained =< 21 days prior to registration
creatinine =< 1.5 x uln obtained =< 21 days prior to registration
negative serum or urine pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
willingness and ability to personally complete neurocognitive testing (without assistance) and willingness to complete the qol testing, (either personally or with assistance)
eastern cooperative oncology group (ecog) performance status (ps) of 0, 1 or 2
written informed consent
willingness to return to enrolling institution for follow-up during the active monitoring phase (that is, the active treatment and observation portion) of the study); patients who have been formally transferred to another active and approved site participating in this study would not need to return to the enrolling institution for this purpose
willingness to allow the provision of tissue samples for correlative research, as long as adequate tissues are available; patients will not be excluded from participation in the study, if they are willing to allow provision of tissues for the correlative research, but there are insufficient quantities of tissue for the correlative analyses (e.g., a patient otherwise eligible and willing who had biopsy only) willingness to allow the provision of blood samples for correlative research; patients are not excluded from participation in the study, if they are willing to provide the mandatory biospecimens for translational/correlative research, but for logistical reasons the specimens(s) were not obtainable or if the volume collected was insufficient

registration exclusion criteria:

the following categories are ineligible:

pregnant women
nursing women
men or women of childbearing potential who are unwilling to employ adequate contraception or contraceptive method during this study and 6 months following the completion of chemotherapy treatments
history of prior radiation therapy or chemotherapy for glioma; note: patients who have a history of prior low grade glioma (with or without a distant history of prior surgery for that glioma), but who have never received prior chemotherapy or radiation therapy for the glioma are eligible for the study
co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
concomitant serious immunocompromised status (other than that related to concomitant steroids) that would compromise the safety of the patient on the study
patients known to be human immunodeficiency virus (hiv) positive and currently receiving retroviral therapy are not eligible; note: patients known to be hiv positive, but without clinical evidence of an immunocompromised state, are eligible for the study
uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
receiving any other investigational agent that would be considered as a treatment for the primary neoplasm
other active malignancy within 5 years of registration; exceptions: non-melanotic skin cancer or carcinoma-in-situ of the cervix; note: if there is a history of prior malignancy, the patient is not eligible if they are receiving other specific treatment (with the exclusion of hormonal therapy or her-2 inhibitors) for their cancer or if they have received prior total body irradiation which included the brain
history of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
recent history of hepatitis infection or if the treating physician determined that the patient would be at significant risk of reactivation of hepatitis",1,0,0,1,0,0,18.0,200.0,Other,Pleura,0,0,All
3,3,3,45,NCT01356290,2023-04-19,"antiangiogenic therapy for children with recurrent medulloblastoma, ependymoma and atrt","a phase ii study of metronomic and targeted anti-angiogenesis therapy for children with recurrent/progressive medulloblastoma, ependymoma and atrt",MEMMAT,interventional,"patients with relapsed medulloblastoma, ependymoma and atrt have a very poor prognosis whether treated with conventional chemotherapy, high-dose chemotherapy with stem cell rescue, irradiation or combinations of these modalities. antiangiogenetic therapy has emerged as new treatment option in solid malignancies. the frequent, metronomic schedule targets both proliferating tumor cells and endothelial cells, and minimizes toxicity. in this study the investigators will evaluate the use of biweekly intravenous bevacizumab in combination with five oral drugs (thalidomide, celecoxib, fenofibrate, and alternating cycles of daily low-dose oral etoposide and cyclophosphamide), augmented with alternating courses of intrathecal etoposide and cytarabine. the aim of the study is to extend therapy options for children with recurrent or progressive medulloblastoma, ependymoma and atrt, for whom no known curative therapy exists, by prolonging survival while maintaining good quality of life. the primary objective of the memmat trial is to evaluate the activity of this multidrug antiangiogenic approach in these heavily pretreated children and young adults. additionally, progression-free survival (pfs), overall survival (os), as well as feasibility and toxicity will be examined.","inclusion criteria:

relapsed or progressive medulloblastoma, ependymoma or atrt (at least one site of untreated recurrent disease)
histological confirmation of medulloblastoma, ependymoma or atrt at diagnosis or relapse
female or male, aged from 0 to <20 years (at time of original diagnosis)
participants must have normal organ and bone marrow function (alt <5x institutional upper limit of normal, creatinine <1.5x institutional upper limit of normal for age, wbc >1000/mm3, platelets > 20,000/mm3. patients with values less than wbc 2000/mm3 or platelets 50,000/mm3 will require initiation of treatment with etoposide and cyclophosphamide at a lower starting dose as defined within the protocol.
karnofsky performance status ≥50. for infants and children less than 12 years of age, the lansky play scale ≥50% will be used
written informed consent of patients and / or parents

exclusion criteria:

active infection
vp-shunt dependency
pregnancy or breast feeding
conventional chemotherapy, antiangiogenic treatment or complete irradiation of all disease for current relapse (surgery may be performed before antiangiogenic treatment; patients with sites of disease not irradiated are still eligible for the protocol)
known hypersensitivity to any of the drugs in the protocol
active peptic ulcer
any significant cardiovascular disease not controled by standard therapy e.g. systemic hypertension
anticipation of the need for major elective surgery during the course of the study treatment
any disease or condition that contraindicates the use of the study medication/treatment or places the patient at an unacceptable risk of experiencing treatment-related complications
non-healing surgical wound
a bone fracture that has not satisfactorily healed",1,0,1,0,0,0,0.0,19.0,Brain,Brain,0,0,All
4,4,4,51,NCT01481532,2023-09-05,open label clinical trial of intravenous crotoxin part 3,open label phase i clinical trial of crotoxin in patients with advanced cancer using an intravenous route of administration,,interventional,the primary objective of the study is to assess whether human subjects can be made tolerant to intravenously administered crotoxin and achieve higher and more therapeutically effective doses levels without the previously reported adverse effects associated with bolus i.m. administration.,"subjects will:

be adult patients with histologically confirmed advanced solid tumors (excluding basal cell, colon, pancreatic and stomach cancers) who have progressed despite standard therapy, or for whom no standard therapy exists.
have an ambulatory ps (ecog 0-1).
have tumor evaluation made within 28 days before study drug administration
have completed radiotherapy or chemotherapy or any other anticancer therapy (including experimental therapy) more than 4 weeks prior to enrolment into the trial and must have recovered from all acute side effects of these treatments
have a life expectancy greater than 3 months
have an age ≥ 18 years
have normal marrow function with the following haematological parameters normal; hb ≥10g/dl, wbc ≥4.0 x10e9/l, neutrophil count ≥ 2.0 x 10e9/l and platelets ≥100 x10e9 /l
have no medically significant impairment of cardiac or respiratory functions<
have adequate hepatic function with total bilirubin 1.5 x n and transaminases < 2.5 x n (< 5 x n in case of liver metastasis).
have no history of prior severe allergic reactions to venoms
have creatinine clearance > 50 ml/min.
be on stable doses of any drugs which may affect hepatic drug metabolism or renal drug excretion (e.g.--non-steroidal anti-inflammatory drugs, barbiturates, narcotic analgesics, probenecid). such drugs should not be initiated while the patient is participating in this study.
not be pregnant or planning to become pregnant
not known to have brain metastases or leptomeningeal involvement. ct-scan or mri is not required to rule this out unless there is clinical suspicion of central nervous system involvement
not have pleural effusion/ ascites, cystic lesions or bone metastases, as the only assessable lesions
not have a history of other malignancies, except for patients with a cancer free interval of > 5 years after treatment completion, patients with prior history of adequately treated basal cell carcinoma of the skin or carcinoma in situ of the cervix
not have had recent major surgery (within 21 days).
not have a recent history of weight loss > 10% of current body weight.
not have serious intermittent medical illnesses which would interfere with the ability of the patient to carry out the treatment program.
not be on chronic steroid medication (> 20mg/day)
not have primary or paraneoplastic myasthenia gravis
be free of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule;
will agree to participate in the study prior to starting with any specific study procedure, after having signed written informed consent.
be patients of childbearing age willing to use contraceptive for the duration of the study
not live alone and live no further than approximately 30 km away from the hospital, and for the study duration have continuous access to the use of mobile telephone in case of medical emergency",0,1,0,0,0,0,18.0,75.0,Colon,Colon,0,0,All
5,5,5,58,NCT01521676,2017-09-01,predictive clinical and biological parameters in breast cancer,research of predictive clinical and biological parameters in breast cancer,BC-BIO,interventional,"research of predictive clinical and biological factors in breast cancer :

genomic, proteomic, mutation","inclusion criteria:

breast cancer
age > 18
signed informed consent

exclusion criteria:

emergency",1,0,0,0,0,1,18.0,200.0,Breast,Breast,0,1,All
6,6,6,80,NCT01689584,2022-09-01,cosegregation of variants in panel of genes,study of family cosegregation of nucleotide variants in the panel of genes to validate their use in genetic counseling,COVAR,interventional,the aim of the covar project is to classify reliably a maximum of vus of the french database in order to use them for the genetic counseling. the results obtained through this study will have a major impact on clinical management of the patients and their families conducting in some cases to propose a prophylactic surgery.,"inclusion criteria:

index cases:

a person carrying a gene variant class 3 or 4, present and selected in the families of national database of genetic group and cancer (ggc unicancer) which identifies the variations of all genes from the panel of genes of all french laboratories.
age ≥ 18 years.
signed written inform consent ""index case""

related parties:

any relative of an index case with cancer
any relative without cancer related to an index case, retained by investigators, based on family structure and degree of related compared to the index case
age ≥ 18 years
information and signature of the informed consent ""selected relatives""

exclusion criteria:

minors
persons deprived of liberty or under guardianship (including curators).
absence of signed written inform consent",1,0,0,0,0,1,18.0,200.0,Other,Other,0,0,All
7,7,7,83,NCT01704716,2020-10-21,high risk neuroblastoma study 1.8 of siop-europe (siopen),high risk neuroblastoma study 1 of siop-europe (siopen),,interventional,"this is a randomized study of the european siop neuroblastoma group (siopen) in high-risk neuroblastoma (stages 2, 3, 4 and 4s mycn-amplified neuroblastoma, stage 4 mycn non amplified > 12 months at diagnosis).

the protocol consists of a rapid, dose intensive induction chemotherapy, peripheral blood stem cell harvest, attempted complete excision of the primary tumour, myeloablative therapy followed by peripheral blood stem cell rescue, radiotherapy to the site of the primary tumour and immunotherapy (r4 randomization - isotretinoin and ch14.18/cho (dinutuximab beta, qarziba ®).), with or without s.c. aldesleukin (il-2)). patients diagnosed after the closure of r3 randomization will not be r4 randomized. for these patients the use of ch14.18/cho antibody is recommended without scil-2 as continuous infusion as standard of care outside of controlled trials. ch14.18/cho received marketing authorization by ema in may 2017 (qarziba ®).

in the induction phase, all patients receive rapid cojec following the result of the r3 randomization which was closed on june 8th, 2017 after inclusion of 630 patients as planned.

following induction treatment peripheral blood stem cell harvest (pbsch) is performed and complete excision of the primary tumour will be attempted.

patients with an inadequate metastatic response to allow bumel mat followed by pbscr at the end of induction should receive 2 tvd (topotecan, vincristine, doxorubicin) cycles.

after rapid cojec induction, localized patients will proceed to consolidation. patients aged 12-18 months at diagnosis, with stage 4 neuroblastoma, no mycn amplification and without segmental chromosomal alterations (scas) are thought to have a good prognosis and will stop treatment after induction therapy and surgery to the primary tumour.

consolidation consists of bumel mat based on the results of the r1 randomization followed by peripheral blood stem cell rescue (pbscr) and radiotherapy to the site of the primary tumour.

the r2 immunotherapy randomization using ch14.18/cho as 8 hour infusion on 5 consecutive days ( total dose (100mg/m²) with or without aldesleukin (il-2) alternated with isotretinoin (13-cis-ra) is closed.

the amended r4 immunotherapy randomization using ch14.18/cho as continuous infusion (total dose 100mg/m² over 10 days) with or without aldesleukin (il-2) alternated with isotretinoin (13-cis-ra) has accrued according to plan with results pending awaiting data maturity and dmc approval.","inclusion criteria:

• established diagnosis of neuroblastoma according to the international neuroblastoma staging system (inss).

age below 21 years.

high risk neuroblastoma defined as either:

inss stage 2, 3, 4, and 4s with mycn amplification, or
inss stage 4 without mycn amplification aged > 12 months at diagnosis
patients who have received no previous chemotherapy except for one cycle of etoposide and carboplatin (vp16/carbo). in this situation patients will receive rapid cojec induction and the first rapid cojec cycle may be replaced by the first cycle vp16/carbo (etoposide / carboplatin).
written informed consent, including agreement of parents or legal guardian for minors, to enter a randomised study if the criteria for randomisation are met.
tumour cell material available for determination of biological prognostic factors.
females of childbearing potential must have a negative pregnancy test. patients of childbearing potential must agree to use an effective birth control method. female patients who are lactating must agree to stop breast-feeding.
registration of all eligibility criteria with the data centre within 6 weeks from diagnosis.
provisional follow up of 5 years.
national and local ethical committee approval.

exclusion criteria:

any negative answer concerning the inclusion criteria of the study

-",1,0,0,1,0,0,0.0833333333333333,21.0,Brain,Pleura,0,1,All
8,8,8,85,NCT01717131,2020-01-17,axillary node dissection versus no dissection in breast cancer with positive sentinel lymph node,a non inferiority randomized multicenter phase iii trial of axillary node dissection versus no axillary node dissection in case of positive sentinel lymph node in invasive breast cancer,,interventional,"data from cohorts, prospective studies and one randomized trial (ascog z0011) support the hypothesis that omission of additional axillary dissection in case of positive sentinel node has a limited impact on overall survival and relapse free survival. however, these data are not sufficient enough to recommend, as a standard of care, to avoid axillary dissection in case of positive sentinel node. the ascog z0011 trial has been closed before the end of inclusions and the predefined non inferiority margin was found to be too large (5% difference at 5 years for primary endpoint).

prospective randomized trial is then urgently mandatory before omission of axillary node dissection becomes a usual practice without a sufficient scientific level of proof. indeed, in several reviews, the rate of omission of axillary node dissection in case of micrometastasis increased (bilimoria) despite any strong proof has been demonstrated.

the omission of axillary node dissection in case of positive sentinel node may have strong practical impacts on patients but also on medical and economical aspects: in avoiding a prolonged hospitalisation, secondary morbidities due to axillary dissection requiring secondary care and their costs, as well as costs for secondary axillary dissection (14 to 25% in case of positive sentinel node) and finally shortening surgery duration.

the main investigator propose a non inferiority randomized multicenter phase iii trial of axillary node dissection versus no axillary node dissection in case of positive sentinel lymph node in invasive breast cancer","inclusion criteria:

- patient aged 18 years and above,
- patient with invasive breast cancer histologically proven or cytologically proven by fine needle biopsy,
- patient with a unifocal tumor t0 - t1 - t2 up to 5 cm (clinical or in imagery), without previous therapy (neoadjuvant chemotherapy or hormone therapy),
- patient with clinical n0 status,
- absence of clinically detectable metastases known,

6- patients for whom conservative surgery with sentinel lymph node (sln) technique is feasible from the start in terms of carcinologic,

7 -all patients with lymph node involvement (gs+), whatever the size of the metastasis (macro-metastasis, micro-metastasis, cellular cluster or isolated tumor cells),

8 - patient affiliated to a social security system or benefiting from such a system,

9 - signed consent to participate.

exclusion criteria:

- tumor of more than 5 cm
- indication of neoadjuvant therapy by chemotherapy or hormone therapy
- history of breast cancer (ipsilateral, ie recurrence, or contralateral breast)
- history of any other invasive cancer other than a past cutaneous cancer correctly treated
- initial metastatic disease known
- presence of clinical axillary adenopathy
- contra-indication to surgical excision
- contra-indication to the sln technique
- pregnant women, of child-bearing potential, or lactating women

10- patient deprived of liberty or under supervision of a guardian

11- impossibility to undergo medical examinations of the study for geographical, social or psychological reasons.",1,0,0,1,0,0,18.0,200.0,Breast,Breast,0,1,Female
9,9,9,86,NCT01717924,2023-01-25,evaluation of surgery versus primary chemotherapy in resectable signet ring cell gastric adenocarcinoma,multicenter randomized controlled trial to evaluate the strategy of primary surgery versus primary chemotherapy in resectable signet ring cell gastric adenocarcinoma (adci002 study),ADCI002,interventional,the adci 002 trial is a large multicenter phase ii-iii prospective randomized controlled trial comparing primary surgery versus primary chemotherapy followed by surgery in patients with a resectable signet ring cell gastric adenocarcinoma,"inclusion criteria:

adenocarcinoma of the stomach or the oesogastric junction of type iii of siewert classification,histologically proven with the presence of signet ring cells (according to who 2000 classification) or diffuse form (according to lauren classification) on pre-therapeutic biopsies
tumoural stage ib, ii or iii (according to uicc-ajcc 2009)
patient judged resectable in a curative intent on inclusion
absence of distant metastasis
absence of peritoneal carcinomatosis during pre-treatment explorative laparoscopy
who performance status 2 or less
age over 18 or under 80 years
weight loss at the time of inclusion < 15%
neutrophilic polynuclears more than 1500/mm3
platelets more than 100000/mm3
creatinine clearance more than 50 ml/min
serum-albumin more than 30 gram/l
bilirubin less than 1,5 normal
prothrombin rate over 80%
absence of prior treatment with chemotherapy or radiotherapy for gastric cancer
absence of kniwn child b or c cirrhosis
left ventricular ejection fraction more than 50% before epirubicin treatment
extension check-up performed within 4 weeks of inclusion
signed written informed consent given by the patient

exclusion criteria:

no corresponding to the inclusion criteria
another malignant tumour treated for curative purposes during the past 5 years excepted basocellular skin carcinoma or in situ uterine cervix cancer
allergy to the active substance or one of the excipients in the study drugs
pregnancy or breast-feeding
any other concommitant treatment, immunotherapy or hormonal therapy
history of abdominal or chest radiotherapy
any evolving disorder which is not under control (liver failure, kidney failure, respiratory failure, evolving heart failure or myocardial necrosis during the past 6 months)
patients who cannot be regularly monitored",1,0,0,0,0,1,18.0,80.0,Gastric,Gastric,0,0,All
10,10,10,95,NCT01774409,2022-04-08,program to establish the genetic and immunologic profile of patient's tumor for all types of advanced cancer,program to establish the genetic and immunologic profile of patient's tumor for all types of advanced cancer,PROFILER,interventional,"it is a non-randomized, multicentric, cohort study, combined with a biological sample collection, a clinical data collection and with a genetic and immunologic biomarkers study.

the profiler program aims to implement a personalized cancer medicine approach by proposing to establish the genetic and immunologic profile of the tumor for patients with an advanced malignant tumor, in order to define a map of genetic (for the pre-identified target genes) and immunologic profiles for all the studied types of cancer. this study will also allow adapting the therapeutic management of these patients, if needed, by giving them targeted therapies or immunotherapies (commercialized on in ongoing clinical trials), based on the recommendations of the multidisciplinary molecular board.

the genetic and immunologic profile of the tumor will be determined from archival or fresh collected (biopsy of a reachable lesion) tumor sample and from a blood sample. the correlation between genetic profiles of the tumor, patients immunity status and clinical data (progression, tumor response, etc.) collected from the patient medical records will probably allow us to identify biomarkers with a potential predictive value and to determine if some genetic disorders are linked to immunity status alterations.","inclusion criteria:

histologically or cytologically confirmed diagnosis of advanced (locally-advanced or metastatic) malignant tumor of any histological type
tumor sample available to determine the genetic profile: either archival tumor sample [ffpe (formalin fixed and paraffin embedded)] or perform a new biopsy on an accessible lesion (left at the investigator's appreciation). for biopsies, presence of at least one tumor lesion with a diameter ≥ 20 mm, visible by medical imaging and accessible to repeatable percutaneous (needle biopsies 18 gauge or larger) sampling that permit core needle biopsy (ideally 4 cores) without unacceptable risk of a major procedural complication. please note that brain and bone lesions are not considered as accessible lesions.
patient with 1st, 2nd or 3rd line therapy (nb: endocrine therapy (monotherapy) are not considered as line therapy) for advanced / metastatic cancer.
for patients over 70 years of age, a performance status (ps) of 0 on the ecog scale.
patient must be covered by a medical insurance.
informed consent signed by the patient and/or by parents (or legal representative) for patients below 18.

exclusion criteria:

no tumor sample available.",1,0,0,0,0,1,0.0,200.0,Pleura,Pleura,0,0,All
11,11,11,105,NCT01804686,2023-11-08,a long-term extension study of pci-32765 (ibrutinib),"a phase 3b, multicenter, open-label, pci-32765 (ibrutinib) long-term extension study",CAN3001,interventional,"the purpose of this study is to collect long-term safety and efficacy data for participants treated with ibrutinib and to provide ongoing access to ibrutinib for participants who are currently enrolled in ibrutinib studies that have been completed according to the parent protocol, are actively receiving treatment with ibrutinib, and who continue to benefit from ibrutinib treatment.","inclusion criteria:

participants must be currently participating in an ibrutinib clinical study considered complete and have received at least 6 months of treatment with ibrutinib. at study entry, participants must be actively receiving treatment with single-agent ibrutinib; or participants must have participated in an ibrutinib randomized clinical study in which they initially received comparator treatment and now cross-over to ibrutinib. note: a minimum of 6 months requirement for prior ibrutinib treatment will not be mandatory in this case and participants with less than 6 months will be required to have more frequent initial safety assessments; or participants must be currently participating in study pci-32765lym1002. at study entry, participants must be actively receiving combination treatment with ibrutinib and nivolumab or single-agent ibrutinib
investigator's assessment that the benefit of continued ibrutinib therapy as a single agent or in combination with nivolumab will outweigh the risks
agrees to protocol-defined use of effective contraception
negative blood or urine pregnancy test at screening

exclusion criteria:

requires anticoagulation with warfarin or equivalent vitamin k antagonists
requires treatment with strong cytochrome p450 (cyp)3a4/5 inhibitors, unless previously approved by sponsor
any condition or situation which, in the opinion of the investigator, may put the participant at significant risk, may confound the study results, or may interfere significantly with volunteer's participation in the study",0,0,0,1,0,0,18.0,200.0,Brain,Brain,0,1,All
12,12,12,110,NCT01817192,2023-07-13,adjuvant chemotherapy in patients with intermediate or high risk stage i or stage iia non-squamous non-small cell lung cancer,a randomized prospective trial of adjuvant chemotherapy in patients with completely resected stage i or iia non-squamous non-small cell lung cancer identified as intermediate or high risk by a 14-gene prognostic assay,,interventional,"the optimal treatment for stage i or stage iia non-small cell lung cancer (nsclc) remains controversial. radiographic surveillance alone has been recommended for stage i and stage iia patients after the tumor is removed surgically from the lung, and this standard has been based on the fact that no previous clinical trial has demonstrated a benefit for stage i or stage iia nsclc patients who receive post-operative chemotherapy. these patients, however, have a substantial risk of death within five years after operation, ranging from approximately 30% to 45%, largely due to metastatic disease that is present immediately after surgery but that is undetectable by conventional methods. some leading organizations therefore currently recommend post-operative chemotherapy as an alternative standard of care in stage i or stage iia nsclc patients who are considered to be at particularly high-risk. up until now, however, there has not been a well-validated means to identify stage i and stage iia nsclc patients at high risk of death within five years after operation. a new prognostic tool, a 14-gene prognostic assay, which has been validated and definitively demonstrated in large scale studies to identify intermediate and high-risk stage i or stage iia patients with non-squamous nsclc, is now available to all clinicians through a clia-certified laboratory. it is therefore now possible to compare the outcomes of patients randomly assigned to one or the other of these competing standards of care.","inclusion criteria:

written informed consent

age ≥ 18 years

able to comply with the protocol, including acceptable candidacy for adjuvant chemotherapy according to local institutional standards and likely compliance with follow-up for anticipated length of study (i.e. 5 years from the initiation of enrollment).

willing to be randomized to chemotherapy.

histologically documented completely resected (r0) stage i or iia non-squamous nsclc (per 8th edition, tnm staging system)

adequate tissue sample for the 14-gene prognostic assay

life expectancy excluding nsclc diagnosis ≥ 5 years

ecog performance status 0-1

completely healed incisions",1,0,0,0,0,1,18.0,200.0,Lung,Lung,0,0,All
13,13,13,143,NCT01958762,2023-02-07,screening for cancers in the oral cavity,"screening for cancers in the oral cavity targeting tobacco users in somme, france",IDECAB,interventional,"in the somme region of france, cancer registry data showed an increasing incidence of oral cancer. the incidence rates in somme as compared to the national rates for lip, oral cavity and pharynx cancer were in 2010: 31,4/100 000 standard population versus 18,2 /100 000 for male and 8,2/100 000 versus 5,5/100 000 for female, disaster area where action to improve early detection for smokers will be assessed. this target population consults late (as 70% of oral cavity cancers are diagnosed at a late stage (t3 or t4). this project is an innovative incentive strategy for screening among general practitioners based on unusual information vectors (tobacconist, local media).

the main objective of this study is a screening of oral cavity cancers in tobacco users aged 30-75 years in the somme region of france.","inclusion criteria:

any smoker who buys a pack of cigarettes over a period of two weeks in a tobacco shop located on the territory of the somme
lives in somme departement

exclusion criteria:

-",1,0,0,0,0,1,30.0,75.0,Other,Pleura,0,0,All
14,14,14,152,NCT01976182,2023-09-13,"prospective, multicentric, phase ii randomized controlled trial on two parallel groups comparing the efficacy of two immunosuppressive drugs (methotrexate, cyclophosphamide) in large granular lymphocytes leukemia","prospective, sequential multiple assignment, multicentric, phase ii randomized controlled trial on two parallel groups comparing the efficacy of two immunosuppressive drugs (methotrexate, cyclophosphamide) in large granular lymphocytes leukemia",LGL,interventional,"lgl leukemia represents a rare subtype of chronic t or nk lymphoproliferative disorders. it is an indolent disease, the main hematological or autoimmune complications lead to a treatment in more than 60% of patients.

investigators set up at the university hospital of rennes, a database of more than 300 patients with lgl leukemia from major french services that support this disease, and published in 2010 the largest series of patients in the world (n = 229). however, the limited heterogeneity and retrospective data collected, as all previously released, makes it difficult the proposal of consensual treatment options. if first and second line treatments are based on the use of immunosuppression with methotrexate, cyclophosphamide, or cyclosporin a, no molecule has proven superiority over others. methotrexate and cyclophosphamide are mainly used in the first line. invetigators just have in the literature data on about 100 patients treated with either of these drugs. combining the results of our series with those in the literature, invetigators estimate the respective overall response rate (rg) and complete response rate (cr) in 55% and 30% for methotrexate, and 60% and 50% for cyclophosphamide.

thus, there are four objective in this study :

to compare the respective efficacies of methotrexate and cyclophosphamide when administered as first-line therapies in patients suffering from t/nk lgl leukemia with severe neutropenia or neutropenia associated with infections, and/or anemia requiring transfusions, and/or auto-immune associated disease
to evaluate the percentage of patients refractory to methotrexate or cyclophosphamide for which a second line treatment is efficacious
to explore, in case of non-response to the first-line therapy, the efficacy of ciclosporine a, the comparison being performed with the treatment which was not administered in the first-line therapy
to evaluate the response rate according to the phenotypic subtype of lgl leukemia.","inclusion criteria:

common criteria of lgl leukemia: the diagnosis is based on a chronic lgl peripheral blood expansion (>0.5x109/l), usually lasting more than 6 months

specific criteria for t-lgl leukemia or nk-lgl lymphocytosis or chronic nk-lgl leukemia:

specific criteria for t-lgl leukemia:
expression of lgl surface markers compatible with an activated t-cell (commonly alpha-beta+/cd3+/cd8+/cd57+ and/or cd16+) phenotype or gamma-delta+ t cells;

clonal rearrangement of tcrγ gene using pcr or specific and clonal vβ expression using fcm.

specific criteria for nk-lgl lymphocytosis or chronic nk lgl leukemia:
expression of lgl surface markers compatible with a nk cell (commonly cd3-/cd8+/cd16+ and/or cd16+/cd56+) phenotype;
cd56+ or cd16+ nk cells greater than 0.75x109/l;
the term of chronic nk-lgl lymphocytosis is used for patients with chronic illness (nb: patients with massive tissue lgl infiltration of the spleen, liver and bone marrow and presenting aggressive clinical behavior are considered as having aggressive nk-lgl leukemia and should not be included).
age above 18 years
ecog performance status of 0-2
life expectancy of at least 1 year
lack of previous treatment (except with g-csf or transfusions)

at least one indication of treatment:

isolated severe neutropenia (anc <0.5x109/l) or neutropenia (anc <1.5x109/l) with two or more infections requiring antibiotics;
anemia (whatever the underlying mechanism: pure red cell aplasia or marrow infiltration) requiring transfusions greater than 2 units for two months prior to inclusion, or symptomatic anemia (hemoglobin <10g/dl) with impairment of the quality of life;
associated complications such as systemic diseases or auto-immune diseases (i.e. recurrent uveitis, cutaneous vasculitis, autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, rheumatoid arthritis resistant to steroids and/or immunomodulator agents (colchicin, disulone, hydrochloroquine)) and justifying a treatment with methotrexate or cyclophosphamide
written informed consent

exclusion criteria:

inability to understand or to follow study procedures
prior or concurrent malignancy within the past 5 years except inactive nonmelanomatous skin cancer or carcinoma in situ of the cervix
other serious medical illnesses, such as hepatic, renal, cardiac, pulmonary, neurologic, or metabolic disease that would preclude the patient's ability to tolerate methotrexate, cyclophosphamide, or ciclosporine a
reactive lgl lymphocytosis (i.e. after viral infection)
alat/asat or alkalin phosphatases >3 times normal values
creatinine clairance <50 ml/min
serologic evidence of hiv, hepatitis c or hepatitis b infection
non effective contraception
positive pregnancy test
nursing woman",1,0,1,0,0,0,18.0,200.0,Lung,Pleura,0,0,All
15,15,15,153,NCT01977274,2020-06-30,predictive clinical and biological parameters in gynecological cancer,predictive clinical and biological parameters in gynecological cancer - gc-bio-ipc 2013-010,GC-BIO,interventional,"research of predictive clinical and biological factors in breast cancer : genomic, proteomic, mutation","inclusion criteria:

gynecological cancer suspicion
age > 18
signed informed consent

exclusion criteria:

- emergency

exclusion criteria after histological exam any diagnosis that is not a gynecological cancer (ovarian, cervix, endometrium).",1,0,0,0,0,1,18.0,200.0,Vulva,Vulva,0,1,Female
16,16,16,155,NCT01993498,2023-04-20,chronic toxicities related to treatment in patients with localized cancer,a cohort to quantify and to predict treatment related chronic toxicities in patients with non-metastatic cancer - breast and lung.,CANTO,interventional,"the aims of the cohort will be to quantify impact of cancer treatments toxicities , and to generate predictors of chronic toxicity in patients with non-metastatic cancer. study of the original cohort will be focused on localized breast cancer patients, other localisation in non-metastatic setting will be explored furtherwise, fist of all in lung cancer.

the project will include four specific aims :

to develop a database of chronic treatment related toxicity in a cohort of 14750 women with stage i-iii breast cancer (= non metastatic), whatever these treatments are (surgery; radiation therapy; chemotherapy …)
to describe incidence, clinical presentation, and outcome of chronic toxicities.
to describe the psychological, the social and the economic impacts of chronic toxicities.
to generate predictors for chronic toxicities in order to prevent them, based upon biological criteria.

the expected impact of these toxicities, when identified, will be to improve quality of life and to decrease health cost, by the early identification of patients at high risk of toxicity. such early identification could lead to prevent toxic effect by: a. developing prevention strategies, b. substituting toxic treatment by a non (less) toxic one.

also, such cohort will offer a quantification of the impact of treatment toxicity, that could be further used to quantify medical usefulness of strategies that aim at decreasing treatment toxicities (implementation of predictive biomarker for resistance, cytotoxic-free regimen etc…)","patient with disease ( 14550)

inclusion criteria:

women,
aged 18 years and over,
with an invasive breast cancer diagnosed by cytology or histology,
tumors ct0 to ct3, cn0-3,
no clinical evidence of metastasis at the time of inclusion,
untreated including scored for breast cancer surgery in progress,
patient receiving a social security system,
patient mastering the french language,
free and informed consent for additional biological samples, different questionnaires and collecting information on resource usage.

(since february 2022) patient :

age < 45 years at diagnostic
or ct2-3, cn0-3, her2+(rh+or rh-) or rh-her2-

exclusion criteria:

metastatic breast cancer,
local recurrence of breast cancer,
history of cancer within 5 years prior to entry into the trial other than basal cell skin or carcinoma in situ of the cervix,
already received treatment for breast cancer ongoing,
blood transfusion performed for less than six months,
persons deprived of liberty or under supervision (including guardianship).

healthy volunteers ( 200)",1,0,0,0,0,1,18.0,200.0,Pleura,Breast,0,1,Female
17,17,17,165,NCT02029001,2022-12-15,adapting treatment to the tumor molecular alterations for patients with advanced solid tumors: myownspecifictreatment,"a two-period, multicenter, randomized, open-label, phase ii study evaluating the clinical benefit of a maintenance treatment targeting tumor molecular alterations in patients with progressive locally-advanced or metastatic solid tumors",MOST plus,interventional,"the most plus study is a two-period phase ii clinical trial, conducted in patients with all types of progressive solid tumors after at least 1 prior systemic treatment regimen for advanced disease (in the absence of a validated second line therapy).

the main goal of this study is to evaluate for these patients the clinical benefit of a maintenance treatment in patients with stable disease (sd) after induction treatment with a selected therapy (molecular targeted therapy (mtt) or with sd, partial response (pr) or complete reponse (cr) with immunotherapy (it)).

for mtt, the first period of this trial (induction period) will enable to establish whether the identification of genomic alterations in genes encoding for ""actionable"" targets in the tumor cells, regardless of the histological subtype, can be used to select efficient treatment targeting the pathway activated by the mutation.

for immunotherapy, induction period with durvalumab + tremelimumab is expected to be an innovative therapy for an efficient tumor control and may allow to identify types of cancer or molecular types of cancer that are more receptive to immunotherapy.

for all treatments, the second period (maintenance period) will use a randomized design to evaluate the clinical benefit of a maintenance treatment with the targeted therapy or immunotherapy selected based on tumor molecular profile in patients treated by mtt with sd and in patients treated by it with sd, pr or cr.

each patient enrolled will receive the matching targeted therapy during 12 weeks (mtt) or 52 weeks (it). at the end of this induction period:

mtt cohorts :

patients with a tumor response (cr: complete response or pr: partial response) will continue the targeted therapy,
patients in progression will discontinue the targeted therapy and will be withdrawn from study and oriented towards standard treatments
patients with a stable disease at 12 weeks will be randomized in order to determine if they continue or stop the therapy.

it cohort :

- patients with sd, pr or cr at 52 weeks will be randomized in order to determine if they continue or stop the therapy.

for each mtt treatment group: ~80 patients treated in the first step (induction period), 50 patients randomized in the second step (maintenance period, 25 patients per arm).

for it treatment group: ~125 patients treated in the first step (induction period), 50 patients randomized in the second step (maintenance period, 25 patients per arm).

in total (for 7 treatment groups): ~ 600 patients treated in the induction period and 350 patients randomized in maintenance period.","inclusion criteria:

i1. male or female patient ≥ 18 years of age.

i2. histologically or cytologically confirmed diagnosis of metastatic or locally advanced and unresectable solid tumor of any type, except for nilotinib cohort: only pigmented villonodular synovitis are eligible, not amenable to curative treatment. concerning primitive tumors of the central nervous system (cns), all histological types of malignant tumors (including parenchymal and meningeal tumors) are eligible (except for it).

i3. documented disease progression at the time of study entry.

i4. at least one prior systemic treatment regimen for locally advanced or metastatic disease. patients who are candidates for a validated second line treatment regimen are not eligible for the study. for patients with a primitive cns tumor, the absence of other therapeutic options must be validated by the reference committee for the patient's pathology before inclusion. as there is no prior systemic treatment regimen available for locally advanced or metastatic pecoma, these tumors are eligible for a mtt treatment in first line of their advanced or metastatic disease. no previous treatment by immunotherapy is allowed for it group.

i5. patient with measurable disease, defined as at least one lesion that can be accurately measured on ct-scan or mri according to recist 1.1.

i6. a multidisciplinary molecular board must have recommended one of the investigational mtt available in the study after review of a tumor (or blood for pazopanib, olaparib and immunotherapy cohorts) molecular profiling previously established from a biopsied lesion and/or primitive tumor, and/or from a liquid biopsy, respectively (for pazopanib, olaparib and immunotherapy cohorts).

i7. the mtt recommended by the multidisciplinary molecular board after the review of tumor or blood molecular profile is not approved and reimbursed in france for the disease affecting the patient in the same label.

i8. eastern cooperative oncology group (ecog) performance status 0, 1 or 2.

i9. adequate organ system function as assessed by the following minimal laboratory requirements :

absolute neutrophil count (anc) ≥ 1 x 109/l (for pazopanib and olaparib: ≥ 1.5 x 109/l)
platelets ≥ 100 x 109/l
hemoglobin ≥ 9 g/dl. transfusion is not allowed within 7 days of screening assessment. (for olaparib: hemoglobin ≥ 10 g/dl. transfusion is not allowed within 28 days of screening assessment, no features suggestive of myelodysplastic syndrome (mds)/acute myeloid leukemia (aml) on peripheral blood smear within the 28 days)
for pazopanib: activated partial thromboplastin time (aptt) ≤ 1.2x upper limit of normal (uln) and prothrombin time (pt) or international normalized ratio (inr) ≤ 1.2x uln; subjects receiving anticoagulant therapy are eligible if their inr is stable and within the recommended range for the desired level of anticoagulation.
aspartate aminotransferase (ast) and alanine transaminase (alt) ≤ 3x uln in the absence of liver metastases (≤ 5x uln for patients with liver involvement of their cancer) and total bilirubin ≤ 1.5x uln. (for pazopanib: ast and alt ≤ 2.5x uln; concomitant elevations in bilirubin and ast or alt above 1x uln are not permitted; for olaparib and it: ast and alt ≤ 2.5x uln in the absence of liver metastases (≤ 5x uln for patients with liver involvement of their cancer) and total bilirubin ≤ 1.5x uln.).
serum creatinine ≤ 1.5x uln or creatinine clearance ≥ 50 ml/min (calculated by cockcroft-gault formula, or modification of diet in renal disease (mdrd) formula for patients older than 65 years) (for pazopanib: creatinine clearance ≥ 30 ml/min; for olaparib : creatinine clearance ≥ 51 ml/min; for it : creatinine clearance ≥ 40 ml/min )
for pazopanib: urine protein to creatinine ratio (upc) <1; if upc ≥1, 24-hour urine protein must be <1g (use of urine dipstick for renal function assessment is not acceptable).
corrected qt (qtc) interval ≤ 450 msecs (≤ 480 msecs if recommended mtt has no known effect on qt interval) on screening ecg, within 14 days prior to c1d1 (for olaparib : qtc < 470 msec on 2 or more time points within a 24 hour period on screening ecg, within 7 days prior to c1d1).

i10. life expectancy of at least 4 months.

i11. specific toxicities related to any prior anti-cancer therapy must have resolved to grade ≤1 (defined by the nci-ctcae v4.03) except for alopecia, vitiligo and fatigue. grade 2 neutropenia or anemia is accepted.

i12. women of childbearing potential must have a negative pregnancy test performed within 3 days prior to study treatment start. a positive urine test must be confirmed by a serum pregnancy test.

i13. women of childbearing potential (entering the study after a confirmed menstrual period and who have a negative pregnancy test) and men of reproductive potential must agree, if sexually active, to use two methods of medically acceptable forms of contraception during the study and for at least 8 weeks following the last treatment intake. (for olaparib : during the study and for at least 1 month for women and 3 months for men following the last treatment intake; for it : during the study and for at least 3 months following the last treatment intake). refrain from breastfeeding (for nilotinib cohort : not breast-feed for at least two weeks after the last dose of nilotinib) and egg cell donation. males should not donate sperm during or for 3 months after treatment i14. signed and dated informed consent document indicating that the patient has been informed of all the pertinent aspects of the trial prior to enrollment.

i15. the patient must be affiliated to the french social security system.

i16. the recommended study treatment must have been approved by the medical staff of the steering committee.

i17. patient should be able and willing to comply with study visits and procedures as per protocol.

i18. patient must fulfill all following conditions (criteria only applicable for durvalumab + tremelimumab cohort):

availability of a pre-treatment sample of primary tumor (only formalin-fixed paraffin-embedded (ffpe) block with sufficient material) and presence of at least one biopsiable tumor lesion for on-treatment biopsy,
weight > 50 kg,
patient with a maximum of 2 prior lines of treatment at time of c1d1 for their metastatic or locally advanced.

exclusion criteria:

patients eligible for this study must not meet any of the following criteria:

e1. previous treatment in advanced phase with an investigational therapy inhibiting the same target proteins as this recommended for the study.

e2. any contra-indication to receive the recommended mtt, including known or suspected hypersensitivity to compounds of similar chemical or biologic composition as the active substance, or to any of the excipients.

e3. for nilotinib, sorafenib, pazopanib, lapatinib and olaparib: patient with hypokalemia (< lower limit of normal) or known history of congenital long qt syndrome (qt interval prolongation).

e4. prior malignancy or presence of any other active malignancy. subjects who have had another malignancy and have been disease-free for 5 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.

e5. patient who have had major surgery or trauma within 28 days prior to first dose of investigational product. patient must have recovered from any effects of any major surgery.

e6. patient with symptomatic or uncontrolled cns metastatic involvement of his/her cancer, unless the patient have stable neurological function without evidence of cns progression within 12 weeks prior to study entry and does not require treatment with enzyme-inducing anticonvulsants or steroids. patients with a primitive tumor of the cns are not eligible to it and if one of the following conditions is fulfilled:

alteration of cognitive functions impeding the patient's comprehension of study and the provision of informed consent by the patient himself/herself.
need for supportive care treatment(s) interfering with study treatment.

e7. treatment with any of the following anti-cancer therapies prior to the first dose of study treatment: radiation therapy (for olaparib : within 3 weeks or 5 half-lives of a drug whichever is longer), surgery or tumor embolization within 14 days prior to the first dose of study treatment or immunotherapy within 28 days (except for it : patient already treated with an immunotherapy are excluded) or chemotherapy (for olaparib : within 3 weeks or 5 half-lives of a drug whichever is longer), biologic therapy, investigational therapy or hormonal therapy within 14 days or 5 half-lives of a drug (whichever is longer). palliative radiotherapy is authorized only if the irradiated field does not include target lesions.

e8. administration of any non-oncologic investigational agent within 30 days or 5 half-lives (whichever is longer) prior to receiving the first dose of study treatment.

e9. for oral treatment : patient with any condition that impairs their ability to swallow and retain tablets and may affect the absorption of the investigational product are excluded.

e10. for pazopanib: clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:

active peptic ulcer disease
known intraluminal metastatic lesion(s) with risk of bleeding
inflammatory bowel disease or other gastrointestinal conditions with increased risk of perforation
history of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.

e11. for pazopanib and it: evidence of active bleeding or bleeding diathesis. e12. for pazopanib: known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage.

lesions infiltrating major pulmonary vessels (contiguous tumour and vessels) are excluded; however, the presence of a tumor that is touching, but not infiltrating (abutting) the vessels is acceptable.
large protruding endobronchial lesions in the main or lobar bronchi are excluded; however, endobronchial lesions in the segmented bronchi are allowed.
lesions extensively infiltrating the main or lobar bronchi are excluded; however, minor infiltrations in the wall of the bronchi are allowed.

e13. for pazopanib: recent hemoptysis.

e14. any clinically significant and/or uncontrolled medical disease that could compromise the patient's ability to tolerate study treatment or would likely interfere with study procedures or results. these conditions include but are not limited to:

active clinically serious bacterial or fungal infection
history of uncontrolled or significant cardiac disease within the past 6 months: left ventricular ejection fraction (lvef) < 50%, congestive cardiac failure, active ischemic heart disease, ventricular arrhythmia, myocardial infarction within 1 year, unstable angina pectoris, cardiac surgery. (except for nilotinib, all patients with uncontrolled or significant cardiac disease are excluded)
patients with cerebrovascular accident (including transient ischemic attack), pulmonary embolism or untreated deep venous thrombosis (dvt) within the past 6 months are not eligible for pazopanib treatment group
poorly controlled hypertension [for pazopanib: defined as systolic blood pressure (sbp) ≥140 mmhg or diastolic blood pressure (dbp) ≥ 90 mmhg]
severely impaired lung function
active gastrointestinal tract ulceration
acute or chronic uncontrolled liver disease, or severe renal disease
uncontrolled diabetes
known history of human immunodeficiency virus (hiv) infection, or active viral infection (hepatitis b virus (hbv), hepatitis c virus (hcv)) at the time of study entry and/or requiring anti-viral therapy, or chronic hepatitis b or c. detection of hepatitis c rna must be performed before inclusion of patients with a history of hcv infection: patients with a positive result are excluded.
history of organ allograft or patient taking immunosuppressive treatment.

e15. patient unable or unwilling to discontinue use of prohibited medications for at least 14 days or 5 half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study.

e16. pregnant or breastfeeding women. e17. patients with any medical, psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule or evaluations of the study results.

e18. patient currently treated with drugs that could interfere with study drugs metabolism e19. patients filling at least one of these criteria are excluded. (specific to olaparib)

patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of mds/aml.
patients considered a poor medical risk due to a serious, uncontrolled seizures, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent myocardial infarction, unstable spinal cord compression , superior vena cava syndrome, extensive bilateral lung disease on high-resolution computed tomography (hrct) scan.
previous allogenic bone marrow transplant or double umbilical cord blood transplantation and whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable) are not allowed.
concomitant use of known strong cyp3a inhibitors or moderate cyp3a inhibitors. the required washout period prior to starting olaparib is 2 weeks.
concomitant use of known strong or moderate cyp3a inducers. the required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
patients eligible for olaparib (lynparza®) in its approved indication: monotherapy for the maintenance treatment of adult patients with platinum sensitive relapsed brca mutated (germline and/or somatic) high grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response to platinum based chemotherapy.
patients with the following cancers: breast or stomach or ovarian or small cell lung cancers.
whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable).

e20. for it: patients filling at least one of these criteria are excluded.

patients with lung or urothelial or head and neck cancers or cns tumors or patients who fulfill conditions to receive one of the investigational therapy of the study
current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10mg/day of prednisone, or an equivalent corticosteroid.",1,0,1,0,0,0,18.0,200.0,Other,Pleura,0,0,All
18,18,18,176,NCT02074839,2023-11-02,study of orally administered ag-120 in subjects with advanced hematologic malignancies with an idh1 mutation,"a phase i, multicenter, open-label, dose-escalation and expansion, safety, pharmacokinetic, pharmacodynamic, and clinical activity study of orally administered ag-120 in subjects with advanced hematologic malignancies with an idh1 mutation",,interventional,"the purpose of this phase i, multicenter study is to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of ag-120 in advanced hematologic malignancies that harbor an idh1 mutation. the first portion of the study is a dose escalation phase where cohorts of patients will receive ascending oral doses of ag-120 to determine maximum tolerated dose (mtd) and/or the recommended phase ii dose. the second portion of the study is a dose expansion phase where four cohorts of patients will receive ag-120 to further evaluate the safety, tolerability, and clinical activity of the recommended phase ii dose. additionally, the study includes a substudy evaluating the safety and tolerability, clinical activity, pharmacokinetics, and pharmacodynamics of ag-120 in subjects with relapsed or refractory myelodysplastic syndrome with an idh1 mutation. anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.","key inclusion criteria:

subject must be ≥18 years of age.
subjects must have documented idh1 r132 gene-mutated advanced hematologic malignancy based on local or central evaluation.
subjects must be amenable to serial bone marrow biopsies, peripheral blood sampling, and urine sampling during the study.
subjects must have ecog ps of 0 to 2.
platelet count ≥20,000/µl (transfusions to achieve this level are allowed).
subjects must have adequate hepatic function as evidenced by: aspartate aminotransferase (ast), alanine aminotransferase (alt), and alkaline phosphatase (alp) ≤3.0 × uln, unless considered due to leukemic disease and serum total bilirubin ≤1.5 x upper limit of normal (uln), unless considered due to gilbert's disease or leukemic disease
subjects must have adequate renal function as evidenced by a serum creatinine ≤2.0 × uln or creatinine clearance >40ml/min based on cockroft-gault glomerular filtration rate (gfr)
subjects must be recovered from any clinically relevant toxic effects of any prior surgery, radiotherapy, or other therapy intended for the treatment of cancer.
female subjects with reproductive potential must have a negative serum pregnancy test within 7 days prior to the start of therapy and on the first day of study drug administration.

key exclusion criteria:

subjects who have undergone hematopoietic stem cell transplant (hsct) within 60 days of the first dose of ag-120, or subjects on immunosuppressive therapy post hsct at the time of screening, or with clinically significant graft-versus-host disease (gvhd). (the use of a stable dose of oral steroids post hsct and/or topical for ongoing skin gvhd is permitted.)
subjects who received systemic anticancer therapy or radiotherapy <14 days prior to their first day of study drug administration. (hydroxyurea is allowed prior to enrollment and after the start of ag-120).
subjects who received an investigational agent <14 days prior to their first day of study drug administration.
subjects who are pregnant or breastfeeding.
subjects with an active severe infection or with an unexplained fever >38.5°c during screening visits or on their first day of study drug administration (at the discretion of the investigator, subjects with tumor fever may be enrolled).
subjects with new york heart association (nyha) class iii or iv congestive heart failure or lvef <40% by echocardiogram (echo) or multi-gated acquisition (muga) scan within approximately 28 days of c1d1.
subjects with a history of myocardial infarction within the last 6 months of screening.
subjects with a known unstable or uncontrolled angina pectoris.
subjects with a known history of severe and/or uncontrolled ventricular arrhythmias.
subjects with known unstable or uncontrolled angina pectoris.
subjects with heart-rate corrected qt (qtc) interval ≥450 ms or other factors that increase the risk of qt prolongation or arrhythmic events.
patients taking medications that are known to prolong the qt interval
subjects with known infection with human immunodeficiency virus (hiv) or active hepatitis b or c.
subjects with clinical symptoms suggesting active central nervous system (cns) leukemia or known cns leukemia. evaluation of cerebrospinal fluid is only required if there is a clinical suspicion of cns involvement by leukemia during screening.
subjects with immediately life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation.",1,1,0,0,0,0,18.0,200.0,Pleura,Pleura,0,0,All
19,19,19,208,NCT02215265,2023-07-19,post-operative adjuvant treatment for hpv-positive tumours (pathos),"a phase iii trial of risk-stratified, reduced intensity adjuvant treatment in patients undergoing transoral surgery for human papillomavirus (hpv)-positive oropharyngeal cancer",PATHOS,interventional,"the main objectives of the pathos study are:

to assess whether swallowing function can be improved following transoral resection of hpv-positive opscc, by reducing the intensity of adjuvant treatment protocols. the aim is to personalise treatment, based on disease biology (hpv status and pathology findings), to optimise patient outcomes.

to demonstrate the non-inferiority of reducing the intensity of adjuvant treatment protocols in terms of overall survival in the reduced intensity treatment arms.","inclusion criteria:

histologically confirmed or suspected squamous cell carcinoma of the oropharynx.
uicc/ajcc tnm 7th edition stage t1-t3, n0-n2b (or uicc tnm 8th edition stage t1-t3, n0-n1) disease.
multidisciplinary team (mdt) decision to treat with primary transoral resection and neck dissection.
patients considered fit for surgery and adjuvant radiotherapy
aged 18 or over.
written informed consent provided.

exclusion criteria:

known hpv negative squamous cell carcinomas of the head and neck: a negative result for p16 immunohistochemistry automatically excludes a patient from the trial. if initial p16 testing is positive but high risk hpv (hr hpv) in-situ hybridization (ish)/polymerase chain reaction (pcr) does not demonstrate the presence of hr hpv dna, the patient will also be excluded. patients who are p16+ may complete swallowing assessments, excluding videofluoroscopy, and surgery whilst hr hpv dna status is being determined (with recourse to central concordance testing, if appropriate, for uk centres). hpv positivity, as determined by p16 and the demonstration of hr hpv dna is essential before patients undergo videofluoroscopy or randomisation.
t4 and/or t1-t3 tumours where transoral surgery is considered not feasible.
uicc/ajcc tnm 7th edition n2c-n3 nodal disease (or uicc/ajcc tnm 8th edition n2-n3 nodal disease).
patients for whom transoral surgery and neck dissection is not considered the primary treatment modality.
current smokers with clinically staged n2b disease (including smokers up to 6 months before diagnosis), even if hpv-positive. vaping is permitted and should be considered as non-smoking status.
any pre-existing medical condition likely to impair swallowing function and/ or a history of pre-existing swallowing dysfunction prior to index oropharyngeal cancer.
patients with distant metastatic disease as determined by routine pre-operative staging radiological investigations e.g., ct thorax and upper abdomen or pet-ct.
patients with a history of malignancy in the last 5 years, except basal cell carcinoma of the skin or carcinoma in-situ of the cervix.
women who are pregnant or breastfeeding and fertile women who will not be using contraception during the trial.",1,0,0,1,0,0,18.0,200.0,Pleura,Pleura,0,0,All
20,20,20,209,NCT02227251,2023-08-03,selinexor (kpt-330) in patients with relapsed/refractory diffuse large b-cell lymphoma (dlbcl),a phase 2b open-label study of selinexor (kpt-330) in patients with relapsed/refractory diffuse large b-cell lymphoma (dlbcl),,interventional,"a multicenter, open-label phase 2b study of selinexor (kpt-330) in participants with relapsed/refractory (r/r) diffuse large b-cell lymphoma (dlbcl) who have no therapeutic options of demonstrated clinical benefit.","inclusion criteria (parts 1 and 2):

written informed consent in accordance with federal, local, and institutional guidelines. the participant must provide informed consent prior to the first screening procedure.
age greater than or equal to (≥) 18 years.
ecog performance status of less than or equal to (≤) 2.
participants should have estimated life expectancy of greater than (>) 3 months at study entry.
previously treated, pathologically confirmed de novo dlbcl, or dlbcl transformed from previously diagnosed indolent lymphoma (e.g., follicular lymphoma).
participants must have received at least 2 but no more than 5 previous systemic regimens for the treatment of their de novo or transformed dlbcl including (i) at least 1 course of anthracycline-based chemotherapy (unless absolutely contraindicated due to cardiac dysfunction, in which case other active agents such as etoposide, bendamustine, or gemcitabine must have been given) and (ii) at least 1 course of anti-cd20 immunotherapy (e.g., rituximab), unless contraindicated due to severe toxicity. participants who were considered ineligible for standard multi-agent immunochemotherapy must have received at least 2 and no more than 5 prior treatment regimens including at least 1 course of anti-cd20 antibodies and must be approved by the medical monitor. prior stem cell transplantation is allowed; induction, consolidation, stem cell collection, preparative regimen and transplantation ± maintenance are considered a single line of therapy.
female participants of child-bearing potential must have a negative serum pregnancy test at screening and agree to use reliable methods of contraception for 3 months after their last dose of medication. male participants must use a reliable method of contraception if sexually active with a female of child-bearing potential. for both male and female participants, effective methods of contraception must be used throughout the study and for 3 months following the last dose.

part 1 additional inclusion criteria:

for participants whose most recent systemic anti-dlbcl therapy induced a pr or cr, at least 60 days must have elapsed since the end of that therapy. for all other participants, at least 14 weeks (98 days) must have elapsed since the end of their most recent systemic anti-dlbcl therapy. . palliative localized radiation within the therapy-free interval is allowed. non-chemotherapy maintenance will not be considered anti dlbcl therapy, and therefore is allowed during the therapy-free interval.
documented clinical or radiographic evidence of progressive dlbcl prior to dosing.
participants must have measurable disease per the revised criteria for response assessment of lymphoma. lymph nodes should be considered abnormal if the long axis is >1.5 centimeter (cm), regardless of the short axis. if a lymph node has a long axis of 1.1 to 1.5 cm, it should only be considered abnormal if its short axis is >1.0. lymph nodes ≤1.0 by ≤1.0 will not be considered abnormal for relapse or pd.

part 2 additional inclusion criteria:

• at least 3 weeks (21 days) must have elapsed since the end of participant's most recent systemic anti-dlbcl therapy (prior to cycle 1 day 1). palliative localized radiation within the therapy-free interval is allowed.non-chemotherapy maintenance will not be considered anti-dlbcl therapy, and therefore is allowed during the therapy-free interval.

• adequate hematopoietic function: (i) hemoglobin ≥10.0 grams per deciliters (g/dl) within 14 days of starting therapy (participant may receive red blood cell [rbc] transfusion within 14 days).

(ii) absolute neutrophil count ≥1000 cells/millimeter (mm^3) (use of granulocyte growth factors prior to and during the study is acceptable).

(iii) platelet count ≥100,000/mm^3 within 14 days of starting therapy (use of platelet growth factors prior to and during the study is acceptable).

participants must have measurable disease per the revised criteria for response assessment of lymphoma. lymph nodes should be considered abnormal if the long axis is >1.5 cm, regardless of the short axis. extranodal lesion should be considered abnormal if the long axis is >1.0 cm.

exclusion criteria (parts 1 and 2):

participants who are pregnant or lactating.
primary mediastinal (thymic) large b-cell lymphoma (pmbl)
participants must not be eligible for high-dose chemotherapy with autologous stem cell transplantation rescue (investigator must provide detailed documentation for ineligibility).
participants who have not recovered to grade ≤1 clinically significant adverse events, or to their baseline, from their most recent systemic anti-dlbcl therapy.
major surgery within 2 weeks of first dose of study treatment.
participants with active hepatitis b virus (hbv), hepatitis c virus (hcv), or human immunodeficiency virus (hiv) infections.
psychiatric illness or substance use that would prevent the participant from giving informed consent or being compliant with the study procedures.

any of the following laboratory abnormalities:

(i) a circulating lymphocyte count of >50,000/l. (ii) hepatic dysfunction: bilirubin >2.0 times the upper limit of normal (uln) (except participants with gilbert's syndrome: total bilirubin of >3*uln) and alanine aminotransferase (alt) and aspartate aminotransferase (ast) >2.5 times uln. in participants with known liver involvement of their dlbcl, ast and alt >5*uln.

(iii) severe renal dysfunction: estimated creatinine clearance of <30 ml/min, measured in 24-hour urine or calculated using the formula of cockroft and gault [(140-age)*mass (kg)/(72*creatinine mg/dl); multiply by 0.85 if female].

any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the participant's safety.
participants with active graft-versus-host disease after allogeneic stem cell transplantation. at least 4 months must have elapsed since completion of allogeneic stem cell transplantation.
uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals on cycle 1 day 1; however, prophylactic use of these agents is acceptable even if parenteral.
participants unable to swallow tablets, participants with malabsorption syndrome, or any other gastrointestinal disease or gastrointestinal dysfunction that could interfere with absorption of study treatment.

part 1 additional exclusion criteria:

for participants whose most recent systemic anti-dlbcl therapy induced a pr or cr: radiation, chemotherapy, immunotherapy, radio-immunotherapy, or any other anticancer therapy other than glucocorticoids <60 days or <14 weeks prior to cycle 1 day 1.
known central nervous system lymphoma or meningeal involvement.
dlbcl with mucosa-associated lymphoid tissue [malt] lymphoma, composite lymphoma (hodgkin's lymphoma+nhl), or dlbcl transformed from diseases other than indolent nhl.

unstable cardiovascular function:

(i) symptomatic ischemia, or (ii) uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on anti-arrhythmia are excluded; 1st degree atrioventricular block or asymptomatic left anterior fascicular block /right bundle branch block will not be excluded), or (iii) congestive heart failure of new york heart association class ≥3, or (iv) myocardial infarction within 3 months.

participants with a bsa <1.4 m^2 as calculated per dubois 1916 or mosteller 1987.

any of the following laboratory abnormalities:

(i) absolute neutrophil count (anc) <1000 cells/mm^3 or platelet count <75,000/mm^3 during screening and on cycle 1 day 1. use of granulocyte-stimulating factors and platelet growth factors prior to and during the study is acceptable.

(ii) hematopoietic dysfunction: hemoglobin < 10.0 g/dl within 14 days of and including cycle 1 day 1 and/or patients receiving red blood cell (rbc) transfusion within 14 days of and including cycle 1 day 1.

participants who have been committed to an institution by official or judicial order.
participants with dependency on the sponsor, investigator or study site.

part 2 additional exclusion criteria:

participants with active hbv, hvc, or hiv infections. participants with active hbv are allowed if antiviral therapy for hepatitis b has been given for >8 weeks and viral load is <100 international units per milliliters (iu/ml) prior to first dose of study treatment. participants with known history of hcv or found to be hcv antibody positive on screening, are allowed if there is documentation of negative viral load per institutional standard. participants with hiv who have cd4+t-cell counts ≥350 cells/microliter (mcl), negative viral load per institutional standard, and no history of acquired immune deficiency syndrome (aids)-defining opportunistic infections in the last year are allowed.
known active central nervous system lymphoma or meningeal involvement. participants with a history of cns disease treated into remission may be enrolled.
dlbcl with malt lymphoma, composite lymphoma (hodgkin's lymphoma + nhl), dlbcl arising from cll (richter's transformation), or high-grade b-cell lymphoma.
received strong cytochrome p450 3a (cyp3a) inhibitors ≤7 days prior to day 1 dosing or strong cyp3a inducers ≤14 days prior to day 1 dosing.",1,0,1,0,0,0,18.0,200.0,Brain,Pleura,0,0,All
21,21,21,221,NCT02260505,2023-08-29,efficiency of imatinib treatment maintenance or interruption after 3 years of adjuvant treatment in patients with gastrointestinal stromal tumours (gist),a randomized multicenter phase iii trial evaluating the interest of imatinib treatment maintenance or interruption after 3 years of adjuvant treatment in patients with gastrointestinal stromal tumours (gist),ImadGist,interventional,"this is a 2 arms study concerning patients with primary gist who followed an imatinib adjuvant treatment for 3 years after surgery and who have a high risk of recurrence.

in the first arm, patients will continue imatinib treatment for 3 more years, allowing to determine if the continuation of this treatment is efficient for disease control, in terms of disease free survival improvement.

in the second arm, patients will discontinue the imatinib treatment, as standard practice. this arm will allow to determine if the re-introduction of imatinib at relapse is still an efficient treatment for the control of disease.","inclusion criteria:

age ≥ 18 years at the day of consenting to the study
patients must have histologically confirmed diagnosis of localized gist with documented kit (cd117) positivity (by polyclonal dako antibody staining)
documented macroscopically complete surgical r0 or r1 resection of primary gist lesion with no evidence of residual lesions or metastases on the baseline ct-scan or mri performed no more than 4 weeks before randomization.
risk of tumor recurrence ≥ 35% according to national comprehensive cancer network task force on gist (nccn) risk classification (demetri et al., 2010) (see appendix 1)
eastern cooperative oncology group (ecog) performance status 0, 1 or 2
patients must be under imatinib treatment (at 300 or 400 mg/day) initiated immediately after resection and maintained for 3 years (i.e. 36 months ± 3 months at the time of randomization) with no more than 3 consecutive months or 6 months in total of interruption during these past 3 years.

patients must have normal organ and bone marrow function at baseline as defined below:

absolute neutrophil count (anc) ≥ 1.5 g/l, platelet count ≥ 100 g/l, and haemoglobin of ≥ 9 g/dl).
serum total bilirubin ≤ 1.5 (upper limit of normal (uln), aspartate aminotransferase (ast) and alanine aminotransferase (alt) ≤ 3 x uln (or 5 x uln in case of hepatic metastases at time of reintroduction)

adequate renal function assessed by at least one of the following:

1) serum creatinine ≤ 1.5 x uln or
2) creatinine clearance estimate ≥ 50 ml/min (as calculated according to cockcroft-gault formula or mdrd formula for patients > 65 years).
recovered from prior anti-neoplasia treatment-related toxicity (persistent treatment-related toxicity < grade 2 as per common toxicity criteria for adverse effects (ctcae) v4 are accepted)
women of childbearing potential are required to have a negative serum pregnancy test within 72 hours prior to randomization. a positive urine test must be confirmed by a serum pregnancy test
patient must use effective contraception at least 4 weeks prior to study entry, during the study participation and for at least 30 days post-treatment (not applicable for women of non-childbearing potential)
ability to understand and willingness for follow-up visits.
covered by a medical insurance.
signed and dated informed consent document indicating that the patient has been informed of all aspects of the trial prior to enrolment.

exclusion criteria:

pregnant or breastfeeding women
patient concurrently using other approved or investigational antineoplastic agents
any contra-indication to imatinib treatment as per glivec® spc
patient with gist harboring the mutation d842v in pdgfra
major concurrent disease affecting cardiovascular system, liver, kidneys, haematopoietic system or else considered as clinically important by the investigator and that could be incompatible with patient's participation in this trial or would likely interfere with study procedures or results.
prior history of other malignancies other than study disease (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) unless the patient has been free of the disease for at least 3 years.
patient receiving concurrent treatment with warfarin (acceptable alternative: low-molecular weight heparin) or any prohibited concomitant and/or concurrent medications
patient with grade iii/iv cardiac problems as defined by the new york heart association criteria. (i.e., congestive heart failure, myocardial infarction within 6 months of study)
patient has a known diagnosis of human immunodeficiency virus (hiv) infection.
major surgery within 2 weeks prior to study entry",1,0,0,1,0,0,18.0,200.0,Gastric,Gastric,0,0,All
22,22,22,222,NCT02260739,2017-08-07,sequential analysis in patients with an hemopathy,sequential analysis in patients with an hemopathy,S-HEMO,interventional,"recent advances in hematology clearly illustrate that the simple ""clonal"" nature of various hematological malignancies may not really reflect the reality of malignant cells natural expansion. this has been nicely illustrated in recent works in aml for example where subclones coexists in the same patient at the same time, but could also differentially expand over time because of effects of therapeutics intervention, but also by oncogenic spontaneous events (1).

these observations have been done recently because of next generation sequencing that allows to discriminate in the same tumor samples, different subclones and to analyse the clonal architecture. sequential analyses could help us to identify the first oncogenic event and to correlate disease progression to the emergence of subclones.

for all these reasons it is of a major interest to precisely understand the architecture of the clone in mpns, especially to understand which is the initiating event and how from this initial event the clone develops.

in mpns in which jak2v617f is the initiating event, its targeting is expected to be extremely effective. if jak2v617f is a secondary event its targeting might allow to alleviate the mpn, but may favor the development of other malignant hemopathies.","inclusion criteria:

patients with a malignant hematological disease.
signed written informed consent
age and sex : men and women aged 18 years or older
patients affiliated to a social security system

exclusion criteria:

- patients protected by law, in accordance with articles l1121-l1121-5 to 8 of the code of public health.",1,0,0,0,0,1,18.0,200.0,Vulva,Vulva,0,0,All
23,23,23,223,NCT02264678,2023-10-24,ascending doses of ceralasertib in combination with chemotherapy and/or novel anti cancer agents,"a modular phase i, open-label, multicentre study to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumour activity of ceralasertib in combination with cytotoxic chemotherapy and/or dna damage repair/novel anti-cancer agents in patients with advanced solid malignancies.",,interventional,"this is a modular, phase i/ phase 1 b, open-label, multicentre study of ceralasertib administered orally in combination with cytotoxic chemotherapy regimens and/or novel anti-cancer agents, to patients with advanced malignancies. the study design allows an investigation of optimal combination dose of ceralasertib with other anti-cancer treatments, with intensive safety monitoring to ensure the safety of the patients. the initial combination to be investigated is ceralasertib with carboplatin. the second combination to be investigated is ceralasertib with olaparib. the third combination to be investigated is ceralasertib with durvalumab. the fourth module will investigate the effect of food on ceralasertib absorption and the effect of ceralasertib on ecg parameter. the fifth module to be investigated is ceralasertib with azd5305.","principal inclusion criteria:

aged at least 18
the presence of a solid malignant tumour that is not considered appropriate for further standard treatment
module 2 part b study expansions, and module 3: patients must have a tumour at least 1 cm in size that can be measured using a ct or mri scan
module 2 part b all (except b5): no previous treatment with parp inhibitor.
module 2 part b1 study expansion: advanced gastric adenocarcinoma (including gej) patients with atm deficient tumours
module 2 part b2 study expansion: advanced gastric adenocarcinoma (including gej) patients with atm proficient tumours
module 2 part b3 study expansion: second or thrid line her2 negative breast cancer
module 2 part b4 study expansion: second or third line triple negative breast cancer (tnbc)
module 2 part b5 study expansion: brcam or rad51c/dm or palb2m or hrd positive status ovarian cancer patient who are platinum sensitive relapsed and have previously progressed on a licensed parpi
module 3: advanced recurrent or metastatic non-small cell lung cancer, or head and neck squamous cell carcinoma
module 4: any advanced solid tumours except gastric, gastro-oesophageal, oesophageal or colorectal cancer with a small bowel resection
module 4: ability to comply with an overnight fast of at least 10 hours prior to dosing and 4 hours after dosing as mandated, and ability to eat a high fat meal as mandated
module 5 all: ovarian fallopian tube or primary peritonial cancer, previous treatment with parp inhibitor, platinum-sensitive relapsed ovarian cancer
module 5 part b: known or suspected brca mutation, palb2 mutation, rad51c/d mutation or hrd positive status

principal exclusion criteria

a diagnosis of ataxia telangiectasia
prior exposure to an atr inhibitor
bad reaction to ceralasertib
module 2: contra-indicated for treatment with olaparib
module 3: contra-indicated for treatment with durvalumab
module 4: mean resting corrected qt interval (qtc) >470 msec or history of familial long qt syndrome.
module 4: patients with type i or type ii diabetes
module 5: known hypersensitivity to parp including azd5305",1,1,1,0,0,0,18.0,130.0,Pleura,Other,0,0,All
24,24,24,225,NCT02266745,2023-08-10,"a study evaluating the safety, pharmacokinetics, and clinical effects of intravenously administered pt-112 injection in subjects with advanced solid tumors and subsequent dose expansion cohorts","a phase 1, open-label, dose-escalation study evaluating the safety, pharmacokinetics, and clinical effects of intravenously administered pt-112 injection in subjects with advanced solid tumors and subsequent dose expansion cohorts",,interventional,"this is a phase 1/2, open-label, multi-center, non-randomized, dose-escalation study to be conducted in two parts: the dose escalation phase and the dose expansion phase. the dose escalation phase will determine the maximum tolerated dose (mtd) and recommended phase 2 dose(s) (rp2d) of pt-112 injection and evaluate its safety and tolerability, and pk (pharmacokinetics).

the dose escalation phase is complete and no longer enrolling.

the dose expansion phase has two cohorts: one cohort for the study of pt-112 in patients with thymoma and thymic carcinoma (cohort a), and one cohort for the study of pt-112 in metastatic castrate-resistant prostate cancer (mcrpc) (cohort d).","key inclusion criteria:

male >/= 18 years of age
histologically or cytologically confirmed adenocarcinoma of the prostate.
document current evidence of metastatic castration-resistant prostate cancer (mcrpc), where metastatic status is defined as having documented metastatic lesion(s) on either bone scan or ct/mri scan.
patients who have received at least three prior intended life-prolonging therapies for metastatic disease.
eastern collaborative oncology group (ecog) performance status of 0-1.
progressive disease, either measurable on physical examination or imaging by response evaluation criteria in solid tumors (recist v1.1) or pcwg3 or by informative tumor marker(s).
adequate organ function based on laboratory values.
if there is a known history of brain metastases, either treated or untreated, the disease must be stable.

key exclusion criteria:

any cytotoxic chemotherapy within 21 days prior to initiation of study drug.
any immunomodulatory drug therapy, anti-neoplastic hormonal therapy, immunosuppressive therapy, corticosteroids, or growth factor treatment within 14 days prior to initiation of study drug.
bone marrow reserve which is not adequate for participation in this trial.
radiotherapy within 14 days prior to baseline.
fraction of radiotherapy to >25 % of active bone marrow.
major surgery within 28 days prior to initiation of study drug.",1,0,1,0,0,0,18.0,200.0,Pleura,Pleura,1,0,Male
25,25,25,229,NCT02275286,2023-05-29,trabectedin plus radiotherapy in soft tissue sarcoma patients,"phase i-ii prospective trial, multicenter, open label, exploring the combination of trabectedin plus radiotherapy in soft tissue sarcoma patients",TRASTS,interventional,"phase i-ii trial that combines trabectedin plus radiotherapy for tumor reduction response measure in four cohorts of patients:

cohort a: patients with diagnosis of non-operable or unresectable or not oncologically recommended metastasectomy of limited to lung metastases soft tissue sarcoma.

cohort b: patients with locally advanced resectable myxoid liposarcoma. cohort c: patients with retroperitoneal and resectable soft tissue sarcoma (liposarcoma and leiomyosarcoma).

cohort d (phase ii only): patients with well differentiated liposarcoma and g2 dedifferentiated liposarcoma (with less than 30% dedifferentiated component).

phase i: escalating dose of 1.3 or 1.5 mg/m2. phase i for cohort c: de-escalating dose of 1.5 or 1.3mg/m2 radiotherapy for cohort a: 30gy in 10 fractions (3gy/fraction). radiotherapy for cohort b: 45gy in 25 fractions (1.8gy/fraction). radiotherapy for cohort c: 45gy in 25 fractions (1.8gy/fraction).

radiotherapy for cohort d: 45gy in 25 fractions (1.8gy/fraction). a translational substudy is developed to analyse different biomarkers predictive value.

cohorts a and b are closed to recruitment in 2023.","cohort a: sts

inclusion criteria:

the patient must sign voluntarily the informed consent form before any study test is conducted that is not part of routine patient care.
aged equal or over 18.
patients must have a diagnostic of soft tissue sarcoma with metastasis limited to lung, and not suitable for metastasectomy or surgery resection or not oncologically recommended metastasectomy.a centralized diagnostic will be performed, the tumor sample must be available and sent prior to inclusion.
disease distribution allows meeting with normal tissue constraints of radiation therapy. radiation oncologist must confirm this point.
metastatic spread could be present in two organs at maximum (i.e. lungs and pelvic fosa).
those lesions considered for radiation therapy have to be considered as target lesions as well. (i.e. in a patient with nodules in lungs, those lesions selected for radiation therapy have to include at least the target lesions)
it is allowed that not all the lesions will be under radiation fields. as a general rule, it will be prioritized to select, as target-irradiating lesions, those with greater increase in size and those largest lesions. it should be discouraged to irradiate pulmonary lesions with infiltration of pleural serosa.
patients must have documentation of disease progression within 6 months prior to study entry.
the patient must have been considered eligible for systemic chemotherapy. a maximum of two previous lines for advanced/metastatic disease are allowed as long as trabectedin has not been included.

the following histological subtypes can be included:

undifferentiated pleomorphic sarcoma (previously, malignant fibrous histiocytoma) leiomyosarcoma angiosarcoma/ epithelial hemangioendothelioma liposarcoma and its variants (well differentiated, dedifferentiated, myxoid/round cells, pleomorphic).

synovial sarcoma fibrosarcoma and its variants (epithelial fibrosarcoma/low grade fibromyxoid sarcoma) hemangiopericytoma/solitary fibroid tumor neurogenic sarcoma (malignant peripheral nerve sheath tumor, mpnst) myxofibrosarcoma epithelioid sarcoma unclassified sarcoma (spindle cell/epithelioid/pleomorphic/myxoid)

measurable disease, according to recist v 1.1 criteria
performance status ≤1 (ecog).
adequate respiratory functions: fev1 >1l; dlco > 40% (patients with pulmonary target lesions)
adequate bone marrow function (hemoglobin > 10 g/dl, leukocytes ≥ 3.000/mm3, neutrophils ≥ 1.500/mm3, platelets ≥ 100.000/mm3). patients with plasma creatinine ≤ 1,6 mg/dl, transaminases ≤ 2.5 times the unl, total bilirubin ≤ unl, cpk ≤ 2.5 times unl, alkaline phosphatase ≤ 2.5 times the unl are acceptable. if the increase of alkaline phosphatase is > 2.5 times the unl, then the alkaline phosphatase liver fraction and/or ggt must be ≤ unl.
men or women of child bearing potential should be using an effective method of contraception before entry into the study and throughout the same and for 6 months after ending the study. women of childbearing potential must have a negative urine pregnancy test before study entry.
normal cardiac function with a lvef ≥ 50% by echocardiogram or muga.
it should be performed hbv and hcv serologies prior to inclusion. if hbsag is positive it is recommended to reject the existence of replicative phase (hbaag+, dna vhb+). if these were positives the inclusion is not recommended, remaining at investigators' discretion the preventive treatment with lamivudine. if a potential patient is positive for anti-hcv antibodies, presence of the virus should be ruled out with a qualitative pcr, or the patient should not be included in the study (if a qualitative pcr cannot be performed then patient will not be able to enter the study)
patient must have a central venous catheter for treatment

exclusion criteria:

previous treatment with trabectedin or previous treatment with radiotherapy (except if previous radiotherapy treatment plus planned study radiotherapy treatment allow tissues constrains)
performance status ≥ 2 (ecog).
plasma bilirubin > unl.
creatinine > 1.6 mg/dl.
history of other neoplastic disease with less than 5 years free of disease with the exception of basal cell carcinoma or in situ cervical cancer adequately treated.
severe copd or other severe pulmonary diseases.
significant cardiovascular disease (for example, dyspnea > 2 nyha)
significant systemic diseases grade 3 or higher on the nci-ctcae v4.03 scale, that limit patient availability, or according to investigator judgment may contribute significantly to treatment toxicity.
uncontrolled bacterial, mycotic or viral infections.
known positive test for infection by human immunodeficiency virus (hiv).
women who are pregnant or breast-feeding.
psychological, familial, social or geographic circumstances that limit the patient""s ability to comply with the protocol or informed consent.
patients participating in another clinical trial or receiving any other investigational product
patients who had participated in another clinical trial and/or had received any other investigational product in the last 30 days prior to inclusion.
histologies other than those described in inclusion criteria.

cohort b: ml

inclusion criteria:

the patient must sign voluntarily the informed consent form before any study test is conducted that is not part of routine patient care.
age ≥18 years old.
pathological diagnosis of myxoid liposarcoma, deep located and more than 5 cm or superficial more than 10 cm. a centralized diagnostic will be performed to confirm that the patient can be included in the study.
tumor must be resectable and without evidence of regional or distal spread after adequate staging procedure. tumor must be located in limbs or superficial trunk wall.
disease distribution allows meeting with normal tissue constraints of radiation therapy. radiation oncologist must confirm this point.
measurable disease, according to recist v 1.1 criteria
performance status 0-1 (ecog).
adequate bone marrow function (hemoglobin > 10 g/dl, leukocytes ≥ 3.000/mm3, neutrophils ≥ 1.500/mm3, platelets ≥ 100.000/mm3). patients with plasma creatinine ≤ 1,6 mg/dl, transaminases ≤ 2.5 times the unl, total bilirubin ≤ unl, cpk ≤ 2.5 times unl, alkaline phosphatase ≤ 2.5 times the unl are acceptable. if the increase of alkaline phosphatase is > 2.5 times the unl, then the alkaline phosphatase liver fraction and/or ggt must be ≤ unl.
men or women of child bearing potential should be using an effective method of contraception before entry into the study and throughout the same and for 6 months after ending the study. women of childbearing potential must have a negative urine pregnancy test before study entry.
normal cardiac function with a lvef ≥ 50% by echocardiogram or muga.
it should be performed hbv and hcv serologies prior to inclusion. if hbsag is positive it is recommended to reject the existence of replicative phase (hbaag+, dna hbv+). if these were positives the inclusion is not recommended, remaining at investigators' discretion the preventive treatment with lamivudine. if a potential patient is positive for anti-hcv antibodies, presence of the virus should be ruled out with a qualitative pcr, or the patient should not be included in the study (if a qualitative pcr cannot be performed then patient will not be able to enter the study).
patient may have had one previous chemotherapy line.
patient must have a central venous catheter for treatment.

exclusion criteria:

unresectable tumors (with limb sparing surgery)
more than one previous chemotherapy treatment for local disease including trabectedin.
radiotherapy involving the tumoral bed.
performance status ≥ 2 (ecog).
presence of metastases or lymph node involvement by the tumor.
location other than limb or superficial trunk wall.
plasma bilirubin > unl.
creatinine > 1.6 mg/dl.
history of other neoplastic disease with less than 5 years free of disease with the exception of basal cell carcinoma or in situ cervical cancer adequately treated.
significant cardiovascular disease (for example, dyspnea > 2 nyha)
significant systemic diseases grade 3 or higher on the nci-ctcae v4.03 scale, that limit patient availability, or according to investigator judgment may contribute significantly to treatment toxicity.
uncontrolled bacterial, mycotic or viral infections.
known positive test for infection by human immunodeficiency virus (hiv).
women who are pregnant or breast-feeding.
psychological, familial, social or geographic circumstances that limit the patient""s ability to comply with the protocol or informed consent.
patients who had participated in another clinical trial and/or had received any other investigational product in the last 30 days prior to inclusion.

cohorts c and d: retroperitoneum sarcoma

inclusion criteria:

the patient must voluntarily sign the informed consent form before performing any study-specific test that is not part of the patient's usual care.
aged between 18 and 75 years.

the following histological subtypes may be included in the cohort c:

high grade leiomyosarcoma (g2-3), liposarcoma (g2-3), if at least 30% of the tumour is dedifferentiated, pleomorphic liposarcoma.

the following histological subtypes may be included in the cohort d:

well differentiated liposarcoma (wd liposarcoma) and g2 dedifferentiated liposarcorcoma, if less than 30% of the tumour is dedifferentiated.

a centralised diagnosis will be made to confirm that the patient can be included in the study.

the tumour must be located in the retroperitoneum and it must be resectable and without evidence of regional or distal spread after the appropriate staging process. this point must be confirmed by the central surgeon reviewer.
the location and size of the disease in the retroperitoneum must allow for compliance with radiotherapy limitations in healthy tissue. this point must be confirmed by the site's radiation oncologist and the central radiation oncologist reviewer.
measurable disease according to choi criteria for cohort c and recist v 1.1 criteria for cohort d.
ecog performance status 0-1.
adequate haematological parameters (haemoglobin >10 g/dl, leukocytes ≥3,000/mm3, neutrophils ≥1,500/mm3, platelets ≥100,000/mm3). patients with plasma creatinine ≤1.6 mg/dl, transaminases ≤2.5 times the uln, total bilirubin ≤ uln, cpk ≤2.5 times uln, alkaline phosphatase ≤2.5 times uln are acceptable. if the increase in alkaline phosphatase is >2.5 times the uln, the liver fraction of alkaline phosphatase and/or ggt should be ≤uln.
fertile men or women must use an effective contraceptive method before starting the study, during the study and for 6 months following the conclusion thereof. women of childbearing potential who participate in the study must undergo a pregnancy test before starting the study.
normal cardiac function with lvef ≥50% by echocardiogram or muga.
hbv and hcv serology must be performed before including the patient in the study. if hbsag is positive, it is advisable to rule out a replicative phase (hbsag*, dna hbv+). if positive, the patient's inclusion in the trial is not recommended, and it is at the discretion of the investigator to administer preventive treatment with lamivudine. if a potential patient is positive to anti-hcv antibodies, the presence of the virus will be ruled out with a qualitative pcr, or the patient cannot be included in the study (if the qualitative pcr test cannot be performed on the patient, they cannot be included in the study).
patient may have had one previous chemotherapy line (cohort d only).
the patient must have a central venous catheter for the administration of the treatment.

exclusion criteria

unresectable tumours.
location other than the retroperitoneum.
patients who have previously received systemic treatment with chemotherapy (trabectedin included). for cohort d, patients may have received one previous line of chemotherapy with any other agent.
patients who underwent prior local treatment for retroperitoneal sarcoma: surgery or radiotherapy in the tumour bed.
ecog performance status ≥2.
presence of metastasis or lymph node involvement of the tumour.
previous history of another neoplastic disease with less than 5 years free of disease except for basal cell carcinoma or properly treated in situ cervical cancer.
significant cardiovascular disease (e.g. dyspnoea >2 nyha).
a significant grade 3 or greater systemic disease on the nci-ctcae v4.03 scale, which may limit the availability of the patient or which, in the opinion of the investigator, may contribute to the toxicity caused by the study treatment.
uncontrolled viral, mycotic or bacterial infections.
known hiv-positive patients.
pregnant or breast-feeding women.
psychological, familial, social or geographical circumstances that limit the patient's ability to comply with the protocol or informed consent form.
patients who have participated in another clinical trial and/or have received another investigational product in the 30 days prior to inclusion in the trial.",1,1,1,0,0,0,18.0,200.0,Pleura,Pleura,0,0,All
26,26,26,243,NCT02303821,2023-10-18,study of carfilzomib in combination with induction chemotherapy in children with relapsed or refractory acute lymphoblastic leukemia,phase 1b/2 study of carfilzomib in combination with induction chemotherapy in children with relapsed or refractory acute lymphoblastic leukemia,,interventional,"the purpose of phase 1b of this study is to:

asses the safety, tolerability and activity of carfilzomib, alone and in combination with induction chemotherapy, in children with relapsed or refractory acute lymphoblastic leukemia (all).
determine the maximum tolerated dose (mtd) and to recommend a phase 2 dose of carfilzomib in combination with induction chemotherapy.

the purpose of phase 2 of this study is to compare the rate of complete remission (cr) of carfilzomib in combination with vincristine, dexamethasone, peg asparaginase, daunorubicin (vxld) at the end of induction therapy to an appropriate external control.","phase 1b key inclusion criteria:

age 21 years or younger at the time of initial all diagnosis and age > 1 year at the time of study treatment initiation.

subjects must have a diagnosis of relapsed or refractory all with ≥ 5% blasts in the bone marrow (m2 or m3 disease), with or without extramedullary disease.

-to be eligible, subjects must have had 1 or more prior therapeutic attempts, defined as:

early first relapse (< 36 months from original diagnosis) after achieving a cr (b-all) or first relapse any time following the original diagnosis after achieving a cr (t-all)
first refractory bone marrow relapse occurring any time after original diagnosis after achieving a cr (ie, ≥1 failed attempt to induce a second remission) or
relapse after achieving a cr following the first or subsequent relapse (i.e., ≥ 2 relapses) or
failing to achieve a cr from original diagnosis after at least 1 induction attempt
subjects must have fully recovered from the acute toxic effects of all previous chemotherapy, immunotherapy, or radiotherapy treatment before enrollment.
subjects must have a serum creatinine level that is ≤ 1.5 × institutional upper limit of normal (uln) according to age. if serum creatinine level is > 1.5 × uln, the subject must have a calculated creatinine clearance or radioisotope glomerular filtration rate (gfr) ≥ 70 ml/min/1.73 m2.

adequate liver function, defined as both of the following:

total bilirubin ≤ 1.5 × institutional uln except in the presence of gilbert syndrome
alanine aminotransferase (alt) ≤ 5 × institutional uln
performance status: karnofsky or lansky scores ≥ 50 for subjects > 16 years old or ≤ 16 years old, respectively.

phase 2 inclusion criteria:

subject's legally acceptable representative has provided informed consent when the subject is legally too young to provide informed consent and the subject has provided written assent based on local regulations and/or guidelines prior to any study-specific activities/procedures being initiated, except for standard of care local testing as permitted per protocol.
age greater than or equal to 1 month to less than 21 years. subjects greater than or equal to 18 years must have had their original diagnosis at less than 18 years of age.
subjects must be diagnosed with relapsed or refractory relapsed all.
subjects must have a documented first remission, less than 5% blasts in the bone marrow (m1 bone marrow) and no evidence of extramedullary disease.

t-cell all with bone marrow relapse (defined as greater than or equal to 5% leukemia blasts in bone marrow) or refractory relapse with or without extramedullary disease.

or b-cell all bone marrow relapse or refractory relapse (defined as greater than or equal to 5% leukemia blasts in bone marrow) after having received a targeted b-cell immune therapy (eg, blinatumomab, inotuzumab or a car-t therapy) with or without extramedullary disease..

adequate liver function: bilirubin less than or equal to 1.5 x upper limit of normal (uln), alanine aminotransferase (alt) less than or equal to 5 x uln.
adequate renal function: serum creatinine less than or equal to 1.5 x uln or glomerular filtration rate (gfr) greater than or equal to 70 ml/min/1.73 m^2; or for children less than 2 years of age, greater than or equal to 50 ml/min/1.73 m^2.
adequate cardiac function: shortening fraction greater than or equal to 30% or ejection fraction greater than or equal to 50%.
karnofsky (subjects greater than or equal to 16 years of age) or lansky (subjects 12 months to less than 16 years of age) performance status greater than or equal to 50%.
subjects must have fully recovered from the acute toxic effects of all previous chemotherapy, immunotherapy, or radiotherapy treatment before enrollment (for example: recovery from gastrointestinal toxicity may occur more rapidly than less reversible organ toxicities such as sinusoidal obstruction syndrome or non-infectious pneumonitis, for serious prior toxicities recommended discussion with amgen medical monitor).
life expectancy of greater than 6 weeks per investigator's judgement at time of screening.

phase 1b key exclusion criteria:

known allergy to any of the drugs used in the study (subjects who have had a previous allergy to peg-asparaginase and if able, may receive erwinia asparaginase at the investigator's discretion)
known allergy to captisol (a cyclodextrin derivative used to solubilize carfilzomib)
left ventricular fractional shortening < 30%
history of ≥ grade 2 pancreatitis
active graft-versus-host disease requiring systemic treatment
positive culture for or other clinical evidence of infection with bacteria or fungus within 14 days of the initiation of study treatment
down syndrome

prior therapy restrictions:

subjects must have completed therapy with granulocyte-colony stimulating factor (g-csf) or other myeloid growth factors at least 7 days before study treatment initiation, or at least 14 days before study treatment initiation, if pegylated myeloid growth factors were administered.
subjects must have completed any type of active immunotherapy (e.g., tumor vaccines) at least 42 days before study treatment initiation.
subjects must have received the last dose of a non-monoclonal antibody biologic agent at least 7 days before study treatment initiation.
at least 3 antibody half-lives must have elapsed since the last dose of monoclonal antibody (e.g., 66 days for rituximab and 69 days for epratuzumab) before subjects may initiate study treatment.
subjects must not have received other antineoplastic agents with therapeutic intent, excluding hydroxyurea and antimetabolites administered as part of maintenance chemotherapy, within 7 days prior to study treatment initiation.
hepatitis b infection with positive hepatitis b dna

phase 2 exclusion criteria:

prior treatment with carfilzomib.
intolerance, hypersensitivity, or inability to receive any of the chemotherapy components of the vxld regimen. an exception is allowed for allergy to asparaginase products if erwinia asparaginase is unable to be administered,
autologous hsct within 6 weeks prior to start of study treatment.
allogeneic hsct within 3 months prior to start of study treatment.
active gvhd requiring systemic immune suppression.
less than 30 days from discontinuation of immune suppressive therapy administered for the treatment of acute or chronic gvhd.
isolated extramedullary relapse.
positive bacterial or fungal infection within 14 days of enrollment (except for documented line infection, line has been removed, and blood culture after line removal is negative for 5 days prior to first dose of induction therapy). antibiotics may be administered for prophylaxis as per institutional standards up to and after enrollment.
subjects with less than 3 antibody half-lives since the last dose of monoclonal antibody (eg, 66 days for rituximab, 69 days for epratuzumab, inotuzumab for 36 days), prior to first dose of investigational product must be discussed with the amgen medical monitor and may be allowed to enroll based on extent of disease or evidence of rapidly rising peripheral or bone marrow blast counts.
cell-based immunotherapy (eg, donor leucocyte infusion, car-t cells, tumor vaccines) within 42 days prior to first dose of investigational product. if the amgen medical monitor agrees, an exception may be granted to the 42-day requirement for subjects with rapidly rising peripheral or bone marrow blast counts.
down's syndrome.
presence of another active cancer.
history of grade greater than or equal to 2 pancreatitis within 6 months to screening.
unresolved toxicities from prior anticancer therapy, defined as not having resolved to ctcae version 4.03 grade 1 or to levels dictated in the eligibility criteria apart from alopecia or toxicities from prior anticancer therapy that are considered irreversible and do not trigger another exclusion criterion (defined as having been present and stable for greater than 4 weeks).
antitumor therapy (chemotherapy, investigational agents, molecular-targeted therapy) within 7 days of day 1 of induction. exception: hydroxyurea to control peripheral blood leukemic cell counts is allowed until start of investigational product.
active viral infection, including but not limited to cytomegalovirus (cmv), hepatitis b infection with positive serum hepatitis surface antigen or hepatitis b dna, hiv, hepatitis c with detectable hepatitis c rna. subjects who have previously received a stem cell transplant must be screened for cmv infection, unless both subject and donor are known to be cmv negative.
currently receiving treatment in another investigational device or product study, or less than 14 days since ending treatment on another investigational device or product study.
uncontrolled arrhythmias or screening ecg with corrected qt interval (qtc) of greater than 470 msec.
history or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 6 months after the last dose of any study treatment or for 12 months after last dose of cyclophosphamide if administered during optional consolidation cycle.
female subjects of childbearing potential unwilling to use 1 highly effective method of contraception during treatment and for an additional 6 months after the last dose of any study treatment or for 12 months after last dose of cyclophosphamide if administered during optional consolidation cycle.
female subjects of childbearing potential with a positive pregnancy test assessed at screening by a serum or urine pregnancy test.
male subjects with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use a condom with spermicide during treatment and for an additional 6 months after the last dose of any study treatment, even if they have undergone a successful vasectomy.
male subjects with a pregnant partner who are unwilling to practice abstinence or use a condom with spermicide during treatment, for duration of pregnancy, and for an additional 6 months after the last dose of any study treatment.
male subjects unwilling to abstain from donating semen or sperm during treatment and for an additional 6 months after the last dose of any study treatment.
known allergy to captisol (a cyclodextrin derivative used to solubilize carfilzomib; for a complete listing of captisol-enabled drugs, see the ligand pharmaceuticals, inc. website).",1,1,0,0,0,0,0.0833333333333333,21.0,Pleura,Pleura,0,0,All
27,27,27,255,NCT02320656,2018-07-24,"predictive clinical and biological parameters in acute leukemia, myelodysplastic syndromes and myeloproliferative disorders-hemato-bio-ipc-2013-015","predictive clinical and biological parameters in acute leukemia, myelodysplastic syndromes and myeloproliferative disorders-hemato-bio-ipc-2013-015",HEMATO-BIO,interventional,"hemato-bio-ipc-2013-015 is a monocenter prospective longitudinal study. our aim is to define predictive clinical and biological factors in acute leukemia, myelodysplastic syndromes and myeloproliferative disorders by using genomics, genetics and epigenetics, in vitro and in vivo drug sensitivity studies,and translational immonulogy and immunomonitoring studies.

hemato-bio primary outcome measure is to identify molecular, genomic and epigenetic, pharmacologic and immunophenotypic alteration in acute leukemia, myelodysplastic syndromes and myeloproliferative disorders by collecting, at diagnosis and/or complete remission and/or relapse:

tumor samples: marrow aspiration, blood sampling.
non-tumor samples: skin biopsy, buccal swab . from 650 patients treated at our cancer center.","inclusion criteria:

acute leukemia, myelodysplastic syndrome or myeloproliferative disease
age > 18
affiliated to the french social security systm
signed informed consent

exclusion criteria:

emergency
patients deprived of liberty or placed under the authority of a tutor",1,0,0,0,0,1,18.0,200.0,Pleura,Pleura,0,0,All
28,28,28,257,NCT02331498,2023-02-13,phase i/ii study of pazopanib+ temozolomide in patients with newly diagnosed glioblastoma multiforme,a phase i/ii study of pazopanib in combination with temozolomide in patients with newly diagnosed glioblastoma multiforme after surgery and rt-ct,PAZOGLIO,interventional,a phase i/ii study of pazopanib in combination with temozolomide in patients with newly diagnosed glioblastoma multiforme after surgery and rt-ct (pazoglio study),"inclusion criteria:

subjects must provide written informed consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow up.
age ≥ 18 years and < 70 years
histologically confirmed diagnosis of gbm
surgically treated other than exclusive biopsy (complete or partial resection) of the gbm, for which adjuvant radiotherapy and chemotherapy is indicated
eligibility criteria that will need to be checked before patient registration and - no tmz interruption resulting in hematological toxicity should has occurred
and the delivery of radiation dose as defined in the stupp protocol should be at least equal to 80%
eastern cooperative oncology group (ecog) performance status of glioblastoma ≤ 2
life expectancy>3 months
measurable disease criteria : based on the rano criteria (wen 2010) objective tumor response will be assessed by mri and 18f-dopa pet)
archived tumor tissue must be available for all subjects for biomarker analysis before and/or during treatment with investigational product.
stable doses of corticosteroid for more than 1 week.
adequate biological function
women of childbearing potential must have a negative serum pregnancy test within 14 days of first dose of study treatment and agree to use effective contraception, as defined in pregnancy section in overall safety section during the study and for 6 months following the last dose of investigational product.

exclusion criteria:

prior malignancy.
surgical treatment consisting in exclusive biopsy or absence of initial surgery
pre-treated gbm
allergy to any of the tested drugs
clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including,
clinically significant gastrointestinal abnormalities that may affect absorption of investigational product
corrected qt interval (qtc) > 480 msecs
history of any one or more of ardiovascular conditions within the past 6 months
poorly controlled hypertension
history of cerebrovascular accident including transient ischemic attack (tia), pulmonary embolism or untreated deep venous thrombosis (dvt) within the past 6 months.
major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major surgery).
evidence of active bleeding or bleeding diathesis.
known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage
recent hemoptysis
any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
unable or unwilling to discontinue use of prohibited medications listed in appendix c for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study (appendix c).

treatment with any of the following anti-cancer therapies:

radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazoapnib or
chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib
administration of any non-oncologic investigational drug within 30 days or 5 half-lives whichever is longer prior to receiving the first dose of study treatment
any ongoing toxicity from prior anti-cancer therapy that is >grade 1 and/or that is progressing in severity, except alopecia.",1,1,1,0,0,0,18.0,70.0,Brain,Brain,0,0,All
29,29,29,258,NCT02332668,2023-10-26,a study of pembrolizumab (mk-3475) in pediatric participants with an advanced solid tumor or lymphoma (mk-3475-051/keynote-051),"a phase i/ii study of pembrolizumab (mk-3475) in children with advanced melanoma or a pd-l1 positive advanced, relapsed or refractory solid tumor or lymphoma (keynote-051)",,interventional,"this is a two-part study of pembrolizumab (mk-3475) in pediatric participants who have any of the following types of cancer:

advanced melanoma (6 months to <18 years of age),
advanced, relapsed or refractory programmed death-ligand 1 (pd-l1)-positive malignant solid tumor or other lymphoma (6 months to <18 years of age),
relapsed or refractory classical hodgkin lymphoma (rrchl) (3 years to <18 years of age), or
advanced relapsed or refractory microsatellite-instability-high (msi-h) solid tumors (6 months to <18 years of age), or
advanced relapsed or refractory tumor-mutational burden-high ≥10 mutation/mb (tmb-h) solid tumors (6 months to <18 years of age), or
with adjuvant treatment of resected high-risk stage iib, iic, iii, or iv melanoma in children 12 years to <18 years of age

part 1 will find the maximum tolerated dose (mtd)/maximum administered dose (mad), confirm the dose, and find the recommended phase 2 dose (rp2d) for pembrolizumab therapy. part 2 will further evaluate the safety and efficacy at the pediatric rp2d.

the primary hypothesis of this study is that intravenous (iv) administration of pembrolizumab to children with either advanced melanoma; a pd-l1 positive advanced, relapsed or refractory solid tumor or other lymphoma; advanced, relapsed or refractory msi-h solid tumor; or rrchl, will result in an objective response rate (orr) greater than 10% for at least one of these types of cancer. the 10% assessment does not apply to the msi-h and tmb-h cohorts.

with amendment 8, enrollment of participants with solid tumors and of participants aged 6 months to <12 years with melanoma were closed. enrollment of participants aged ≥12 years to ≤18 years with melanoma continues. enrollment of participants with msi-h and tmb-h solid tumors also continues.","inclusion criteria:

between 6 months and <18 years of age on day of signing informed consent is documented.
histologically- or cytologically-documented, locally-advanced, or metastatic solid malignancy or lymphoma that is incurable and has failed prior standard therapy, or for which no standard therapy exists, or for which no standard therapy is considered appropriate
any number of prior treatment regimens
tissue (or lymph node biopsy for rrchl participants) available from an archival tissue sample or, if appropriate, a newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
advanced melanoma or pd-l1-positive advanced, relapsed, or refractory solid tumor or lymphoma
measurable disease based on recist 1.1 (or based on iwg [cheson, 2007] [i.e., measurement must be >15 mm in longest diameter or >10 mm in short axis] for rrchl participants)
participants with neuroblastoma with only metaiodobenzylguanidine (mibg)-positive evaluable disease may be enrolled
lansky play scale ≥50 for participants from 6 months up to and including 16 years of age; or karnofsky score ≥50 for participants >16 years of age
adequate organ function
female participants of childbearing potential should have a negative urine or serum pregnancy test within 72 hours before the first dose of study medication
female participant is not a woman of childbearing potential (wocbp) or is a wocbp who is abstinent from heterosexual intercourse or using contraception during the intervention period and for at least 120 days after the last dose of study intervention
contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
demonstrate adequate organ function.

exclusion criteria:

currently participating and receiving study therapy in, or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the date of allocation/randomization
diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the date of allocation/randomization
prior systemic anti-cancer therapy including investigational agent within 2 weeks prior to study day 1 or not recovered from adverse events due to a previously administered agent
prior radiotherapy within 2 weeks of start of study treatment
known additional malignancy that is progressing or requires active treatment with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (eg, breast carcinoma, cervical carcinoma in situ) with potentially curative therapy, or in situ cervical cancer
known active central nervous system (cns) metastases and/or carcinomatous meningitis
tumor(s) involving the brain stem
severe hypersensitivity (≥ grade 3) to pembrolizumab and/or any of its excipients
active autoimmune disease that has required systemic treatment in past 2 years; replacement therapy (such as thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is acceptable
has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
active infection requiring systemic therapy
pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial through 120 days after the last dose of study medication
prior therapy with an anti-programmed cell death (pd)-1, anti-pd-ligand 1 (anti-pd-l1), anti-pd-l2 agent, or any agent directed to another stimulatory or inhibitory t-cell receptor (eg, cytotoxic lymphocyte associated protein-4 [ctla-4], ox-40, cd137)
human immunodeficiency virus (hiv)
hepatitis b or c
known history of active tuberculosis (tb; bacillus tuberculosis)
received a live vaccine within 30 days of planned start of study medication
has undergone solid organ transplant at any time, or prior allogeneic hematopoietic stem cell transplantation within the last 5 years. (participants who have had an allogeneic hematopoietic transplant >5 years ago are eligible as long as there are no symptoms of graft versus host disease [gvhd].)
history or current evidence of any condition, therapy, or laboratory abnormality, or known severe hypersensitivity to any component or analog of the trial treatment, that might confound the results of the trial, or interfere with the participant's participation for the full duration of the study
known psychiatric or substance abuse disorders that would interfere with the requirements of the study",1,1,1,0,0,0,0.5,17.0,Pleura,Pleura,0,0,All
30,30,30,264,NCT02355379,2023-08-16,randomised study evaluating adjuvant chemotherapy after resection of stage iii colonic adenocarcinoma in patients of 70 and over,"randomised phase iii study evaluating adjuvant chemotherapy after resection of stage iii colonic adenocarcinoma in patients of 70 and over intergroup trial: ffcd, gercor, gerico, unicancer-gi",ADAGE,interventional,"colorectal cancer occurs mainly in elderly patients. recent estimation showed that in france more than 50% of the patients diagnosed with a colorectal cancer are 70 years old or more. adjuvant chemotherapy has demonstrated a benefit on disease-free survival and overall survival after a stage iii colon cancer resection. nevertheless adjuvant chemotherapy is poorly used in elderly patients. prognostic improvement with chemotherapy based on 5fu is suggested by a post-hoc analysis of randomized prospective clinical trial. but elderly patients in this study were highly selected and patients older than 80 represented only 0.7% of the total population. thus, there is still a concern about the benefit of adjuvant 5fu-based chemotherapy in very elderly unselected patients.

the recommended treatment for stage iii adjuvant chemotherapy is a combination of fuoropyrimidine and oxaliplatin. nevertheless oxaliplatin did not demonstrated survival advantage in elderly patients.

altogether there are still two matters of debate:

first, is there a benefit of fluoropyrimidine-based adjuvant chemotherapy for unfit elderly patients?
second, is there a benefit of oxaliplatin-based adjuvant chemotherapy for fit elderly patients? the aim of this randomized phase iii study is to evaluate the benefit for disease-free survival of adjuvant chemotherapy in elderly patient and which chemotherapy.

the elderly patient population will be dichotomized into two groups according to physician's choice after a multidisciplinary evaluation involving a geriatrician, with two different randomization assignments. the patients with an expected life-expectancy below 4 years according lee score are excluded of this study.

some biological tumour abnormalities are more frequently observed in elderly (i.e. mismatch repair deficiency), therefore an evaluation of specific biological prognostic factors is needed in elderly population.","inclusion criteria:

age ≥ 70 years
patient considered able to receive chemotherapy
lee score detailed faxed to crga
stage iii colon adenocarcinoma
r0 resection of the primary tumor
start of the potential adjuvant chemotherapy within 12 weeks after surgery
no prior chemotherapy for colon cancer
geriatric self-administered questionnaire completed faxed to crga
geriatric questionnaire completed by the team faxed to crga
effective contraception for men patients throughout treatment and for at least 6 months after discontinuation of oxaliplatin
consent signed

exclusion criteria:

other progressive disease (cancer uncontrolled for less than 2 years)
rectal cancer (located less than 15 cm from the anal verge endoscopy or sub-peritoneal)
anc <2000 / mm3 for group 1 and anc <1500 / mm3 for group 2 and platelets <100,000 / mm3 or hemoglobin <9 g / dl
neuropathy for patients in group 1
known deficit of dihydropyrimidine dehydrogenase (dpd)
patients with severe hepatic insufficiency
any contrindication to the drugs used in the study
inability to submit to medical follow-up for geographical, social or psychological reasons.",1,0,0,1,0,0,75.0,200.0,Colon,Colon,1,0,All
31,31,31,272,NCT02386709,2021-05-21,study evaluating the utility of 18f-fdg pet in assessing early response to neoadjuvant chemotherapy in patients with mammary gland cancer,study evaluating the utility of 18f-fdg pet in assessing early response to neoadjuvant treatment in patients with mammary gland cancer,TREN,interventional,"neoadjuvant chemotherapy is frequently proposed to patients with mammary gland cancer. the aim is to reduce tumor volume before surgical therapy. obtaining a pathologic complete response (pcr) is regarded as a good prognostic factor with less risk of recurrence. the rate of pcr is about 20%, although there are important variations according to tumor subtype and the type of treatment. the objective of the new therapeutic strategies is to increase this response rate.

the purpose of this study is to investigate the possibility of early evaluation of neoadjuvant chemotherapy response after one cycle of neoadjuvant chemotherapy by positron emission tomography (pet) with (18) f-fluorodeoxyglucose (fdg) in patients.","inclusion criteria:

patient having been informed of the study
patient affiliated to a social health insurance
≥ 18 years
patient presenting a breast cancer histologically confirmed
indication of neoadjuvant chemotherapy treatment (classification uicc: ii or iii)
patient agrees with exploitation of his clinical, biological and image data

exclusion criteria:

distant metastasis
contraindications to chemotherapy
contraindications to surgery
refusal
serious illness not balanced, subjacent infection
pregnancy or breast feeding
diabetes not controlled (glycemia> 8 mmol/l)
psychiatric disease
patient under supervision, trusteeship or safeguard of justice",1,0,0,0,0,1,18.0,200.0,Breast,Breast,0,1,All
32,32,32,273,NCT02386800,2023-10-17,cinc424a2x01b rollover protocol,"open label, multi-center, phase iv study of ruxolitinib or ruxolitinib and panobinostat combination, for patients who have completed prior global novartis or incyte sponsored studies",,interventional,"this is a long term safety study for patients that have been treated with either ruxolitinib or a combination of ruxolitinib with panobinostat, on a novartis or incyte sponsored study, who have been judged by the study investigator to benefit from ongoing treatment.","key inclusion criteria:

patient is currently enrolled in a novartis gdd or gma-sponsored or incyte-sponsored clinical study, are receiving either ruxolitinib or combination of ruxolitinib and panobinostat, and fulfilled all of the requirements of the parent protocol.
patient is currently benefiting from the treatment with ruxolitinib monotherapy or combination of ruxolitinib and panobinostat, as determined by the investigator
patient has demonstrated compliance, as assessed by the investigator, with the parent study protocol requirements
patient currently has no evidence of progressive disease, as determined by the investigator, following previous treatment with ruxolitinib or combination of ruxolitinib and panobinostat

key exclusion criteria:

patient has been permanently discontinued from study treatment in the parent study due to any reason.
patient's indication is currently approved and reimbursed in the corresponding country for ruxolitinib monotherapy or combination of ruxolitinib and panobinostat.
pregnant or nursing (lactating) women.
female patients of childbearing potential (e.g. are menstruating) who do not agree to abstinence or, if sexually active, do not agree to the use of highly effective contraception, throughout the study and for up to 30 days after stopping study treatment.

other protocol-defined inclusion / exclusion criteria may apply.",1,0,0,0,1,0,0.0833333333333333,200.0,Colon,Pleura,0,1,All
33,33,33,275,NCT02389244,2023-11-06,a phase ii study evaluating efficacy and safety of regorafenib in patients with metastatic bone sarcomas,"a randomized phase ii, placebo-controlled, multicenter study evaluating efficacy and safety of regorafenib in patients with metastatic bone sarcomas",REGOBONE,interventional,"indication:

metastatic bone sarcomas: conventional high grade osteosarcoma, ewing sarcoma of bone, intermediate or high-grade chondrosarcomas and chordomas and either bone or soft tissue metastatic cic-rearranged sarcomas","inclusion criteria:

patients must have histologically confirmed diagnosis of bone sarcoma (osteosarcoma, ewing sarcoma of bone, chondrosarcoma or chordoma);
patients with confirmed disease progression at study entry;
metastatic disease not amenable to surgical resection or radiation with curative intent;
patients must have measurable disease;

prior treatment :

at least one, but no more than two prior chemotherapy regimen for metastatic disease for osteosarcoma, chondrosarcoma and ewing sarcoma; neo-adjuvant /maintenance therapy are not counted towards this requirement. chordoma not pretreated or with 1 or 2 prior (combination) chemotherapy regimen or with one or two prior molecularly targeted therapy, but no more than 2 prior lines of treatment (whatever the indication) can be included. at least 4 weeks since last chemotherapy (6 weeks in case of nitrosoureas and mitomycin c), immunotherapy or any other pharmacological treatment and/or radiotherapy;

age ≥10 years for osteosarcomas, ewing sarcomas and chondrosarcomas (for chordomas, patients must be ≥18 years);
body surface area ≥1.30 m²;
life expectancy of greater than 3 months;
eastern cooperative oncology group (ecog) performance status <2 (karnofsky ≥60%) for adults patients;
karnofsky scale ≥ 60% for children aged >12 years old / lansky scale ≥60% for children aged ≤12 years old;

patients must have adequate bone marrow, renal, and hepatic function, as evidenced by the following within 7 days of study treatment initiation: normal organ function as defined below:

absolute neutrophil count ≥1.5 giga/l
platelets ≥100 giga/l
hemoglobin ≥9 g/dl
serum creatinin ≤1.5 x upper limit of normal (uln)
glomerular filtration rate (gfr) ≥30 ml/min/1.73 m² according to the modified diet in renal disease (mdrd) abbreviated formula
aspartate transaminase (ast) and alanine transaminase (alt) ≤2.5 x uln
bilirubin ≤1.5 x uln
alkaline phosphatase ≤2.5 x uln (≤5 x uln in patient with liver involvement of their cancer). if alkaline phosphatase >2.5 uln, hepatic isoenzymes 5-nucleotidase or gamma-glutamyl transferase (ggt) tests must be performed; hepatic isoenzymes 5-nucleotidase must be within the normal range and/or ggt <1.5 x uln;
lipase ≤1.5 x uln;
spot urine must not show 1+ or more protein in urine or the patient will require a repeat urine analysis. if repeat urinalysis shows 1+ protein or more, a 24-hour urine collection will be required and must show total protein excretion <1000 mg/24 hours
international normalized ratio(inr)/ partial thromboplastin time (ptt) ≤1.5 x uln;
recovery to national cancer institute-common terminology criteria for adverse events (nci-ctcae) v4.0 grade 0 or 1 level or recovery to baseline preceding the prior treatment from any previous drug/procedure related toxicity (except alopecia, anemia, and hypothyroidism);
women of childbearing potential and male patients must agree to use adequate contraception for the duration of study participation and up to 3 months following completion of therapy;
women of childbearing potential must have a negative serum β-hcg pregnancy test within 7 days prior randomization and/or urine pregnancy test within 48 hours before the first administration of the study treatment;
signed informed consent form by adult patients and/or patients parents/legal representatives (if age <18 years) and age appropriate assent form by the patients' parents/legal representatives obtained before any study specific procedure is conducted;
patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures;
patients or parents/legal representatives affiliated to the social security system.

exclusion criteria:

prior treatment with any vegfr inhibitor;
soft tissue sarcoma;
other cancer (different histology) within 5 years prior to randomization;
major surgical procedure, open biopsy, significant trauma, within the last 28 days before randomization;

cardiovascular dysfunction:

left ventricular ejection fraction (lvef) <50%
congestive heart failure (new york heart association [nyha]) ≥2
myocardial infarction <6 months before study
cardiac arrhythmias requiring therapy
uncontrolled hypertension
unstable angina or new-onset angina
arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within the last 6 months before randomization;
severe hepatic impairment (child-pugh c);
ongoing infection > grade 2 according to nci-ctcae v4.0;
known history of human immunodeficiency virus (hiv) infection;
active hepatitis b or c or chronic hepatitis b or c requiring treatment with antiviral therapy;
difficulties with swallowing study tablets;
prior anticancer therapy, including radiotherapy, endocrine therapy, immunotherapy, chemotherapy (ct) within the last 4 weeks (6 weeks for nitrosoureas and mitomycin c), or other investigational agents ; concomitant antalgic palliative radiotherapy allowed;
concurrent enrolment in another clinical trial in which investigational therapies are administered;
known hypersensitivity to the active substance or to any of the excipients;
pregnant women, women who are likely to become pregnant or are breast-feeding;
for adult patients, individual deprived of liberty or placed under the authority of a tutor;
patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial;
patients with history of non compliance to medical regimens or unwilling or unable to comply with the protocol;
interstitial lung disease with ongoing signs and symptoms at the time of informed consent;
non-healing wound, non-healing ulcer, or non-healing bone fracture;
patients with evidence or history of any bleeding diathesis, irrespective of severity;
any hemorrhage or bleeding event ≥ ctcae grade 3 within 4 weeks prior to the start of study medication;
use of biological response modifiers, such as granulocyte colony stimulating factor (g-csf), within 3 weeks of study entry.",1,0,1,0,0,0,10.0,200.0,Pleura,Pleura,0,0,All
34,34,34,284,NCT02416388,2020-10-16,"study to improve os in 18 to 60 year-old patients, comparing daunorubicin versus high dose idarubicin induction regimens, high dose versus intermediate dose cytarabine consolidation regimens, and standard versus mmf prophylaxis of gvhd in allografted patients in first cr","phase ii/iii randomized study to improve overall survival in 18 to 60 year-old patients, comparing daunorubicin versus high dose idarubicin induction regimens, high dose versus intermediate dose cytarabine consolidation regimens, and standard versus mycophenolate mofetil prophylaxis of graft versus host disease in allografted patients in first cr : a backbone intergroup-1 trial",BIG-1,interventional,"this open label, multicenter phase ii/iii study with multiple randomization phases at differents stages of aml treatment (induction, consolidation and hsct where applicable) is designed to improve os in younger (18 to 60 year-old) patients, with aml risk-adapted patient strategies. within the intermediate risk aml group, optimal gvhd prophylaxis following allogeneic sct in first cr, after either myeloablative (mac) or reduced intensity (ric) conditioning, will also be evaluated. with an adaptative design, this clinical trial could test up to 3 novel aml agents of interest.","inclusion criteria (at diagnosis) :

age ≥ 18 years and < 61 years
with a newly diagnosed de novo or secondary type aml (post myelodysplastic syndrome mds or therapy-related aml)
no prior treatment for neither aml (with the exception of hydroxyurea), nor mds (with the exception of epo)
ecog performance status ≤ 3
absence of severe uncontrolled infection
no cardiac contraindications for the use of anthracyclines : decompensated or uncontrolled heart failure, recent myocardial infarction, current signs of cardiac impairment, uncontrolled arrhythmias, lvef (left ventricular ejection fraction) < 50%
total bilirubin ≤ 2 x upper limit of normal (unl), asat(sgot) and alat (sgpt) ≤ 2.5 x unl, creatinine < 150 µmol/l, unless aml-related out of range values
genetic mutation testing of the flt3 (flt3-itd ou flt3-tkd) gene, performed in local or central laboratory

use of appropriate methods of contraception:

for patients treated with midostaurin:

women of childbearing potential should use appropriate methods of contaception throughout treatment, and for 5 months post cessation of treatment
men will need to use condoms during intercourse throughout treatment, and for 5 months post cessation of treatment with midostaurin
patients who are covered by or beneficiaries of a social security system (social security or universal medical coverage)
patients who have read and understood the information sheet and signed the informed consent form

exclusion criteria (at diagnosis) :

1.patients with acute promyelocytic leukemia (apl), as confirmed either by t(15;17) or by the presence of pml-rara fusion transcripts 2.patients with core binding factor (cbf) aml, as confirmed either by t(8;21), t(16,16) or inv(16), or by fusion transcripts resulting from these cytogenetic abnormalities (runx1-runx1t1, cbfb-myh11).

3.patients with secondary aml arising from myeloproliferative disorders previously known according to the 2008 who classification 4.patients with ph1+ aml or previous ph1+ disorder (chronic myelogenous leukemia) 5.severe psychiatric or organic disorder, supposed to be independent from aml, that would contraindicate treatment, including allogeneic hsct 6.no psychological, familial, social, or geographic reason that would compromise clinical follow up 7.history of uncontrolled cancer for the last 2 years, with the exception of basal cell carcinoma or carcinoma in situ of the cervix 8.uncontrolled severe infection 9.patients with positive serology for hiv-1 and -2, or htlv -1 and -2, or active hepatitis virus b or c infection 10.pregnant or lactating women 11.legal incapacity (patients under tutorship, curatorship or judicial protection)

------------------------------------------

for randomization r4-vos (post-induction/salvage) :

inclusion criteria

patients enrolled in the big-1 trial at diagnosis
patient presenting with aml in first cr or crp/cri after induction or one cycle of salvage therapy (confirmed in the 15 days preceding r4-vos)
favorable or intermediate risk aml patients, as stratified with big-1 prognostic classification
patients randomized to r2-idac arm (intermediate dose cytarabine)
ecog performance status ≤ 2
left ventricular ejection fraction (lvef) at least 40% by multiple gated acquisition (muga) scan or echocardiogram (echo)

local clinical laboratory values as follows:

o serum creatinine ≤ 2.0 mg/dl

o total bilirubin ≤ 1.5 x the upper limit of normal (uln)

aspartate aminotransferase (ast) ≤ 2.5 x uln
alanine aminotransferase (alt) ≤ 2.5 x uln
signed written informed consent for vosaroxin study (r4-vos)
women of childbearing potential must have a negative pregnancy test within 8 days before randomization r4-vos and commit to the use of effective contraception during the period of treatment and up to 36 days after vosaroxin has been stopped. men must use effective contraception during the treatment period and up to 96 days after vosaroxin has been stopped.

exclusion criteria

1.patients classified in the unfavorable risk group according to the big-1 protocol classification 2.complete remission is not attained (cr, crp/cri) after induction and/or salvage therapy 3.positive pregnancy test 4.severe uncontrolled infection such as sepsis, or multiple organ dysfunction syndrome, uncontrolled fever 5.documented uncontrolled fungal infection (positive blood test and cultures) 6.history of myocardial infarction, unstable angina, cerebrovascular accident (cva) or transient ischemic attack (tia) in the 3 months before randomization 7.patient under hemodialysis (hd) or peritoneal dialysis (pd)

------------------------------------------

for randomization r4-dex (post-induction/salvage) :

inclusion criteria

patients enrolled in the big-1 trial at diagnosis
patient presenting with aml in first cr or crp/cri after induction or one cycle of salvage therapy (confirmed in the 15 days preceding r4-dex)
favorable or intermediate risk aml patients, as stratified with big-1 prognostic classification
ecog performance status ≤ 2

local clinical laboratory values as follows:

serum creatinine ≤ 150 µmol/l
total bilirubin ≤ 1.5 x the upper limit of normal (uln)
aspartate aminotransferase (ast) ≤ 2.5 x uln
alanine aminotransferase (alt) ≤ 2.5 x uln
signed written informed consent for dexamethasone study (r4-dex)

exclusion criteria

1.severe uncontrolled infection such as sepsis, or multiple organ dysfunction syndrome, uncontrolled fever 2.documented uncontrolled fungal infection (positive blood test and cultures 3.history of myocardial infarction, unstable angina, cerebrovascular accident (cva) or transient ischemic attack (tia) in the 3 months before randomization 4.patient under hemodialysis (hd) or peritoneal dialysis (pd)

--------------------------------------

for randomization r4-ven (post-induction/salvage) :

inclusion criteria

age 18 - 60 years at inclusion in big-1 protocol
diagnosis of aml according to who classification de novo or secondary to myelodysplastic syndrome (myelodysplastic syndrome must not have been treated except by esa, lenalidomide or non-chemotherapy) or therapy-related aml
patients included in the big-1 protocol
patients in first cr or crp/cri following 1 or 2 courses of induction chemotherapy according to big-1 protocol and who are planned to receive consolidation.
patients stratified within the favorable and intermediate risk groups as defined by big-1 protocol
ecog performance status ≤ 2
left ventricular ejection fraction (lvef) at least 40% by multiple gated acquisition (muga) scan or echocardiogram (echo)
creatinine clearance ≥ 30 ml/min (calculated by the usual method of each institution), total bilirubin ≤ 1.5 times the uln; asat and alat ≤ times the upper limit of normal (uln)
absence of uncontrolled infection
women of childbearing potential must agree to use effective contraception without interruption throughout the study and for a further 3 months after the end of treatment
written signed informed consent

exclusion criteria

1.aml stratified in the unfavorable big-1 risk-group. 2.diagnosis of acute promyelocytic leukemia or cbf aml (ie. aml with t(8;21), t(16,16) or inv(16), or their molecular equivalents runx1-runx1t1 and cbfb-myh11) 3.aml secondary to prior myeloproliferative disorder according to who classification (2008) and philadelphia chromosome-positive aml (ph1+) 4.absence of cr/crp/cri after a maximum of two chemotherapy cycles 5.severe medical or mental condition precluding the administration of protocol treatments 6.prior history of cancer unless controlled for at least 2 years and except for basocellular cutaneous cancers and in situ cervix cancers 7.positive pregnancy test 8.breast feeding 9.uncontrolled infection such as sepsis, or multiple organ dysfunction syndrome, uncontrolled fever 10.documented uncontrolled fungal infection (positive blood test and cultures) 11.prior venetoclax exposure 12.known hbv with detectable viral load 13.known hiv positive patients 14.known hypersensitivity to any of the study medication 15.history of myocardial infarction, unstable angina, cerebrovascular accident (cva) or transient ischemic attack (tia) in the 3 months before randomization 16.patient under hemodialysis (hd) or peritoneal dialysis (pd) 17.concomitant treatment with cytochrome cyp3a4 inhibitor which cannot be stopped during venetoclax administration only for phase 1 18.during the phase 2, for patients randomized in the idac + venetoclax arm, if concomitant treatment with cytochrome cyp3a4 inhibitor cannot be stopped, a dose reduction of 70% of venetoclax must be apply

--------------------------------------

for randomization r3 (before allohsct):

inclusion criteria

patients enrolled in the big-1 trial at diagnosis

patient presenting with aml in first cr or crp/cri treated in the big-1 trial and classified in the intermediate risk group, namely:

either initially favorable but poor molecular responders for npm1 mrd: npm1 mutation, without flt3-itd mutation or with an flt3-itd ratio < 0.50 and mrd2 positive blood (decrease of less than 4 log from baseline at diagnosis)).
or initially favorable but requiring two cycles of chemotherapy (a salvage therapy) to obtain the first cr/crp/cri
or other immediate intermediaries
no metastatic or progressive cancer, with the exception of basal cell skin carcinoma and cervical carcinoma in situ
patients with general condition preserved (ecog ≤ 3) and with no uncontrolled severe infection
women of childbearing age must make use of effective contraception
patients who are covered by or beneficiaries of a social security system (social security or universal medical coverage).
patients who have read and understood the information sheet and signed the informed consent form

exclusion criteria

complete remission is not obtained (cr, crp/cri) after induction and/or salvage therapy
patient presenting with aml in first cr or crp/cri treated in the big-1 trial and classified either in the favorable risk group or the unfavorable risk group
patients with a severe organ or psychiatric pathology, presumed to be independent of aml and contraindicating the allograft
patients who, for family, social or geographic reasons, do not wish to be regularly monitored via consultation
uncontrolled severe infection at the time of inclusion
serology positive for hiv 1 or 2 or htlv 1 or 2, or active hbv or hcv viral infection
pregnant women (beta-hcg positive) or currently breastfeeding
adult patient who is incapacitated, under wardship, legal guardianship, or under the protection of the courts
patients under state medical assistance (ame)",1,0,1,1,0,0,18.0,61.0,Brain,Brain,0,0,All
35,35,35,312,NCT02491840,2023-08-10,biomoleculars markers of sensitivity to pre- and post-operative chemotherapy of gastric and cardia adenocarcinomas: a pilot study,biomoleculars markers of sensitivity to pre- and post-operative chemotherapy of gastric and cardia adenocarcinomas: a pilot study,,interventional,"some subtypes of gastric and cardia tumors such as adenocarcinoma or gastric linitis with disseminated cells respond poorly to the pre-operative chemotherapy, and some of them do not respond to chemotherapy usually performed. doing chemotherapy in these patients could delay their surgical management. the completion of chemotherapy for these patients would be a bad prognosis factor according to recent data from the literature. therefore, the aim of this research is to find prognostic markers of sensitivity to chemotherapy usually performed. the investigators are going to use biopsies realized at diagnosis and select patients ""good and bad"" responders.

primary purpose:

to study cardia and gastric tumors, molecular markers sensitivity to pre- and post- perative chemotherapy protocols (eox protocol ... folfox) or chemoradiation

secondary purposes:

to assess the impact of patients' lifestyle (via a questionnaire) on the response to chemotherapy
to study markers of cancer stem cells
to correlate clinical and molecular markers with patient survival and quality of life questionnaires
to characterize the expression levels (met, her2, fgfr2) and mutations (p53 ras) in frequently deregulated genes in gastric cancers.
to characterize the level of expression of predictive candidate markers (δnp73, tap73, hdac4, mir140, ezh2, cxcl12, cxcr4, cxcr7) found in the literature.
to correlate the abnormalities found in the with tumor stages (before and after chemotherapy) and with 5 years overall survival and progression-free patients","inclusion criteria:

gastric adenocarcinoma (any location) or cardia adenocarcinoma

age> 18 years
who index≤ 3
subject having signed an informed consent

exclusion criteria:

other cancers undergoing chemotherapy treatment
pregnant or breastfeeding
inability to understand information (understanding with difficulties ...)",1,0,0,0,0,1,18.0,200.0,Gastric,Gastric,0,1,All
36,36,36,331,NCT02534649,2023-02-28,bergonie institut profiling : fighting cancer by matching molecular alterations and drugs in early phase trials,bergonie institut profiling : fighting cancer by matching molecular alterations and drugs in early phase trials,BIP,interventional,"this is a biology driven, monocentric study designed to identify actionable molecular alterations in cancer patients with advanced disease.

in this trial, high throughput analysis will be carried out using next generation sequencing, and immunological profiling.

patients included in the bip study and for whom a targetable genomic alteration had been identified might be subsequently included in an early phase trials running at institut bergonie or another french hospital.","inclusion criteria:

age ≥ 18 years,
histology: solid malignant tumor or hematological malignancy,
deleted msa9
deleted msa9,
deleted msa9,
deleted msa9,
patient with a social security in compliance with the french law relating to biomedical research (article l.1121-11 of french public health code),
voluntary signed and dated written informed consent prior to any study specific procedure.

exclusion criteria:

deleted msa9
deleted msa9
deleted msa9
deleted msa9
deleted msa9
deleted msa9
deleted msa9
deleted msa9
individuals deprived of liberty or placed under guardianship
pregnant or breast feeding women,
previous enrolment in the present study.",1,0,0,0,0,1,18.0,200.0,Brain,Brain,0,1,All
37,37,37,345,NCT02576431,2023-11-03,a study to test the effect of the drug larotrectinib in adults and children with ntrk-fusion positive solid tumors,a study to learn how well the drug larotrectinib works in adults with different solid cancers with a change in the genes called ntrk fusion,NAVIGATE,interventional,"this research study is done to test how well different types of cancer respond to the drug called larotrectinib. the cancer must have a change in a particular gene (ntrk1, ntrk2 or ntrk3). larotrectinib is a drug that blocks the actions of these ntrk genes in cancer cells and can therefore be used to treat cancer.","inclusion criteria:

locally-advanced or metastatic malignancy with an ntrk1, ntrk2, or ntrk3 gene fusion, identified through molecular assays as routinely performed at clia or other similarly-certified laboratories. subjects who have an ntrk gene fusion identified in a lab where clia or equivalent certification cannot be confirmed by the sponsor at the time of consent may have been enrolled in cohort 9 as per protocol versions 1.0 - 8.0. from protocol version 9.0: clia or similar certification of the lab performing the fusion assay is required. however, patients may be included after discussion with the sponsor if the lab performing the fusion assay is not clia or similar certified.
subjects who have received prior standard therapy appropriate for their tumor type and stage of disease, or who have no satisfactory alternative treatments and in the opinion of the investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy.

subjects must have at least one measurable lesion as defined by recist v1.1 (eisenhauer et al. 2009). subjects with solid tumors without recist v1.1 measurable disease (e.g., evaluable disease only) had been eligible for enrollment to cohort 8 as per protocol versions 1.0 - 8.0, regardless of tumor type. subjects with primary cns tumors should meet the following criteria:

have received prior treatment including radiation and/or chemotherapy, with radiation completed > 12 weeks prior to c1d1 of therapy, as recommended or appropriate for that cns tumor type.
have ≥ 1 site of bi-dimensionally measurable disease (confirmed by magnetic resonance imaging [mri] and evaluable by rano criteria), with the size of at least one of the measurable lesions ≥ 1 cm in each dimension and noted on more than one imaging slice.
imaging study performed within 28 days before enrollment. if on steroid therapy, the dose must be stable for at least 7 days immediately before and during the imaging study.

must be neurologically stable based on stable neurologic exam for 7 days prior to enrollment.

for subjects eligible for enrollment to bone health cohort, inclusion criterion 3 is modified as the following:

subjects must have at least one lesion at baseline (measurable or non-measurable as defined by recist v1.1 or rano criteria, as appropriate to tumor type).
subjects with primary cns tumors must be neurologically stable based on stable neurologic exam for 7 days prior to enrollment.
at least 18 years of age
performance status: eastern cooperative oncology group (ecog) score ≤ 3. if enrolled with primary cns tumor to be assessed by rano, karnofsky performance score (kps) ≥ 50%.
tumor tissue before treatment (mandatory). if neither fresh tissue can be obtained nor archival tissue is available patients might be enrolled after consultation with the sponsor.

adequate organ function as defined by the following criteria:

serum ast and serum alt < 2.5 x upper limit of normal (uln), or ast and alt < 5 x uln if liver function abnormalities are due to underlying malignancy
total bilirubin < 2.5 x uln, except in the setting of biliary obstruction. subjects with a known history of gilberts disease and an isolated elevation of indirect bilirubin are eligible
serum creatinine < 2.0 x uln or an estimated glomerular filtration rate ≥ 30 ml/minute using the cockcroft-gault formula: (140- age) x body weight (kg) x 0.85 (if female)/serum creatinine (mg/dl) x 72 with either result acceptable for enrollment.
ability to comply (or for guardian to ensure compliance) with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation.
willingness of men and women of reproductive potential to use double effective birth control methods, defined as one used by the subject and another by his/her partner, for the duration of treatment and for 1 month following study completion.
for subjects eligible for enrollment to bone health cohort only: life expectancy of at least 6 months, based on investigator assessment.

exclusion criteria:

investigational agent or anticancer therapy within 2 weeks prior to the planned start of larotrectinib or 5 half-lives, whichever is shorter, and without recovery of acute and/or clinically significant toxicities from that therapy.
prior progression while receiving approved or investigational tyrosine kinase inhibitors targeting trk. subjects who received less than 28 days of treatment and discontinued because of intolerance or toxicity are eligible.
symptomatic or unstable brain metastases. (note: subjects with asymptomatic brain metastases are eligible to participate in the study.) subjects with primary cns tumors are eligible.
uncontrolled concurrent malignancy that would limit assessment of efficacy of larotrectinib. allowed conditions may include, but are not limited to in situ cancers of cervix, breast, or skin, superficial bladder cancer, limited-stage prostate cancer, and basal or squamous cancers of the skin.

active uncontrolled systemic bacterial, viral, or fungal infection ctcae grade ≥ 2; unstable cardiovascular disease, or other systemic disease that would limit compliance with study procedures. unstable cardiovascular disease is defined as:

in adults, persistently uncontrolled hypertension defined as systolic blood pressure (bp) > 150 mmhg and/or diastolic bp > 100 mmhg despite antihypertensive therapy.
myocardial infarction within 3 months of screening.
stroke within 3 months of screening.
inability to discontinue treatment with a strong cyp3a4 inhibitor or inducer
currently recovering from aes/ adrs due to previous treatments (excluding alopecia). inclusion is only advised once the ae/adr resolves or recovers to baseline or at least to ctcae grade 1.
known or suspected hypersensitivity against the active substance or any of the ingredients of the imp.
known history of hiv infection. all patients must be screened for hiv up to 28 days prior to study drug start using a blood test for hiv according to local regulations.
hbv or hcv infection. all patients must be screened for hbv and hcv up to 28 days prior to study drug start using the routine hepatitis virus laboratorial panel. patients positive for hbsag or hbcab will be eligible if they are negative for hbvdna. patients positive for anti-hcv antibody will be eligible if they are negative for hcv-rna.",1,0,1,0,0,0,18.0,200.0,Brain,Brain,0,0,All
38,38,38,353,NCT02584933,2023-10-16,roll-over study to allow access to certinib (ldk378) for patients who are on ceritinib treatment in a novartis-sponsored study,"an open-label, multi-center, phase iv roll-over study in patients with alk positive malignancies who have completed a novartis-sponsored ceritinib (ldk378) study and are judged by the investigator to benefit from continued treatment with ceritinib",,interventional,"the rollover study will provide ceritinib to patients who are currently receiving treatment with ceritinib within a novartis-sponsored study and in the opinion of the investigator, would benefit from continued treatment with ceritinib.","inclusion criteria:

patient is currently receiving treatment with ceritinib within a novartis-sponsored study which has fulfilled the requirements for the primary objective and, in the opinion of the investigator, would benefit from continued treatment.
patient has demonstrated compliance, as assessed by the investigator, with the parent study protocol requirements.
willingness and ability to comply with scheduled visits, treatment plans and any other study procedures.
written informed consent obtained prior to enrolling in the roll-over study and receiving study medication. if consent cannot be expressed in writing, it must be formally documented and witnessed via an independent trusted witness.

exclusion criteria:

patient has been permanently and prematurely discontinued from ceritinib study treatment in the parent study due to any reason.
patient currently has unresolved toxicities for which ceritinib dosing has been interrupted in the parent study.
pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive serum hcg laboratory test.
women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 3 months afer stopping ceritinib treatment.
sexually active males unless they use a condom during intercourse while taking drug and for 3 months after stopping ceritinib and should not father a child for at least 3 months after the last dose of treatment.",1,0,0,0,1,0,12.0,200.0,Lung,Brain,1,0,All
39,39,39,354,NCT02584985,2019-01-22,"evaluate efficacy, morbidity and functional outcome of endoscopic trananal proctectomy vs standard transabdominal laparoscopic proctectomy for rectal cancer","a multicentric randomised trial to evaluate efficacy, morbidity and functional outcome of endoscopic trananal proctectomy versus standard transabdominal laparoscopic proctectomy for low lying rectal cancer (etap-greccar 11)",ETAP,interventional,"standard surgical treatment of mid and low rectal cancer is total mesorectal excision (tme). originally performed by open surgery, tme demonstrated improved local control and reduced urogenital morbidity. laparoscopic approach has been validated by several randomised controlled trials: laparoscopic approach offers to the patient a better post-operative recovery, a lower risk of wound hernia and comparable oncological results. however, the risk of conversion to open procedure remains significant.

endoscopic transanal proctectomy allows retrograd mesorectal excision, performing the whole pelvic dissection via a specific-moderate cost device. the procedure is then completed by a briefer transabdominal laparoscopic step to mobilise the colon and perform inferior mesenteric vessels ligation, prior to low coloanal anastomosis. the originality of this approach is to perform a surgical dissection via an extra peritoneal route, without peritoneal and abdominal wound trauma. this focuses on new technical improvement in the area of mini-invasive pelviabdominal surgery using natural orifice as surgical access. this approach offer closer and better exposure of pelvic dissection plane and could improve oncological quality and pelvic nerve preservation. it could be profitable to postoperative patient outcome. however rates and type of cancer-recurrences as well as functional results have to be assessed in a controlled study. this technique has shown to be feasible and reproducible through early clinical series. conversion rates appear to be lower than published rates of laparoscopic approach, markedly inferior to 10%. compiled rates of morbidity (27.8%), r1 resection* (6%), mesorectum macroscopic integrity (100%) appear to be comparable to laparoscopic approach results. however functional results as well as urologic morbidity have to be evaluated in comparative studies. in a preliminary retrospective comparative (n=72) we founded comparable oncological quality criteria (r1 resection 5.9% vs 10.5% p 0.74, grade 3 mesorectal integrity 57.5 vs 56.2 p 0.99), lower conversion rate to open procedure (2.9% vs 23.6% p 0.011), shorter in-hospital stay (8 vs 9 days p 0.038). comparable morbidity rates (dindo 1-4 27% vs 34% p 0.52) and functional results (kirwan 1/2 80.3% vs 80.6% p 0.94) were also founded. these data need to be confirmed. to this date, endoscopic transanal proctectomy has been evaluated through preliminary studies including several short series demonstrating the feasibility of the technique and showing low morbidity. for some authors the benefit of transanal approach is significant in difficult cases such as male patient and narrow pelvis. very recently, two non randomised comparative studies were published with conclusions close to those in our study.

investigators propose, with the support of the greccar group, to conduct a national, multicenter, open-label randomized study based on oncological non-inferiority (r1 resection rate) for the main objective, comparing endoscopic transanal proctectomy to standard transabdominal laparoscopic proctectomy, for low lying rectal cancer requiring manual colo-anal anastomosis. there is a clear expected benefit expected for the patients through the etap procedure in term of post operative short term outcome, risk of conversion to open procedure, risk of wound hernia.this trial could also show significant advantages in terms of quality of dissection, quality of the specimen, quality of nerve preservation.","inclusion criteria:

non metastatic stadified t3 rectal adenocarcinoma allowing sphincter-sparing procedure
tumor location or local condition justifying manual coloanal anastomosis
age >18 years
patient eligible for surgery
written informed consent
affiliation to social security system

exclusion criteria:

tumor stadified t4 with en-bloc resection
possible mechanical trans-sutural anastomosis
distant metastasis at diagnosis
any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol or follow-up schedule
patients deprived of liberty or placed under the authority of a tutor",1,0,0,1,0,0,18.0,200.0,Prostate,Prostate,0,0,All
40,40,40,365,NCT02611492,2019-10-18,a phase iii randomized trial of the reduction of chemotherapy in philadelphia chromosome-positive all of young adults,"a phase iii study, randomized, to evaluate the reduction of chemotherapy intensity in association with nilotinib (tasigna®) in philadelphia chromosome-positive (ph+) all of young adults (18-59 years old) (graaph-2014)",GRAAPH2014,interventional,the primary objective is to assess the non-inferiority of the experimental arm (arm b) compared to the control arm (arm a) in terms of major molecular response (mmolr) after the 4th cycle (mrd4) in patients aged 18-59 years old with de novo philadelphia positive (ph+) acute lymphoblastic leukemia (all),"inclusion criteria:

patient

whose blood and bone marrow explorations have been completed before the steroids prephase
aged 18-59 years old with newly-diagnosed non previously treated ph+ all according to who 2008 criteria (confirmed diagnosis of the philadelphia chromosome defined by the reciprocal translocation of chromosomes 9 and 22, t(9;22) and/or presence of the bcr-abl molecular maker)
with ≥ 20% bone marrow blasts
with eastern cooperative oncology group (ecog) performans status ≤ 3
with or without central nervous system (cns) or testis involvement
without evolving cancer (except basal cell carcinoma of the skin or ""in situ"" carcinoma of the cervix) or its chemo- or radio-therapy should be finished at least since 6 months.
having received no previous treatment for this hematological disease (including it injection)
having signed written informed consent
with efficient contraception for women of childbearing age (excluding estrogens and iud)
with health insurance coverage
who have received (or being receiving) the recommended steroid prephase.

note 1: secondary all (antecedent of chemo- or radio-therapy) can be included note 2: in case of high vascular risk (see section ""study management"") the patient will not be able to receive nilotinib unless an ultra sound doppler of the neck and lower limbs has been performed during the pre-phase and treatment validated by the medical coordinators of the protocol via the secretariat.

exclusion criteria:

patient:

previously treated with tyrosine kinase inhibitor (tki)
with another active malignancy

with general or visceral contra-indication to intensive therapy (except if considered related to the all):

aspartate aminotransferase (ast) and/or alanine aminotransferase (alt) > 2.5 x upper limit of normal range (uln)
total bilirubin > 1.5 x uln
creatinine > 1.5 x uln or creatinine clearance <50 ml/mn
serum amylase or lipase > 1.5 x uln or antecedents of acute pancreatitis

with heart failure, including at least one of the following criteria:

left ventricular ejection fraction (lvef) <50% or below the lowest normal threshold, as determined by ecg or heart failure (nyha grade iii or iv)
impossibility to measure the qt interval on ecg
complete left bundle branch block
pacemaker
congenital long qt syndrome of known familial antecedents of long qt syndrome
antecedents or current ventricular or atrial tachyarrhythmia, clinically significant
baseline bradycardia (<50 bpm) clinically significant
corrected qt interval (qtc)> 450 msec established on the mean of 3 baseline ecg
antecedents of myocardial infarct in the past 6 months
instable angor within the past 12 months
any heart condition clinically significant (i.e. congestive heart failure, uncontrolled hypertension)
active uncontrolled infection, any other concurrent disease deemed to interfere with the conduct of the study as judged by the investigator
severe evolving infection, or known hiv or human t-lymphotropic virus type i (htlv1) seropositivity, or active infection by hepatitis b or c virus
pregnant (beta-hcg) or nursing woman
women of childbearing potential not willing to use an effective form of contraception during participation in the study and at least three months thereafter. patient not willing to ensure not to beget a child during participation in the study and at least three months thereafter.
having received an investigational treatment or participation in another trial within 30 days prior to entering this study.
not able to bear with the procedures or the frequency of visits planned in the trial.
unable to consent, under tutelage or curators, or judiciary safeguard",1,0,0,1,0,0,18.0,59.0,Pleura,Pleura,0,0,All
41,41,41,370,NCT02619630,2019-10-18,multicenter study of risk-adapted treatment for t-lineage all of young adults (18-59 years old),multicenter study of risk-adapted treatment for t-lineage all of young adults (18-59 years old): evaluating the efficacy of a nelarabine based consolidation and maintenance in high-risk patients,GRAALL-2014/T,interventional,the purpose of this study is to evaluate the efficacy of nelarabine-based consolidation and maintenance therapy in term of relapse-free survival (rfs) in high-risk (hr) patients.,"inclusion criteria:

whose blood and bone marrow explorations have been completed before the steroids prephase
aged 18-59 years old with a not previously treated (including it injection) t-all newly-diagnosed according to the who 2008 definition with > 20% bone marrow blasts
with eastern cooperative oncology group (ecog) performance status < 3
with or without central nervous system (cns) involvement or testis
without other evolving cancer (except basal cell carcinoma of the skin and ""in situ"" carcinoma of the cervix) or its chemo or radio-therapy treatment finished at least since 6 months
having signed a written informed consent
with efficient contraception for women of childbearing age (excluding estrogens and iud)
having received or being receiving steroid prephase
with health insurance coverage

exclusion criteria:

with lymphoblastic lymphoma and bone marrow blasts < 20%, burkitt-type all or with antecedents of chronic myeloid leukemia (cml) or other myeloproliferative neoplasm

with contra-indication to anthracyclines or any other general or visceral contra-indication to intensive therapy except if considered related to the all:

aspartate transaminase (ast) and/or alanine transaminase (alt) > 5 x upper limit of normal range (uln)
total bilirubin ≥ 2.5 x upper limit of normal range (uln)
creatinine > 1.5 x upper limit of normal range (uln) or creatinine clearance <50 ml/mn
myocardial infarction within 6 months prior to inclusion in the trial, cardiomyopathy (nyha grade iii or iv), left ejection ventricle fraction (levf) < 50% and/or rf < 30%,
active severe infection or known seropositivity for hiv or human t cell leukemia/lymphoma virus type 1 (htlv-1) or active hepatitis b or c
other active malignancy
pregnant (beta-human chorionic gonadotropin (hcg) positive) or nursing woman
women of childbearing potential not willing to use an effective form of contraception during participation in the study and at least three months thereafter. patients not willing to ensure not to beget a child during participation in the study and at least three months thereafter
treated with any other investigational agent or participation in another trial within 30 days prior to entering this study
not able to bear with the procedures or the frequency of visits planned in the trial
unable to consent, under tutelage or curators, or judiciary safeguard",1,0,1,0,0,0,18.0,59.0,Pleura,Brain,0,1,All
42,42,42,372,NCT02625480,2023-10-13,study evaluating brexucabtagene autoleucel (kte-x19) in pediatric and adolescent participants with relapsed/refractory b-precursor acute lymphoblastic leukemia or relapsed/refractory b-cell non-hodgkin lymphoma,a phase 1/2 multi-center study evaluating the safety and efficacy of kte-x19 in pediatric and adolescent subjects with relapsed/refractory b-precursor acute lymphoblastic leukemia or relapsed/refractory b-cell non-hodgkin lymphoma (zuma-4),ZUMA-4,interventional,"the primary objectives of this study are to evaluate the safety and efficacy of brexucabtagene autoleucel (kte-x19) in pediatric and adolescent participants with relapsed/refractory (r/r) b-precursor acute lymphoblastic leukemia (all) or relapsed or refractory (r/r) b-cell non-hodgkin lymphoma (nhl).

as of october 2022, no further patients with acute b-cell acute lymphoblastic leukemia (all) will be asked to join the study. the study remains open for recruitment for patients that have b-cell non hodgkin lymphoma (nhl).","key inclusion criteria for the all cohort

relapsed or refractory b-precursor all defined as one of the following:

primary refractory disease
any relapse within 18 months after first diagnosis
relapsed or refractory disease after 2 or more lines of systemic therapy
relapsed or refractory disease after allogeneic transplant provided individual is at least 100 days from stem cell transplant at the time of enrollment

disease burden defined as at least 1 of the following:

morphological disease in the bone marrow (> 5% blasts)
minimal/measurable residual disease (mrd) positive (threshold 10^-4 by flow or polymerase chain reaction (pcr))
individuals with ph+ disease are eligible if they are intolerant to tyrosine kinase inhibitor (tki) therapy, or if they have relapsed/refractory disease despite treatment with at least 2 different tkis
age ≤ 21 years and weight ≥ 6 kg at the time of assent or consent per institutional review board (irb) guidelines
lansky (age < 16 years at the time of assent/consent) or karnofsky (age ≥ 16 years at the time of assent/consent) performance status ≥ 80 at screening

adequate renal, hepatic, pulmonary and cardiac function defined as:

creatinine clearance (as estimated by cockcroft gault or schwartz) ≥ 60 ml/min
serum alanine aminotransferase (alt)/aspartate aminotransferase (ast) ≤ 5 x upper limit of normal (uln)
total bilirubin ≤ 1.5 x uln, except in individuals with gilbert's syndrome
left ventricular shortening fraction (lvsf) ≥ 30% or left ventricular ejection fraction (lvef) ≥ 50%, as determined by an echocardiogram or multi-gated acquisition scan (muga), no evidence of pericardial effusion (except trace or physiological) as determined by an echocardiogram (echo) and no clinically significant arrhythmias
no clinically significant pleural effusion, pericardial effusion or ascites
baseline oxygen saturation > 92% on room air

key exclusion criteria for the all cohort

diagnosis of burkitt's leukemia/lymphoma according to the world health organization (who) classification or chronic myelogenous leukemia lymphoid blast crisis
history of malignancy other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) unless disease free for at least 3 years
history of severe hypersensitivity reaction to aminoglycosides or any of the agents used in this study

central nervous system (cns) involvement and abnormalities:

any cns tumor mass by imaging and/or parameningeal mass (cranial and/or spinal)
presence of central nervous system (cns)-3 disease, defined as white blood cell (wbc) ≥ 5/µl in cerebrospinal fluid (csf) with presence of lymphoblasts with or without neurologic symptoms
cns-2 disease, defined as wbc < 5/µl in csf with presence of lymphoblasts and with neurologic symptoms (see note below for further clarification).
note: neurologic symptoms may include but are not limited to cranial nerve palsy (if not explained by extracranial tumor) and clinical cord compression.
(individuals with cns-1 (no detectable lymphoblasts in the csf) and those with cns-2 without clinically evident neurological changes are eligible to participate in the study)
history or presence of cns disorder, such as cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with cns involvement, posterior reversible encephalopathy syndrome (pres), or cerebral edema with confirmed structural defects not related to lymphoma by appropriate imaging. history of stroke or transient ischemic attack within 12 months before enrollment. individuals with seizure disorders requiring active anticonvulsive medication.
history of concomitant genetic syndrome such as fanconi anemia, kostmann syndrome, shwachman-diamond syndrome or any other known bone marrow failure syndrome
history of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment
history of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment.
primary immunodeficiency
history of human immunodeficiency virus (hiv) infection or acute / chronic active hepatitis b or c infection. individuals with a history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing per current infectious diseases society of america guidelines or applicable country guidelines.
presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring iv antimicrobials for management.

prior medication:

prior cd19 directed therapy (other than blinatumomab), including car+ t cell, bispecific t cell engager (bite), and antibody drug conjugate (adc), with the exception of individuals who received brexucabtagene autoleucel (kte-x19) in this study and are eligible for re-treatment
treatment with alemtuzumab within 6 months prior to leukapheresis, or treatment with clofarabine or cladribine within 3 months prior to leukapheresis
donor lymphocyte infusion (dli) within 28 days prior to enrollment
any drug used for graft-versus-host disease (gvhd) within 4 weeks prior to enrollment
acute gvhd grade ii-iv by glucksberg criteria or severity b-d by ibmtr index; acute or chronic gvhd requiring systemic treatment within 4 weeks prior to enrollment
live vaccine ≤ 6 weeks prior to enrollment
women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant. females who have undergone surgical sterilization are not considered to be of childbearing potential
individuals of both genders of child-bearing potential who are not willing to use a birth control method considered to be highly effective per protocol from the time of consent through 6 months after conditioning chemotherapy or brexucabtagene autoleucel (kte-x19) infusion, whichever is longer.

key inclusion criteria for the nhl cohort

histologically confirmed aggressive b cell nhl

relapsed or refractory histologically confirmed aggressive b-cell nhl per 1 or more of the following:

primary refractory disease
relapsed or refractory disease after 2 or more lines of systemic therapy
relapsed or refractory disease after autologous /allogeneic transplant provided individual is at least 100 days from stem cell transplant at the time of enrollment

individuals must have received adequate prior therapy including at a minimum all of the following:

anti-cd20 monoclonal antibody, unless the investigator determines that the tumor is cd20 negative
an anthracycline-containing chemotherapy regimen
age <18 years old and weight ≥ 6kg
lansky (age < 16 years at the time of assent/consent) or karnofsky (age ≥ 16 years at the time of assent/consent) performance status ≥ 80 at screening

adequate renal, hepatic, pulmonary, and cardiac function defined as the following:

creatinine clearance (as estimated by cockcroft gault or schwartz) ≥ 60 ml/min
serum alt/ast ≤ 5 uln
total bilirubin ≤1.5 x uln except in individuals with gilbert's syndrome
left ventricular shortening fraction(lvsf) ≥ 30% or left ventricular ejection fraction (lvef) ≥ 50%, as determined by echo or muga, no evidence of pericardial effusion (except trace or physiological) as determined by an echo, and no clinically significant arrhythmias
baseline oxygen saturation > 92% on room air

key exclusion criteria for the nhl cohort

history of malignancy other than nonmelanoma skin cancer, carcinoma in situ (eg, cervix, breast), or follicular lymphoma (fl) unless disease free for at least 3 years
prior cd19 targeted therapy other than blinatumomab
history of severe, immediate hypersensitivity reaction attributed to aminoglycosides
presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring iv antimicrobials for management.
history of hiv infection or acute/chronic active hepatitis b or c infection. individuals with a history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing per current infectious diseases society of america guidelines or applicable country guidelines
acute gvhd grade ii-iv by glucksberg criteria or severity b-d by international bone marrow transplant registry (ibmtr) index; acute or chronic gvhd requiring systemic treatment within 4 weeks prior to enrollment.

cns involvement and abnormalities:

any cns tumor mass and/or parameningeal mass (cranial and/or spinal) by imaging with current or prior history of neurological symptoms within 3 months prior to screening.

note: cns involvement without neurologic symptoms will be allowed.

history or presence of any cns disorder such as a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, any autoimmune disease with cns involvement, posterior reversible encephalopathy syndrome (pres), or cerebral edema with confirmed structural defects by appropriate imaging. history of stroke or transient ischemic attack within 12 months before enrollment. individuals with seizure disorders requiring active anti-convulsive medication.

history of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment
primary immunodeficiency
history of severe immediate hypersensitivity reaction to any of the agents used in this study
live vaccine ≤ 6 weeks prior to planned start of lymphodepleting chemotherapy regimen
individuals of both genders of child-bearing potential who are not willing to use a birth control considered to be highly effective per protocol from the time of consent through 6 months after the completion of conditioning chemotherapy or brexucabtagene autoleucel (kte-x19) infusion, whichever is longer.
prior medication:
prior cd19 directed therapy (other than blinatumomab), including car+ t cell, bite, and adc, with the exception of individuals who received brexucabtagene autoleucel (kte-x19) in this study and are eligible for re-treatment
treatment with alemtuzumab within 6 months prior to leukapheresis, or treatment with clofarabine or cladribine within 3 months prior to leukapheresis
dli within 28 days prior to enrollment
any drug used for gvhd within 4 weeks prior to enrollment

note: other protocol defined inclusion/exclusion criteria may apply.",1,1,1,0,0,0,0.0,21.0,Pleura,Pleura,0,0,All
43,43,43,373,NCT02625961,2023-11-08,study of pembrolizumab (mk-3475) and pembrolizumab with other investigational agents in participants with high risk non-muscle invasive bladder cancer (mk-3475-057/keynote-057),a phase ii clinical trial to study the efficacy and safety of pembrolizumab (mk-3475) and pembrolizumab in combination with other investigational agents in subjects with high risk non-muscle-invasive bladder cancer (nmibc) unresponsive to bacillus calmette-guerin (bcg) therapy,,interventional,"in this study, participants with high risk non-muscle-invasive bladder cancer (nmibc) unresponsive to bacillus calmette guerin (bcg) therapy and who are considered ineligible for or have refused to undergo radical cystectomy, will receive pembrolizumab therapy or pembrolizumab in combination with other investigational agents. the primary study hypothesis is that treatment with pembrolizumab will result in a clinically meaningful response.","inclusion criteria:

histologically-confirmed diagnosis of high risk non-muscle-invasive (t1, high grade ta and / or carcinoma in situ [cis]) transitional cell carcinoma of the bladder (mixed histology tumors allowed if transitional cell histology is predominant histology).
fully resected disease at study entry (residual cis acceptable)
bcg-unresponsive high risk non-muscle-invasive bladder cancer after treatment with adequate bcg therapy
ineligible for radical cystectomy or refusal of radical cystectomy
available tissue from a newly obtained core biopsy of a tumor lesion not previously irradiated
eastern cooperative oncology group (ecog) performance status of 0, 1, or 2
adequate organ function
female participants of childbearing potential have a negative urine or serum pregnancy test and must be willing to use an adequate method of contraception
male participants must be willing to use an adequate method of contraception

exclusion criteria:

centrally assessed muscle-invasive, locally advanced nonresectable, or metastatic urothelial carcinoma (i.e., t2, t3, t4, and / or stage iv)
centrally assessed concurrent extra-vesical (i.e., urethra, ureter, or renal pelvis) non-muscle invasive transitional cell carcinoma of the urothelium
currently participating or has participated in a study of an investigational agent and received study therapy or received investigational device within 4 weeks prior to the first dose of study treatment
received intervening intravesical chemotherapy or immunotherapy from the time of most recent cystoscopy / transurethral resection of bladder tumor (turbt) to starting study treatment
received prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to starting study treatment or not recovered from adverse events due to a previously administered agent
known additional malignancy that is progressing or requires active treatment excepting basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. a history of prostate cancer that was treated with definitive intent (surgically or through radiation therapy) is acceptable provided that the following criteria are met: stage t2n0m0 or lower; gleason score ≤7 and prostatic-specific antigen (psa) undetectable for at least 1 year while off androgen deprivation therapy that was either treated with definitive intent or untreated in active surveillance that has been stable for the past year prior to study allocation
active autoimmune disease that has required systemic treatment in the past 2 years
evidence of interstitial lung disease or active non-infectious pneumonitis
active infection requiring systemic therapy
pregnant or breastfeeding, or expecting to conceive within the projected duration of the trial through 120 days after the last dose of study treatment
prior therapy with an anti-programmed cell death 1 (pd-1), anti-pd-ligand 2 (l2) agent, or with an agent directed to another co-inhibitory t-cell receptor
known human immunodeficiency virus (hiv)
known active hepatitis b or c infection
received a live virus vaccine within 30 days of planned start of study treatment
has had an allogeneic tissue/solid organ transplant",1,0,1,0,0,0,18.0,200.0,Bladder,Bladder,0,0,All
44,44,44,377,NCT02628067,2023-11-02,study of pembrolizumab (mk-3475) in participants with advanced solid tumors (mk-3475-158/keynote-158),a clinical trial of pembrolizumab (mk-3475) evaluating predictive biomarkers in subjects with advanced solid tumors (keynote 158),,interventional,"in this study, participants with multiple types of advanced (unresectable and/or metastatic) solid tumors who have progressed on standard of care therapy will be treated with pembrolizumab (mk-3475).","inclusion criteria:

- histologically or cytologically-documented, advanced solid tumor of one of the following types:

anal squamous cell carcinoma
biliary adenocarcinoma (gallbladder or biliary tree (intrahepatic or extrahepatic cholangiocarcinoma) except ampulla of vater cancers)
neuroendocrine tumors (well- and moderately-differentiated) of the lung, appendix, small intestine, colon, rectum, or pancreas
endometrial carcinoma (sarcomas and mesenchymal tumors are excluded)
cervical squamous cell carcinoma
vulvar squamous cell carcinoma
small cell lung carcinoma
mesothelioma
thyroid carcinoma
salivary gland carcinoma (sarcomas and mesenchymal tumors are excluded)
any advanced solid tumor, with the exception of colorectal carcinoma (crc), which is microsatellite instability (msi)-high (msi-h) or
any advanced solid tumor (including colorectal carcinoma [crc]) which is mismatch repair deficient (dmmr)/msi-h in participants from mainland china who are of chinese descent. (crc participants will have a histologically proven locally advanced unresectable or metastatic crc which is dmmr/msi-h that has received 2 prior lines of therapy) or
any advanced solid tumor that has failed at least one line of therapy and is tmb-h (≥10 mut/mb, f1cdx assay), excluding dmmr/msi-h tumors.

note: for participants to be eligible for enrollment they must have failed at least one line of standard of care systemic therapy (ie, not treatment naïve), with the exception of crc participants who must have failed at least 2 lines of standard of care systemic therapy, as per crc specific eligibility criteria. participants must not have melanoma or nsclc.

progression of tumor or intolerance to therapies known to provide clinical benefit. there is no limit to the number of prior treatment regimens
can supply tumor tissue for study analyses (dependent on tumor type)
radiologically-measurable disease
performance status of 0 or 1 on the eastern cooperative oncology group (ecog) performance scale within 3 days prior to first dose of pembrolizumab
life expectancy of at least 3 months
adequate organ function
female participants of childbearing potential must be willing to use adequate contraception during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. the length of time required to continue contraception for each study intervention is as follows: mk-3475 (120 days)

exclusion criteria:

currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study treatment
diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
active autoimmune disease that has required systemic treatment in the past 2 years
prior anti-cancer monoclonal antibody (mab) within 4 weeks prior to study day 1 or not recovered from an adverse event caused by mabs administered more than 4 weeks earlier
prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks of study day 1 or not recovered from adverse events caused by a previously administered agent
known additional malignancy within 2 years prior to enrollment with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or curatively resected in situ cancers
known active central nervous system (cns) metastases and/or carcinomatous meningitis
has known glioblastoma multiforme of the brain stem
has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
active infection requiring systemic therapy
known psychiatric or substance abuse disorders that would interfere with the participant's ability to cooperate with the requirements of the study
pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment
previously participated in any other pembrolizumab (mk-3475) study, or received prior therapy with an anti-programmed cell death (pd)-1, anti-pd-ligand 1 (anti-pd-l1), anti-pd-ligand 2 (anti-pd-l2), or any other immunomodulating mab or drug specifically targeting t-cell co-stimulation or checkpoint pathways
known history of human immunodeficiency virus (hiv)
known active hepatitis b or c
received live vaccine within 30 days of planned start of study treatment
has severe hypersensitivity (≥grade 3) to pembrolizumab and/or any of its excipients
known history of active tuberculosis (tb, bacillus tuberculosis)
has had an allogenic tissue/solid organ transplant.",1,0,1,0,0,0,18.0,200.0,Pleura,Pleura,0,0,All
45,45,45,379,NCT02630368,2022-02-01,a study of metronomic cp and jx-594 in patients with advanced breast cancer and advanced soft-tissue sarcoma (metromajx),a phase i/ii study of metronomic cyclophosphamide and oncolytic poxvirus jx-594 in patients with advanced hormone-receptor positive and triple negative breast cancer and advanced soft tissue sarcoma (metromajx),METROmaJX,interventional,"assessment of the efficacy and safety of jx-594 and metronomic cyclophosphamide in patients with advanced soft-tissue sarcoma and advanced breast cancer, once the maximum tolerated dose have been determined (phase i trial).

phase i study: this is a prospective open-labeled phase i trial based on a dose escalating study design assessing two dose levels of jx594 when prescribed in combination with metronomic cyclophosphamide.

phase ii trials with two treatments strategies:

metronomic cp + jx-594: phase ii study sarcoma: this is a monocentric, randomized two-arm non comparative phase 2 study assessing efficacy and safety of jx-594 in association with metronomic cyclophosphamide in patients with advanced soft-tissue sarcoma.

metronomic cp + jx-594: phase ii study breast cancer: this is a monocentric, single-arm phase ii study, assessing efficacy and safety of jx-594 in association with metronomic cyclophosphamide in patients with advanced breast cancer.

metronomic cp + jx-594 + avelumab: phase ii study sarcoma: this is a monocentric, single arm phase ii study assessing efficacy and safety of avelumab in combination with it jx-594 and metronomic cyclophosphamide in patients with advanced soft-tissue sarcoma.

metronomic cp + jx-594 + avelumab:: phase ii study breast cancer: this is a monocentric, single-arm phase ii study, assessing efficacy and safety of avelumab in combination with it jx-594 and metronomic cyclophosphamide in patients with advanced breast cancer.","main inclusion criteria:

histology:

phase ib : patient with histologically confirmed solid tumor

phase ii :

patients with histologically confirmed her2 negative breast cancer (treatment by cp+jx-594), or triple negative (treatment by avelumab + cp+jx-594)
patients with histologically confirmed soft tissue sarcoma confirmed by the rreps network, b)progressive disease or relapse, after standard therapy according to recist v1.1 criteria diagnosed on the basis of two ct scan or mri obtained at an interval less than 6 months in the period of 12 months prior to inclusion and confirmed by central review
metastatic or unresectable locally advanced disease
age ≥ 18 years
ecog ≤ 1 (phase ib), ≤ 2 (phase ii jx+cp) and ≤ 1 (phase ii avelumab+jx+cp).
life expectancy > 3 months,
measurable disease according to recist v1.1 outside any previously irradiated field. for patients treated by avelumab+jx+cp, at least one injectable site ≥ 2 cm and ≤ 8 cm in diameter and one distant non-injected measurable site (target site)
at least three weeks since last chemotherapy, immunotherapy or any other pharmacological treatment and/or radiotherapy.
adequate hematological, renal, metabolic and hepatic functions.
women of childbearing potential must have a negative serum pregnancy test before study entry. both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for six months after discontinuation of treatment.
patients informed of risks regarding drug interactions: patients receiving any substances that are inhibitors or inducers of cyp450 2b6 are ineligible
voluntarily signed and dated written informed consent prior to any study specific procedure.
patients with a social security in compliance with the french law.

main exclusion criteria:

previous treatment with jx-594 or other vaccina vector based treatment .

concomitant diseases/conditions (non exhaustive list):

clinically significant immunodeficiency, such as hiv or active hepatite b or c
any other major illness that, in the investigator's judgment, will substantially increase the risk associated with the patient's participation in this study.
history of severe exfoliative skins condition requiring systemic treatment for more than 4 weeks in the last two years.
active autoimmune disease for patients treated by avelumab
active central nervous system metastasis (cns)
participation to a study involving a medical or therapeutic intervention in the last 30 days.
previous enrolment in the present study.
patient unable to follow and comply with the study procedures because of any geographical, social or psychological reasons.
known hypersensitivity to any involved study drug or any of its formulation components.
use of steroids (any route of administration), interferon/pegylated interferon or ribavirin that cannot be discontinued within 14 days prior to any jx-594 dose.
no prior malignancy except for the following: adequately treated basal or squamous cell skin cancer, in situ cervical cancer, adequately treated stage 1 or stage 2 cancer from which the patient is currently in complete remission or any other cancer from which the patient has been disease-free for 3 years.
active cardiovascular disease, including but not limited to significant coronary artery disease (e.g. requiring angioplasty or stenting) or congestive heart failure within the preceding 12 months. (treatment by cp+jx)
inability to suspend treatment with anti-hypertensive medication for 48 hours prior to and 48 hours after all jx-594 treatments.
pulse oximetry o2 saturation < 90% at rest on room air.
experienced a severe systemic reaction or side-effect as result of previous smallpox vaccination.
cardiac disease: lvef out of normal limits ; cumulative dose of anthracyclines in excess of 450 mg/m²
known urinary tract obstruction
household contact exclusions for patients enrolled: children< 1 year old ; people with skin disease (e.g., eczema, atopic dermatitis and related diseases…), immunocompromised hosts (severe deficiencies in cell-mediated immunity, including aids, organ transplant recipients, hematologic malignancies)
vaccination within 4 weeks of the first dose of study treatment and while on trial is prohibited except for administration of inactivated vaccines.",1,1,1,0,0,0,18.0,200.0,Breast,Breast,0,1,All
46,46,46,387,NCT02651948,2023-08-18,"transperineal, mri-guided, prostate biopsy","transperineal, mri-guided, prostate biopsy: first step to focal treatment of prostate cancer",,interventional,"primary purpose:

complications and rehospitalizations after transperineal prostate biopsy mri-guided are reduced than transrectal prostate biopsies.

secondary purposes:

patients tolerance after transperineal prostate biopsy mri-guided is better than after transrectal prostate biopsies.
core of transperineal prostate biopsies are better than core of transrectal prostate biopsies
study of correlation between radiologic images and anatomopathologic result
description of needle track during the procedure
description of real time template saturation prostate biopsy
comparison of transperineal prostate biopsy relevance according to ebm
comparison of 1.5t mri and 3t mri for prostate cancer detection","inclusion criteria:

men
40 to 80 years' old
affiliation to french social health system
signed consent
prostate cancer suspicion based on prostate specific antigen (psa) or digital rectal exam with abnormal mri (prostate imaging reporting and data system score 3) and negative transrectal prostate biopsies
patient treated by active surveillance for a low risk prostate cancer (t1c or t2a, gleason = 6, psa < 10)

exclusion criteria:

gleason > 6 prostate cancer
metastatic prostate cancer
contraindication to mri
contraindication to general anesthesia
non-reversible hemostasis trouble
inability to give consent",1,0,0,0,1,0,40.0,80.0,Prostate,Prostate,1,0,Male
47,47,47,388,NCT02653105,2020-03-23,women at risk of breast cancer and olfm4,"evaluation of the circulating concentration of olfactomédine 4 (olfm4) in women with a brca1 or 2 gene mutation or at high risk of developing breast cancer, according to the imaging",,interventional,does the olfactomédine provide an help to limit the number of false positives in the overall imaging balance and limit the number of unnecessary biopsies?,"inclusion criteria:

age > or = 18 years

high risk women of breast cancer occurrence defined by the following criteria:

women carrying a genetic mutation brca1 or 2 or tp53, entering or already in screening breast irm
women with a high probability of hereditary predisposition to breast cancer (20% risk at 70 years of breast cancer by boadicea model), assessed by the onco-geneticists
information of the person and signing the informed consent

exclusion criteria:

women with a history of breast cancer or in situ
person who is not affiliated to a social security scheme or beneficiary of such a regime",1,0,0,0,0,1,18.0,200.0,Breast,Breast,0,1,Female
48,48,48,404,NCT02678091,2022-08-10,ultrasound exam with doppler for the etiological diagnosis of orbital masses (puce),contribution of the quantitative analysis of the ultrasound exam with doppler for the etiological diagnosis of orbital masses (puce),PUCE,interventional,"orbital masses develop at the expense of the orbital structures lacrimal glands, oculomotor muscles, optic nerve, meningeal spaces, peripheral nerves, bone wall, orbital fat, lymphoid structures or vascular structures. these masses can be tumors, benign or malignant, or pseudotumor, mainly represented by specific or non-specific orbital inflammation.

pathology is of considerable importance for the diagnosis and the treatment of those masses. however, biopsy or surgical resection of the orbital masses is sometimes difficult and dangerous outside expert centers.

the identification of a non-invasive technique for distinguishing tumors from pseudotumors, thus avoid in some cases a biopsy, would be a major contribution for the patients.

quantitative analysis of the ultrasound exam with doppler of those masses could identify diagnostic criteria, especially for the lacrimal gland, easily explorable.","inclusion criteria:

patient aged 18 years or more
with an orbital mass for which a biopsy and/or a surgical removal is planned
before surgery or biopsy

exclusion criteria:

pregnancy
breast feeding
patient under a legal protection procedure
patient denying to participate to the study
lack of affiliation to a social security system",1,0,0,0,0,1,18.0,200.0,Pleura,Pleura,0,1,All
49,49,49,417,NCT02715284,2023-08-18,"study of tsr-042, an anti-programmed cell death-1 receptor (pd-1) monoclonal antibody, in participants with advanced solid tumors","a phase 1 dose escalation and cohort expansion study of tsr-042, an anti-pd-1 monoclonal antibody, in patients with advanced solid tumors",GARNET,interventional,"this is a multi-center, open-label, first-in-human phase 1 study evaluating the anti-programmed death receptor 1 (anti-pd-1) antibody dostarlimab (also known as tsr-042) n participants with advanced solid tumors who have limited available treatment options. the study will be conducted in 2 parts with part 1 consisting of safety evaluation, pharmacokinetics (pk), and pharmacodynamics (pdy) of escalating doses of dostarlimab. dose escalation will be based on ascending weight-based dose levels (dls) of dostarlimab and will continue until the maximum tolerated dose (mtd) is reached or may be stopped at any dose level up to the highest dose of 20 milligrams per kilograms (mg/kg) based on emerging safety and pk/pdy data. part 2 will be conducted in two subparts, part 2a (fixed-dose safety evaluation cohorts) and part 2b (expansion cohorts). part 2a of the study will evaluate the safety and tolerability of dostarlimab at fixed doses of 500 mg administered every 3 weeks (q3w) and 1000 mg administered every 6 weeks (q6w). part 2b of the study will examine the safety and clinical activity of dostarlimab in cohorts of participants with specific types of advanced solid tumors.","inclusion criteria:

participant is at least 18 years of age.
participant has proven recurrent or advanced solid tumor and has disease progression after treatment with available anti cancer therapies, or is intolerant to treatment that meets the following requirements for the part of the study they will participate in:
a. part 1: any histologically or cytologically proven recurrent advanced solid tumor
b. part 2a: : any histologically or cytologically proven recurrent advanced solid tumor
c. part 2b: histologically of cytologically proven recurrent or advanced solid tumor with measurable lesion(s) per recist version 1.1 and meets one of the following disease types:
the criteria below should be met for participant participating in: cohort a1 (dmmr/msi-h endometrial cancer) and cohort a2 (mmr-proficient/mss endometrial cancer)
participants who have progressed on or after platinum doublet therapy
participants have received no more than 2 lines of anti-cancer therapy for recurrent or advanced (>=stage iiib) disease. prior treatment with hormone therapies is acceptable and does not count towards the number of anti-cancer therapies noted in the criterion above for this cohort.
all endometrial cancer histologies are allowed except endometrial sarcoma (including carcinosarcoma).
participants must submit 2 scans demonstrating increase in tumor measurement that meet criteria for pd on or after the latest systemic anti-cancer therapy based on recist version 1.1 to central radiology prior to the first dose of dostarlimab.
presence of at least 1 measurable lesion on baseline scan will be confirmed by central radiology review.
status of tumor mmr/msi: participants can be screened based on local mmr/msi testing results using immunohistochemistry (ihc), polymerase chain reaction (pcr), or next generation sequencing (ngs) performed in a certified local laboratory, but participant eligibility needs to be determined by mmr ihc results. for participant with available local mmr ihc results for the respective cohort(s), tumor samples have to be submitted to a central ihc laboratory and its quality has to be checked and cleared prior to cycle 1 day 1 (c1d1). for participants without available local mmr ihc test results (participants with local pcr or ngs test results), central ihc results have to confirm eligibility prior to proceeding with other screening procedures. after the central ihc test is completed, remaining tumor tissue may be tested for further exploratory biomarkers or may be sent to a central ngs laboratory for further testing.
cohort e - participants with nsclc who progressed after at least 1 prior platinum-based systemic chemotherapy regimen for recurrent or advanced disease. chemotherapy regimen in the adjuvant or neoadjuvant setting following surgery and/or radiation is acceptable if recurrent or advanced disease develops within 6 months from completion of therapy.
participants with a known epidermal growth factor receptor (egfr) mutation must have received a chemotherapy regimen and an egfr tyrosine-kinase inhibitor (tki) (e.g., erlotinib, gefitinib, afatinib, or experimental)
participants with a known anaplastic lymphoma kinase (alk) translocation must have received a chemotherapy regimen and an alk inhibitor (e.g., crizotinib, ceritinib or experimental)
cohort f - participants with recurrent or advanced dmmr/msi-h solid tumors except endometrial cancers and gastrointestinal cancers, who have received prior systemic therapy and who have no alternative treatment options. prior treatment with hormone therapies alone given for recurrent or advanced disease is acceptable and does not count towards the number of anti-cancer therapies.
measurable lesion by recist 1.1 radiology on baseline scan will be confirmed by central radiology review prior to first dose of dostarlimab. patients with primary cns tumor should provide brain mri at baseline.
a. presence of deficient mismatch repair (dmmr) and/or microsatellite instability (msi-h) in the tumor defined by either:
b. deficient dna mismatch repair (dmmr); mmr status must be assessed by immunohistochemistry (ihc) for mmr protein expression (mlh1, msh2, msh6, pms2) where loss of one or more proteins indicates dmmr; dmmr may be determined either locally or by the central reference lab; or
c. microsatelillite instability (msi-h); msi-h as determined by polymerase chain reaction (pcr) or by tissue next generation sequencing (ngs); msi-h may be determined locally
cohort g: participants must have recurrent high-grade serous, endometrioid, or clear cell ovarian, fallopian tube, or primary peritoneal cancer. participants must have presence of at least 1 measurable lesion on baseline scan that will be confirmed by central radiology review.
participants must be considered resistant to the last administered platinum therapy, that is, the time from the last administered platinum dose until the initial documented progression (as evidenced by radiographic progression per recist version 1.1) must be less than 6 months.
participants must have completed at least 1 but no more than 3 prior lines of therapy for advanced or metastatic ovarian cancer. neoadjuvant, adjuvant, and the combination of both will be considered as 1 line of therapy. treatment with single-agent bevacizumab given as maintenance is not counted as a separate line of therapy. if a therapeutic regimen is modified or changed for a reason other than lack of response or pd (such as allergic reaction, toxicity, or drug availability), this is not counted as a separate line of therapy. the use of single-agent hormonal therapy given for reasons other than pd per recist version v1.1 (i.e., hormonal therapy given for increasing cancer antigen [ca]-125 levels) is not counted as a separate line of therapy.
participants must have been previously treated with platinum-based regimen, taxane agent(s), and bevacizumab (bevacizumab could be used as a single agent or in combination with another agent, in frontline therapy, as maintenance, or for treatment of recurrent disease).
part 2b: participants must have archival tumor tissue available that is formalin-fixed and paraffin-embedded (ffpe).
for participants who do not have archival tissue, a new biopsy must be performed to obtain a tissue sample prior to study treatment initiation. for participants without available archival tissue, the biopsy should be taken from the tumor lesions (either primary or metastatic) that have easy accessibility and low biopsy-associated risks and will exclude biopsies of the liver, brain, lung/mediastinum, pancreas, or endoscopic procedures extending beyond the esophagus, stomach or bowel.
for cohort f an ffpe tissue sample must be submitted to the central laboratory for testing. for patients with available local mmr/msi-h results, tumor samples have to be submitted to a central laboratory and its quality has to be checked and cleared prior to c1d1
for cohort g, participant must provide formalin fixed paraffin embedded (ffpe) tumor tissue block(s) with sufficient tumor content (as confirmed by the sponsor's designated central laboratory) during screening to enable, for example, measures of homologous recombination pathway defects and pd-l1 status. the use of slides created from paraffin-embedded tissue as opposed to ffpe blocks must be approved by the sponsor.
female participants must have a negative serum pregnancy test within 72 hours prior to the date of the first dose of study medication: unless they are of non-child bearing potential.
non child bearing potential is defined as: >= 45 years of age and has not had menses for > 1 year; amenorrheic for < 2 years without a hysterectomy and oophorectomy and have a follicle- stimulating hormone (fsh) value in the postmenopausal range upon pre-study (screening) evaluation. post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound, magnetic resonance imaging (mri) or computed tomography (ct) scan. tubal ligation must be confirmed with medical records of the actual procedure.
female participants of childbearing potential must agree to use 1 highly effective form of contraception with their partner starting with the screening visit through 150 days after the last dose of study therapy.
participant has an eastern cooperative oncology group (ecog) performance status of <= 2 for part 1 and <= 1 for part 2.
participant has an adequate organ function.

exclusion criteria

participant has received prior therapy with an anti- programmed death receptor 1 (anti-pd-1), anti-pd-1- ligand-1 (anti-pd-l1), or anti-pd-1 ligand-2 (anti-pd- l2) agent.
participant has a known uncontrolled central nervous system (cns) metastases and/or carcinomatous meningitis.
participant has a known additional malignancy that progressed or required active treatment within the last 2 years. exceptions include basal cell carcinoma of the skin, squamous cell cancer (sqcc) of the skin that has undergone potentially curative therapy, or in situ cervical cancer, or other neoplastic condition which has undergone curative therapy and is considered cured by the investigator.
participant is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease or active infection requiring systemic therapy. specific examples include, but are not limited to, active, non-infectious pneumonitis; uncontrolled ventricular arrhythmia; recent (within 90 days) myocardial infarction; uncontrolled major seizure disorder; unstable spinal cord compression; superior vena cava syndrome; or any psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study (including obtaining informed consent).
participant is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study, starting with the screening visit through 150 days after the last dose of study treatment.
participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
participant has a known history of human immunodeficiency virus (hiv) (hiv 1/2 antibodies).
participant has a known active hepatitis b (eg, hepatitis b surface antigen [hbsag] reactive) or hepatitis c (eg, hepatitis c virus ribonucleic acid (hcv rna) (qualitative) is detected).
participant has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease- modifying agents, corticosteroids, or immunosuppressive drugs). replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. use of inhaled steroids, local injection of steroids, and steroid eye drops are allowed.
participant has as history of interstitial lung disease.
participant has not recovered (i.e., to <= grade 1 or to baseline) from radiation- and chemotherapy-induced aes or received transfusion of blood products (including platelets or red blood cells) or administration of colony-stimulating factors (including granulocyte-colony stimulating factor [g-csf], granulocyte macrophage colony-stimulating factor [gm-csf] or recombinant erythropoietin) within 3 weeks prior to the first dose of study drug.
participant has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to the first dose of study drug.
participant has received prior anti-cancer therapy (chemotherapy, targeted therapies, radiotherapy, or immunotherapy) within 21 days, or less than 5 times the half-life of the most recent therapy prior to study day 1, whichever is shorter.
participant has not recovered adequately (<= grade 1) from aes and/or complications from any major surgery prior to starting therapy.
participant has received a live vaccine within 14 days of planned start of study therapy.
participant has a known hypersensitivity to dostarlimab components or excipients.
for cohort g, participants will not be eligible if they meet the following criteria: participants who experienced disease progression within 3 months (as evidenced by radiographic progression per recist) of first-line platinum therapy.
participants with known deleterious or suspicious deleterious mutation in brca1 or brca2 genes (local testing permitted).
participants has received prior therapy with a poly(adenosine diphosphate-ribose) polymerase (parp)-1/parp-2 inhibitor.
participant has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, might interfere with the participant's participation for the full duration of the study treatment, or is not in the best interest of the participant to participate.
participant is immunocompromised. participants with splenectomy are allowed.",1,1,0,0,0,0,18.0,200.0,Pleura,Pleura,0,0,All
50,50,50,418,NCT02716233,2019-02-18,a french protocol for the treatment of acute lymphoblastic leukemia (all) in children and adolescents,a french protocol for the treatment of acute lymphoblastic leukemia (all) in children and adolescents,CAALL-F01,interventional,"a still major question in the field of acute lymphoblastic leukemia (all) in children - an extremely heterogeneous disease though curable in 80-90% of children and 70-80% of the adolescents - is the optimal use of l-asparaginase (asnase). it is known that administering asnase results in the depletion of asparagine circulating in the blood, which starves the leukemic cells and results in their death. but indeed the use of asnase varies between protocols considering the different brands, the dose and the administration modalities. oncaspar (pegylated e. coli asparaginase, pegaspargase) was thus developed with the goal of reducing the immunogenicity of the native asnase.

this is a french prospective multicentric cohort study of children and adolescents with all, stratified on (i) the type of all ( b vs t) and (ii) the anticipated risk (stratified in 3 groups for childhood b-cell precursor (bcp)-all and 2 groups for t-cell all).

it aims to answer to two different issues:

randomized question: what is the best way to administer pegaspargase? a cohort of children and adolescents with standard or medium risk all will be randomized to receive during induction either one infusion of oncaspar® 2500 iu/m2 at d12 or two infusions of oncaspar® at 1250 iu/m2 each at d12 and d26. patients will then receive 2500 iu/m2 or 1250 iu/m2 per dose during consolidation and delayed intensification according to the initial arm of randomization.
non randomized question: in the high/very high risk groups, a non randomized intensification of the scheme of asparaginase administration is proposed during induction therapy: 2 infusions of 2500 iu/m2/day (d12 and d26) will be administered. all patients will receive 2500 iu/m2 per dose during consolidation and delayed intensifications.","inclusion criteria:

all l1 or l2
b-lineage or t- lineage all

exclusion criteria:

l3 (burkitt's leukemia)
mixed phenotype acute leukemia (who criteria).
infant all (age ≤ 365 days)
philadelphia (ph)+/breakpoint cluster region (bcr)-abelson (abl) all",1,0,0,1,0,0,1.0,18.0,Pleura,Pleura,0,0,All
51,51,51,426,NCT02735057,2022-05-31,chemoradiotherapy in elderly patients with oesophagus cancer,phase i-ii study chemoradiation in elderly patients with oesophagus cancer,OSAGE,interventional,"management of elderly patient with cancer is a therapeutic challenge and a public health problem. the mean age of esophageal cancer is 64.5 years and 72.1 years in men and women respectively. surgery is a standard treatment reserved to about 30 % of patients. the other 70 % are considered unfit for surgery for various reasons, including ageing.

chemoradiotherapy (crt) is standard treatment for patients with esophageal cancer unfit for surgery. the validated treatment scheme is external beam radiotherapy (ebrt) 50 gy over 5 weeks combined with cisplatin and 5fu infusion. however it induces high rates of severe and life threatening toxicities: grade 3 haematologic and esophageal mucositis of 20 and 25 % respectively, in patients with a median age of 64 years. crt has not been properly evaluated in patients more than 75 years, and other combined chemotherapy are challenging.","inclusion criteria:

esophageal cancer, squamous and adenocarcinoma types, t1-3, n0-1, m1a (tnm 6th),
age > 75 years,
who status < 2, balducci 1, adequate bone marrow reserve, normal renal and hepatic function.

exclusion criteria:

age < 75 years",1,1,1,0,0,0,75.0,100.0,Pleura,Pleura,0,0,All
52,52,52,449,NCT02785757,2021-01-05,cancer-related thromboembolic disease,the challenge of cancer-related thromboembolic disease: can we better predict the risk?,PROSPECT,interventional,"patients with cancer are at particularly high risk of venous thromboembolism (vte). the guidelines therefore strongly recommend thromboprophylaxis but recent surveys clearly show that oncologists are reluctant to use it because of concern over bleeding, absence of validated risk stratification tools and uncertainties concerning the optimal thromboprophylaxis. hence, it is a real challenge to identify the individual vte risk of each cancer patient and individually tailor their thromboprophylaxis.

the study aims to identify thrombin generation test (tgt) as a reliable, standardized overall haemostasis assay that can be used to evaluate individual thrombosis risk

the secondary objectives are:

to define the limits of tgt parameters that indicate thrombosis risk in cancer patients
to evaluate values of other clotting activation markers in patients with cancer

patients recently diagnosed with locally advanced or metastatic adenocarcinoma of any origin, who are scheduled for systemic chemotherapy, will be enrolled in the trial at baseline (visit 1). thrombin generating capacity will be measured within the first month following diagnosis and before the start of the chemotherapy (between visit 1 and visit 2) and subsequently at the end of the first cure line of chemotherapy (visit 3). patients will be followed up for a period of 1 year, or until the occurrence of a thromboembolic event. two follow up visits are foreseen - 6-month (visit 4) and 12-month (or at the end of trial - visit 5) visits.

patients eventually undergoing second-line chemotherapy during the course of the follow-up will remain on study.

the study will document all cases of symptomatic thromboembolic events together with the relevant diagnostic work-up.","inclusion criteria:

adult patients of both sexes with locally advanced or metastatic adenocarcinoma of any origin, who are scheduled for systemic chemotherapy
subjects having signed informed consent prior to initiation of any study procedure
covered by a health system

exclusion criteria:

known bleeding or thrombophilia disorders
eastern cooperative oncology group (ecog) performance status ≥ 3
patient immobilized
confirmed venous thromboembolism in the last 12 months
active bleeding or bleedings in the last 4 weeks requiring hospitalization, transfusion, or surgical intervention
anticoagulant therapy at the moment of first sampling (at least one day off for heparines and doac; at least 5 days off for vka is needed)
antiplatelet therapy at the moment of first sampling (only if prp tga can be performed at site)
severe hepatic insufficiency
life expectancy of less than 3 months
pregnancy",1,0,0,0,0,1,18.0,200.0,Pleura,Pleura,0,0,All
53,53,53,450,NCT02785861,2016-05-30,step by step after cancer,evaluating the effectiveness of supervised practice or distance supervised physical activity (walking) in the overall management of fatigue in breast cancer patients during hormonal therapy: pilot study,SBSAC,interventional,"after treatment, women want to regain a 'normal' lifestyle while some factors interfere as chronic fatigue. in the absence of anemia, fatigue is often a consequence of physical deconditioning . the following protocol will focus at this problem.it will consist of a brisk walking program twice a week over a period of 6 weeks, at an intensity of 60% of hr pic during 20 minutes.","inclusion criteria:

sex: female
age less than or equal to 75 years
breast cancer stage i to iii
chemotherapy and / or radiotherapy adjuvant completed
hormone treatments ongoing

exclusion criteria:

age over 75 years
breast cancer stage iv and o
anemia, cardiac arrhythmia, asthma, hypertension or uncontrolled diabetes, coronary artery disease or severe respiratory disease, psycho-cognitive may disturb walking program",1,0,0,0,0,1,18.0,75.0,Breast,Breast,0,1,Female
54,54,54,453,NCT02789384,2023-03-01,cinsarc signature and correlation with hemotherapy efficacy in soft-tissue sarcomas. a biomarker study.,prognostic value of the cinsarc (complexity index in sarcoma) signature and correlation with chemotherapy efficacy in soft-tissue sarcomas. a biomarker study. (neosarcomics ),NEOSarcomics,interventional,"this is a prospective observational biomarker study including patients with non-metastatic, soft-tissue sarcomas (sts) for whom neoadjuvant chemotherapy is considered as the best option by the multidisciplinary sarcoma team of one of the participating centers.","inclusion criteria:

histologically confirmed soft-tissue sarcoma by central review, except if the diagnosis was already confirmed by the rreps (réseau de référence en pathologie des sarcomes et des viscères) network,
available archived frozen tumor tissue sample or patient consenting to undergo a biopsy of the tumour for research purpose,
non-metastatic disease, for which the use of chemotherapy to ""downstage"" the sarcoma prior to surgery, is assumed to result in better local tumor control by the multidisciplinary sarcoma team of one of the french reference centers involved in this study,
age ≥ 18 years,
eastern cooperative oncology group (ecog) performance status (ps) ≤ 1,
measurable disease according to recist v1.1 outside any previously irradiated field,
neoadjuvant anthracycline-based chemotherapy proposed as the best option by the multidisciplinary sarcoma team of one of the french reference centers involved in this study,
no prior or concurrent malignant disease diagnosed or treated in the last 2 years except for adequately treated in situ carcinoma of the cervix, basal or squamous skin cell carcinoma, or in situ transitional bladder cell carcinoma,
voluntarily signed and dated written informed consents prior to any study specific procedure,
patients with a social security in compliance with the french law relating to biomedical research (article 1121-11 of french public health code).

exclusion criteria:

pathological diagnosis different from a soft-tissue sarcoma,
histological subtypes: well-differentiated liposarcoma, alveolar soft-part sarcoma, dermatofibrosarcoma protuberans, clear-cell sarcoma, rhabdomyosarcoma,
previous treatment for the sarcoma,
contra-indication precluding the administration of chemotherapy as assessed by the investigator,
participation to a study involving a medical or therapeutic intervention in the last 30 days,
previous enrolment in the present study,
pregnant or breast feeding women,
patient unable to follow and comply with the study procedures because of any geographical, social or psychological reasons.",1,0,0,0,0,1,18.0,200.0,Pleura,Other,0,1,All
55,55,55,457,NCT02799212,2023-02-27,evaluation of postoperative ascites after somatostatin infusion following hepatectomy for hepatocellular carcinoma,evaluation of postoperative ascites after somatostatin infusion following hepatectomy for hepatocellular carcinoma: multicenter randomized double-blind placebo controlled trial (somaprotect01),SOMAPROTECT01,interventional,"most patients undergoing hepatectomy for hepatocellular carcinoma (hcc) suffer from underlying liver disease and are exposed to the risk of postoperative ascites, with subsequent morbidity, liver and renal failure, the need for specific treatments and prolonged hospital stay. postoperative ascites is favored by an imbalance between portal venous inflow and the diminished hepatic venous outflow. finding a reversible, non-invasive method for modulating the portal inflow would be of interest: it could be used temporarily during the early postoperative course to prevent acute portal hypertension. somatostatin, a well-known drug already used in several indications, may limit the risk of postoperative ascites and liver failure by decreasing portal pressure after hepatectomy for hcc in patients with underlying liver disease.","inclusion criteria:

patients with hcc diagnosed by histology or by imaging findings according to the barcelona clinic liver cancer group
patients with a single or multiple hccs deemed to be resectable with a curative intent at the preoperative evaluation
patients for whom an indication for hepatectomy has been decided and approved by multidisciplinary board:
by laparotomy
by coelioscopy with resection of at least 2 liver segments
patients with any underlying liver disease with or without proven cirrhosis, regarding histological features (including f2-f3-f4 fibrosis with or without cirrhosis) or with other evidence of a diseased liver if no biopsy has been performed preoperatively (dysmorphic liver or evidence of portal hypertension at imaging findings, oesophageal varices at endoscopy)
age ≥ 18 years
patients with ability to understand and sign a written inform consent form
patients who will be available for follow-up

exclusion criteria:

patients participating in another interventional research in progress or including an exclusion period still in progress at pre-inclusion (except interventional research with minimal risks and constraints that do not interfere with the judgement criteria of the study according to the judgement of the coordinating investigator).
patients with evidence of a healthy liver at biopsy

disease-associated non-inclusion criteria include:

another histologic type of hepatic tumor besides hcc
distant extra-hepatic metastases, including peritoneal carcinomatosis
the existence of complete portal thrombosis of the main portal trunk

operative technique-associated non-inclusion criteria include:

- indication of coelioscopy with resection of less than 2 liver segments",1,0,0,1,0,0,18.0,200.0,Pleura,Pleura,0,0,All
56,56,56,461,NCT02806258,2021-05-10,comparing sequential neoadjuvant treatment including chemotherapy and accelerated radiation focused to the tumor bed vs neoadjuvant chemotherapy alone,"comparing sequential neoadjuvant treatment including chemotherapy and accelerated radiation focused to the tumor bed vs neoadjuvant chemotherapy alone, for triple negative locally advanced breast cancers and luminal b proliferating, inaccessible to a conservative surgery the outset",Néo-APBI-01,interventional,"in the neoapbi 01 trial, the objective is to demonstrate the efficacy of combined apbi and ct administered sequentially in patients with intermediate ad high risk bc. the hypothesis is that combined pst-sequential apbi may increase the rate of pcr, breast conservation and survival without additional toxicity, as seen with wbi","inclusion criteria:

patients ≥ 18 years of age
histologically confirmed invasive carcinoma of the breast
patient who desires breast conservation
tumor stage t1n1, t2-3 n0-1
operable bc for which an indication for ct is determined, including t1n1 and high risk t2-3 n0-1 tumors.
lobular and/or ductal invasive carcinoma
confirmation by imaging (standard +/- mri) of unicentric and unilateral disease
luminal b (defined by hormone receptor positive and grade ii-iii (if available from core biopsy) and ki67 ≥ 15% or by genomic analysis) and tng subtypes
her2 negative
no distant metastases
no contraindication for pst with anthracycline and/or taxane based regimens
patients with no psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
signed informed consent to participate in the study must be obtained from patients after they have been fully informed of the nature and potential risks by the investigator with the aid of written information.

exclusion criteria:

patients considered too frail for ct whatever their age.
breast cancer clinical grade t4 and /or with major nodal involvement n2 (clinically, us, mri or pet-ct).
lumpectomy is considered to be possible with an anticipated favourable cosmetic outcome considering the tumor size/breast size
multicentricity that would not allow bcs as confirmed by breast imaging
uni or bilateral inflammatory (t4d) bc
metastatic disease
other histology types: ciribriform or tubular or mucinous or epideroid carcinomas
her2 positive
no signed consent to participate in the study
previous malignancy (except non melanoma skin cancer, thyroid carcinoma, non-invasive cancers outside the breast and patients with previous cancer in remission since more > 5 years)
patients with psychological, familial, sociological or geographical conditions potentially hampering compliance with the study protocol and follow-up schedule
patients unwilling or unable to comply with the protocol (especially necessity to undergo breast surgery despite clinical complete response)
patients who have received any other investigational drugs within 30 days prior to the screening visit
pregnancy
active connective tissue disease involving the skin
patients with other concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study .",1,1,1,0,0,0,18.0,200.0,Breast,Breast,0,0,Female
57,57,57,463,NCT02807129,2019-10-24,fragmentation of elastin as a biological marker of frailty and impact in tumor progression in elderly patients with cancer,fragmentation of elastin as a biological marker of frailty and impact in tumor progression in elderly patients with cancer,AgElOn,interventional,"the aim of the study is to evaluate frailty in patients aged ≥ 65 years with cancer. the elderly population is very heterogeneous, it is necessary to evaluate these elderly patients before treatment to assess the risk-benefit balance. to date, this assessment relies on subjective clinical methods often not optimal, and slow to implement. an innovative method of evaluation could be the determination of elastin peptides. indeed, the rate of these peptides, which are linked to serious conditions associated with age, rising inexorably with age and dose could help determine more objectively the type of treatment to offer older patients.

expected results : this study will allow better identification of the group of frail elderly through more relevant biological marker that clinical assessment, often subjective and not available within a period compatible with the treatment of newly diagnosed cancer. this biological assessment will also enable optimal management of elderly patients in particular by allowing the geriatrician better efficiency.","inclusion criteria:

65 years or older
diagnosis of cancer
affiliation to a social security scheme
signed informed consent for the study and for the collection of biological samples

exclusion criteria:

patient protected by law (guardianship, trusteeship)",1,0,0,0,0,1,65.0,200.0,Pleura,Pleura,0,0,All
58,58,58,466,NCT02810743,2023-03-21,substantially improving the cure rate of high-risk brca1-like breast cancer,substantially improving the cure rate of high-risk brca1-like breast cancer patients with personalized therapy (subito) - an international randomized phase iii trial,Subito,interventional,"investigator-initiated, international, multicentre, randomized, open-label, (neo)adjuvant phase iii study in target population (stage iii, her2-negative, brca1-like breast cancer patients) comparing optimized standard-dose chemotherapy with intensified, alkylating chemotherapy with stem cell rescue.","inclusion criteria:

women and men with stage iii adenocarcinoma of the breast harboring signs of a breast cancer with features of homologous recombination deficiency (hrd)
age of 18-65 years
the tumor must be her2-negative
treatment must start within 8 weeks after the last surgical resection
eastern cooperative oncology group (ecog) performance status 0-1

exclusion criteria:

previous radiation therapy
previous chemotherapy
any previous treatment with a parp-inhibitor, including olaparib
pre-existing neuropathy from any cause in excess of grade 1
chronic concomitant use of known strong or moderate cyp3a inducers",1,0,0,1,0,0,18.0,65.0,Breast,Breast,1,0,All
59,59,59,469,NCT02813135,2023-05-26,european proof-of-concept therapeutic stratification trial of molecular anomalies in relapsed or refractory tumors,european proof-of-concept therapeutic stratification trial of molecular anomalies in relapsed or refractory tumors,ESMART,interventional,"this proof-of-concept platform trial is designed to cover the targeting of several survival pathways in oncogenesis that are currently not adequately employed for pediatric patients in europe (geoerger 2017; geoerger 2019).

the aims of the trial are:

to determine the recommended phase ii dose (rp2d) of a specific anticancer agent and/or a relevant combination in a pediatric population, to document its tolerability and
to explore first signals of activity in a molecularly enriched study population.","inclusion criteria:

patients must be diagnosed with a haematologic or solid tumor malignancy that has progressed despite standard therapy, or for which no effective standard therapy exists.
age < 18 years at inclusion; patients 18 years and older may be included after discussion with the sponsor if they have a pediatric recurrent/refractory malignancy.
patient must have had advanced molecular profiling (i.e. wes/wgs +/- rnaseq) of their recurrent or refractory tumor i.e. at the time of disease progression/relapse; exceptionally patients with advanced molecular profiling at diagnosis may be allowed.
evaluable or measurable disease as defined by standard imaging criteria for the patient's tumor type (recist v1.1, rano criteria for patients with hgg, inrc criteria for patients with nb, leukemia criteria, etc.).
patients with relapsed or refractory leukemia are eligible for this study.
performance status: karnofsky performance status (for patients >12 years of age) or lansky play score (for patients ≤12 years of age) ≥ 70%. patients who are unable to walk because of paralysis or stable neurological disability, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
life expectancy ≥ 3 months

adequate organ function:

hematologic criteria (leukemia patients are excluded from hematological criteria):

peripheral absolute neutrophil count (anc) ≥ 1000/μl(unsupported)
platelet count ≥ 100,000/μl (unsupported)
hemoglobin ≥ 8.0 g/dl (transfusion is allowed)

cardiac function:

shortening fraction (sf) >29% (>35% for children < 3 years) and left ventricular ejection fraction (lvef) ≥50% at baseline, as determined by echocardiography (mandatory only for patients who have received cardiotoxic therapy).
absence of qtc prolongation (qtc > 450 msec on baseline ecg, using the fridericia correction [qtcf formula]) or other clinically significant ventricular or atrial arrhythmia.

renal and hepatic function:

serum creatinine ≤ 1.5 x upper limit of normal (uln) for age
total bilirubin ≤ 1.5 x uln
alanine aminotransferase (alt)/serum glutamic pyruvic transaminase (sgpt) ≤ 2,5 x uln; aspartate aminotransferase (ast)/serum glutamic oxaloacetic transaminase/sgot ≤ 2,5 x uln except in patients with documented tumor involvement of the liver who must have ast/sgot and alt/sgpt ≤ 5 x uln.
able to comply with scheduled follow-up and with management of toxicity.
females of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to initiation of treatment. sexually active women of childbearing potential must agree to use acceptable and appropriate contraception during the study and for at least 6 months after the last study treatment administration. sexually active males patients must agree to use condom during the study and for at least 6 months (7 months for arm j) after the last study treatment administration. acceptable contraception are defined in ctfg guidelines ""recommendations related to contraception and pregnancy testing in clinical trials""
for all oral medications patients must be able to comfortably swallow capsules (except for those for which an oral solution is available); nasogastric or gastrostomy feeding tube administration is allowed only if indicated.
written informed consent from parents/legal representative, patient, and age-appropriate assent before any study-specific screening procedures are conducted according to local, regional or national guidelines.
patient affiliated to a social security regimen or beneficiary of the same according to local requirements.

exclusion criteria:

patients with symptomatic central nervous system (cns) metastases who are neurologically unstable or require increasing doses of corticosteroids or local cns-directed therapy to control their cns disease. patients on stable doses of corticosteroids for at least 7 days prior to receiving study drug may be included.
impairment of gastrointestinal (gi) function or gi disease that may significantly alter drug absorption of oral drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome).
clinically significant, uncontrolled heart disease (including history of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality, unstable ischemia,congestive heart failure within 12 months of screening)
active viral hepatitis or known human immunodeficiency virus (hiv) infection or any other uncontrolled infection.
presence of any ≥ ctcae grade 2 treatment-related toxicity with the exception of alopecia, ototoxicity or peripheral neuropathy.
systemic anticancer therapy within 21 days of the first study dose or 5 times its half-life, whichever is less.
previous myeloablative therapy with autologous hematopoietic stem cell rescue within 8 weeks of the first study drug dose
allogeneic stem cell transplant within 3 months prior to the first study drug dose. patients receiving any agent to treat or prevent graft-versus host disease (gvhd) post bone marrow transplant are not eligible for this trial.
radiotherapy (non-palliative) within 21 days prior to the first dose of drug (or within 6 weeks for therapeutic doses of mibg or craniospinal irradiation).
major surgery within 21 days of the first dose. gastrostomy, ventriculo-peritoneal shunt, endoscopic ventriculostomy, tumor biopsy and insertion of central venous access devices are not considered major surgery, but for these procedures, a 48 hour interval must be maintained before the first dose of the investigational drug is administered.
currently taking medications with a known risk of prolonging the qt interval or inducing torsades de pointes (refer to appendix 8).
currently taking medications that are mainly metabolized by cyp3a4/5, cyp2c8, cyp2c9, cyp2c19, cyp2d6 or the drug transporters pgp (mdr1), bcrp, oatp1b1, oatp1b3, oct1 and oct2 and have a low therapeutic index that cannot be discontinued at least 7 days or 5 x reported elimination half-life prior to start of treatment with any of the investigational drugs and for the duration of the study (refer to appendix 9).
known hypersensitivity to any study drug or component of the formulation.
pregnant or nursing (lactating) females.
vaccinated with live, attenuated vaccines within 4 weeks of the first dose of study drug.",1,1,1,0,0,0,0.0,18.0,Pleura,Pleura,0,0,All
60,60,60,470,NCT02817958,2022-10-24,evaluation of lymphadenectomy and chemotherapy tip on inguinal lymph nodes in squamous cell carcinoma of the penis,prospective phase ii study evaluating a multimodal care of inguinal node metastasis in squamous cell carcinoma of the penis by bilateral lymphadenectomy and chemotherapy tip,MEGACEP,interventional,"squamous cell carcinoma of the penis is a rare tumor in europe, whose prognosis and survival are influenced by metastatic lymph node involvement. its frequency in france is estimated at less than 1% of human cancers. this spread follows a sequential process via the superficial and deep inguinal lymph nodes and then to the pelvic lymph nodes before metastatic dissemination.

the management of inguinal areas is the cornerstone of penile cancer. it is curative in about 80% of patients with 1 or 2 inguinal metastases. 5-years overall survival was on average 85% for pn0 patients and 40% for pn+ patients. for pn+ patients, 5-year overall survival was 70 to 80% for pn1 (only 1 lymph node invasion), 30 to 40% for pn2, and 0 to 10% for pn3.

the risk of local recurrence is 5-10% for pn0 and 20-30% for pn+ after local treatment by lymphadenectomy alone without chemotherapy. the average time to recurrence was 10 months. disease-free survival at 5 years is 75-85% for pn0 and 30-45% for pn+. its indication depends on clinical examination (presence or absence of lymph nodes palpated) and the risk of nodal disease (≥pt1bg2).

currently, a fine needle biopsy is the best clinical diagnosis method because it is a simple, low risk, and possible in consultation. when the result is positive, it allows an early dissection. single or double fine needle biopsy will be used in cn+ patients. for patients at risk of lymp nodes involvement (cn0 and ≥pt1b or g2), the sentinel node diagnosis may be followed by modified or bilateral lymphadenectomy.

although lymphadenectomy alone has a curator action, it sometimes remains insufficient in patients with metastatic lymph node involvement. therefore it seems important to develop a multimodal approach in the management of these patients in order to increase the response rate to treatment and survival.

from a phase ii trial conducted on 30 patients, the combination tip (paclitaxel, ifosfamide, and cisplatin) appears to have an efficacy / toxicity acceptable.

the tip protocol has therefore been chosen for this trial as adjuvant or neo-adjuvant treatment in patients with high risk of lymph nodes involvement (cn0 and ≥pt1b or g2), and with inguinal mobile palpated lymph nodes (cn+) respectively, after lymph nodes involvement proven (pn+).","inclusion criteria:

penile tumor histologically proven whatever the initial treatment of penile tumor: amputation or conservative surgery or brachytherapy,
mobile palpated lymph nodes (stage cn1 and cn2) whatever the t stage, or if no palpated lymph nodes (cn0), patients with nodes involvement risk ≥pt1b and / or grade 2,
metastatic lymph node involvement,
patients m0 or mx,
age ≥18 ans,
eastern cooperative oncology group (ecog) 0-1,
leucocytes ≥1.5 g/l,
hemoglobin ≥9 g/dl,
platelets ≥100 000/mm³,
normal calcemia and kaliemia,
aspartate aminotransferase (ast) and alanine aminotransferase (alt) ≤1.5 upper limit of normal (uln) ; total bilirubin ≤1.5 uln (3 uln in case of gilbert disease); alkaline phosphatase (alp) <2 uln,
creatinine clearance ≥60 ml/min (mdrd method),
left ventricular ejection fraction (lvef) >50%,
patients having received, read the information note and signed consent,
reproductive age patients agreeing to use two methods of birth control (one for the patient and one for the partner) for the duration of the study and for 6 months after the last dose of treatment,
patients able to comply with the protocol requirements (scheduled visits, treatment plan, clinical, paraclinical, biological and other procedures of the protocol),
patients undergoing a social security scheme.

exclusion criteria:

fixed inguinal lymph nodes (cn3),
iliac lymph nodes (cn3),
patients pn3,
prior chemotherapy for squamous cell carcinoma of the penis,
against-indication for chemotherapy or known hypersensitivity to cisplatin, ifosfamide or paclitaxel,
patients treated with phenytoin,
patients with hearing loss >grade 1 (ctcae v4.03),
patients with cardiopulmonary disease-indicating against overhydration,
history of cancer within 5 years prior to inclusion in the trial other than cutaneous basal cell,
patient received a live attenuated vaccine within 30 days prior to inclusion,
patients already included in another clinical trial or receiving an experimental treatment within 30 days prior to inclusion in the trial,
patients deprived of their liberty or under court protection including guardianship,
severe systemic disease or uncontrolled or any other chronic or acute illness that is incompatible with the patient's participation in the trial according to investigator,
immunocompromised patients including with known seropositivity (hiv),
patients with mental impairment which prevents the understanding of the protocol or having a psychological state, family, sociological or geographical conditions that would not allow compliance with the protocol and the planned follow-up or any condition which, according to the investigator, would prevent participation patient tested. these conditions should be assessed before inclusion of patients.",1,0,1,0,0,0,18.0,200.0,Prostate,Prostate,1,0,Male
61,61,61,479,NCT02838381,2022-05-10,study of genetic and cellular immunological parameters predictive of disease-free survival in patients with metastatic cancer,study of genetic and cellular immunological parameters predictive of disease-free survival in patients with metastatic cancer,Epitopes-CRC01,interventional,the aim of this study is to characterize the genetic and cellular immunological parameters of metastatic digestive cancer patients having short and long responses to chemotherapy.,"inclusion criteria:

for all patients:

signed written informed consent

for cohort a:

patient with metastatic colorectal cancer with first-line therapy by chemotherapy +/- surgery and with a disease-free survival > or = at 20 months
ct-scan realized in the previous 4 weeks and showing no progression according to the recist criteria v1.1

for cohort b:

patient treated for metastatic colorectal cancer and chemotherapy responder (obtention of an objective response according to the recist criteria v1.1 in first-line therapy), with a disease-free survival < 10 months (disease progression must be confirmed by ct scan evaluation according to recist v1.1 criteria)

for cohort c:

patients with no metastatic rectum cancer in complete remission after chemotherapy and/or radiotherapy

for cohort d:

patients with metastatic or locally advanced cancer in complete remission after treatment, non eligible in the other cohorts

exclusion criteria:

for all patients:

patient with any medical or psychiatric condition or disease which would make the patient inappropriate for entry into this study
patient with a neurodegenerative disease
patient under guardianship, curator or under the protection of justice",1,0,0,0,0,1,18.0,200.0,Pleura,Pleura,0,0,All
62,62,62,480,NCT02838602,2021-09-01,randomized carbon ions vs standard radiotherapy for radioresistant tumors,transnational randomized study comparing carbon ions therapy versus conventional radiotherapy - including protontherapy - for the treatment of radioresistant tumors,ETOILE,interventional,"this is a transnational prospective randomized trial comparing definitive carbon ion therapy versus photon or combined photon and protontherapy as standard treatment for unresectable or macroscopically uncompleted resected radioresistant tumors. eligible tumors are axial chordoma (except of base of skull), adenoid cystic carcinoma of head and neck (except of trachea) and sarcomas of any site (except chondrosarcoma of the skull base), non previously irradiated and without pre-planned surgery or chemotherapy after the clinical trial procedure. randomization is balanced 1 for 1. patients of the experimental arm are treated in carbon ions centers in europe and patients of the standard arm are treated in france in their closest participating radiotherapy center. an accrual of 250 patients is needed and an absolute difference of 20% of relapse free survival at five years is awaited. the main endpoint is the progression free survival at five years. the trial is supported by the french program of clinical research and the national health insurance. two associated studies are carried out: a radiobiological one looking for radioresistance markers in the sarcomas biopsies, and the second one is about medico economics.","inclusion criteria:

age ≥ 18 years
no severe comorbidity, life expectancy above 10 years
unresectable or inoperable or r2 resection of the tumor

eligible radioresistant tumor according to the limitative list as following:

adenoid cystic carcinoma of head and neck (larynx and trachea excluded)
soft tissue sarcoma
pleomorphic rhabdomyosarcoma only (alveolar and embryonal forms excluded)
retroperitoneal sarcoma under condition of technical feasibility (movement)
osteosarcoma of any grade and localisation (ewing excluded)
chondrosarcoma (except of skull base) oms grade >= 2
chordoma axial skeleton or pelvis (except of skull base)
angiosarcoma
absence of epidermal invasion (a hypodermic invasion is accepted with fixity of cutaneous plan but not true epidermal permeation)
larger volume to be irradiated (ptv) less than 25 cm
ecog performance status ≤ 2 or karnovsky index ≥ 60
no pregnancy of possibility of pregnancy during the treatment
having an health insurance
signature of a written informed consent
validation of the randomization criteria: namely, a carbon ions therapy indication assessed by the medical team of a hadrontherapy center and able to by treated within two month from registration.

exclusion criteria:

complete macroscopic or microscopic surgical resection (r0 or r1)
previous irradiation in the volume to be treated
metastatic disease
disease not candidate to a curative approach (example accelerated progressive diseaseresistant to nay medical treatment especially for sarcoma)
any contra-indication to undergo a radiation therapy by xray or particle therapy
planned surgery or chemotherapy to take place after completion of radiotherapy (example : absence of enough space between an organ risk and the target volume (at least 5 mm) except the possibility of a spacer insertion)
planned surgery or chemotherapy after radiotherapy
presence in the target volume of metallic material which cannot be removed (carbon fibres matreial authorized)
history of concomittant (except in situ cervix carcinoma; or any cured basocellular cutaneous cancer tor any cured cancer with no sign of relapse during 5 years))
impossible follow-up over 5 years",1,0,0,0,0,1,18.0,200.0,Other,Other,0,0,All
63,63,63,481,NCT02839291,2022-05-10,"evaluation of medical practice in the management of bone metastases after injectable bone antiresorptive treatment, and its influence on quality of life","evaluation of medical practice in the management of bone metastases after injectable bone antiresorptive treatment, and its influence on quality of life",PRISM,interventional,"to evaluate the current medical practice and its influence on health-related quality of life, in patients who are treated with injectable bone antiresorptive drugs (biphosphonates or denosumab) for at least one year.","inclusion criteria:

patient with histologically proven tumor with bone metastasis, single or multiple (with or without metastasis extra-osseous)
patients treated with injectable bone antiresorptive therapy for 12 months or more
signed written informed consent

exclusion criteria:

patient with any medical or psychiatric condition or disease which would make the patient inappropriate to complete quality of life questionaries
patient under guardianship, curator or under the protection of justice, pregnant or breast-feeding women",1,0,0,0,0,1,18.0,200.0,Brain,Brain,0,1,All
64,64,64,484,NCT02841293,2021-03-02,cost-utility of two strategies of perineal reconstruction after abdominoperineal resection for anorectal carcinoma,cost-utility evaluation of two strategies of perineal reconstruction after abdominoperineal resection for anorectal carcinoma: perineal filling with biological meshes vs. primary perineal wound closure,GRECCAR-9,interventional,abdominoperineal resection performed for anorectal tumors leaves a large pelvic and perineal defect causing a high rate of morbidity of the perineal wound (40 - 60 %). biological meshes offer possibility for a new standard of perineal wound reconstruction. perineal filling with biological mesh is expected to increase quality of life by reducing perineal morbidity.,"inclusion criteria:

age ≥ 18
eastern cooperative oncology group performance status score of 2 or less
histologically proven rectal adenocarcinoma or anal canal epidermoïd carcinoma

abdominoperineal resection indication after multidisciplinary team discussion:

for rectal adenocarcinoma: circumferential mri margin equal or less than 1 mm from closest tumoral structure and a striated muscular layer (levator ani or external anal sphincter)
for epidermoid carcinoma: residual or recurrent tumour after chemoradiotherapy.
voluntary written informed consent
patients with social security insurance or equivalent social protection

exclusion criteria:

t4 tumour needing a surgical extensive resection with reconstruction by a musculocutaneous flap
metastasis disease deemed unresectable with curative intent
previous pelvic radiotherapy for another disease than the rectal or anal cancer
immunosuppressive drugs treatment
uncontrolled diabetes (glycosylated hemoglobin (hba1c) > 8 % despite adequate therapy)
patient under juridical protection.
sensitivity to porcine derived products.
enrolment in trial with overlapping primary endpoint.
pregnant women
breastfeeding women",1,0,0,0,0,1,18.0,200.0,Pleura,Pleura,0,1,All
65,65,65,487,NCT02843763,2022-08-01,study of specific cd4 tumors th1 responses in renal transplant after occurrence of cancer,study of specific cd4 tumors th1 responses in renal transplant after occurrence of cancer,TRAK,interventional,"as early complications of transplantation (acute rejection and infections) were better controlled and that the survival of kidney transplants has increased, chronic complications of immunosuppression became increasing challenges. the incidence of cancer is greatly increased in transplant and cancer is now the first cause of death. the iatrogenic immunosuppression plays a major role in the increased incidence of cancer. if it is accepted that the incidence of cancer is generally increased after transplantation, the increased risk is very different from a specific cancer to another. furthermore the specific treatment of the tumor (surgery, radiotherapy, chemotherapy, biotherapy), the specificity of the context of transplantation is related to the possibility of modulation of immunosuppression. however, there is no immunological marker for predicting the effectiveness of a modification of the immunosuppression.

several studies point to the important role of cd4 t cells into th1 anti-tumor immunosurveillance group cancers. identified ""helper"" degenerate peptides, called universal cancer peptide (ucp) derivative of telomerase, a type of tumor antigen universal. these ucp peptides bind most hla-dr alleles most frequent of the population and have the particularity of specifically stimulate cd4 t cells of type th1. using a test based on the ucp, it possible to detect the presence of spontaneous cd4 th1 anti-ucp answers in several types of human cancers.

the main objective of this study is to determine whether, in renal transplant patients, the occurrence of cancer is associated with a deficiency of cd4 th1 response anti-htert.","inclusion criteria:

men and women aged 18 to 80 years included
signature of informed consent for participation indicating that the subject has understood the purpose and procedures required by the study and agrees to participate in the study and comply with the requirements and limitations inherent in this study
join a french social security or receiving such a plan
group 1a: renal transplant patients reporting a first cancer (all types of cancer except skin inclued in group 2a or 2b)
group 1b: renal transplant patients without cancer (matched to patients in group 1a)
1c group: non transplant patients reporting a first cancer (patients matched to group 1a for the type and stage of cancer and the status cmv / ebv)
group 2a: kidney transplant patients reporting a single squamous cell carcinoma
group 2b: kidney transplant patients with multiple recurrences of squamous cell carcinomas.
group 2c: renal transplant patients without cancer (matched to patients in group 2a and 2b)

exclusion criteria:

legal incapacity or limited legal capacity
topic unlikely to cooperate in the study and / or low early cooperation by the investigator
without health insurance topic
pregnant woman
inability to understand the reasons for the study; psychiatric disorders judged by the investigator to be incompatible with the inclusion in the study
active infection or not by hiv",1,0,0,0,0,1,18.0,80.0,Kidney,Kidney,0,1,All
66,66,66,493,NCT02849535,2022-04-22,impact of the prism-care multidisciplinary oncology program on secured drug intake of patients with kidney cancer,"impact of the prism-care multidisciplinary oncology program versus usual care on secured drug intake of patients with kidney cancer, through self-management of adverse events related to oral targeted therapies, control of drug interactions, and sharing of the information between ambulatory and hospital settings.",PRISM care,interventional,"the rise of oral targeted therapies favors outpatient care of cancer patients but exposes them to new risks compared to the injectable chemotherapy in the hospital: non-adherence to treatment, inappropriate management of side effects and interactions with other co-prescribed drugs. the clinical consequences (reduced efficacy and potentialized toxicity) are all the more important that ambulatory monitoring of treatments prescribed at the hospital remains underdeveloped due to default of coordination between these two settings.

adverse drug reactions are a major concern, as such, and because they involve prescription changes (dose reduction, treatment interruption). this results in a decrease in the dose taken and a risk of loss of efficacy.

in the context of metastatic renal cell carcinoma, the risk of iatrogenicity is even higher because the oral targeted therapies available in this indication have a safety profile marked by potentially serious toxicities (hematologic and cardiac toxicity) or are known to reduce the treatment adherence (digestive and skin toxicities). in addition, these molecules are metabolized by the cyp3a4 hepatic cytochrome, which leads to avoid associating them with drugs inducing and / or inhibiting the cyp3a4, because of the risk of toxicity and / or loss of efficacy.

the investigators propose to assess a program set up to secure drug taking by enhancing self-management of side effects and control of drug interactions by the patient. this program includes pharmaceutical visits and involves inpatient and outpatient (doctor, referent pharmacist and liberal nurse) professionals.

the hypothesis of the study is that the prism care program will improve self-management of side effects by the patient, resulting in a relative dose intensity of oral chemotherapy improved compared to usual care.","inclusion criteria:

patient aged 18 years old or more
with metastatic renal cell carcinoma
with an initiation or change of oral targeted therapy, especially: tyrosine kinase inhibitor (sunitinib, sorafenib, pazopanib, axitinib) or mtor inhibitor (everolimus)
with ambulatory status (not hospitalized for the management and treatment of its metastatic renal cell carcinoma)
without either cognitive disorders or major psychiatric disorders
with a sufficient autonomy for the management of medication at home
having declared an outpatient doctor
having declared a usual pharmacy
having given his written consent to participate in the study

exclusion criteria:

significant cognitive and psychiatric disorders
management of medication at home exclusively performed by the family caregiver
patient in an institution or under guardianship, major protected by law
patient refusing to participate in the study",1,0,0,0,0,1,18.0,200.0,Kidney,Kidney,0,0,All
67,67,67,499,NCT02856425,2023-04-24,trial of pembrolizumab and nintedanib,phase ib trial of pembrolizumab and nintedanib,PEMBIB,interventional,"both anti-angiogenesis and anti pd1 immunotherapy have shown beneficial efficacy in solid tumors and in particular in nsclc. therefore it is of interest to investigate whether the combination of these two approaches is tolerable. moreover, comprehensive pre-clinical and clinical rationale sustain the hypothesis that anti-vegf could synergize with immunotherapy for the benefit of the patients.","inclusion criteria:

age ≥ 18

patients with advanced/metastatic cancer who have progressed after at least one line of standard therapy or are intolerant to standard therapy. patients must fit into one of the following groups:

colorectal adenocarcinoma (not mismatch repair deficient by either pcr and/or ihc) gastric or gastroesophageal adenocarcinoma (not mismatch repair deficient by either pcr and/or ihc patients with advanced or metastatic urothelial cancer (uc) patients with advanced renal cell cancer (rcc) patients with advanced mesothelioma (mpm) patients with advanced squamous cell carcinoma in cervical cancer (cc) patients with advanced hepatocellular (hcc) patients with advanced thymic carcinoma (tc) patients with advanced cancers and high tumor mutational burden (tmb-high) on their circulating tumor dna (ctdna) as defined by more than twenty mutations per megabase (≥20mut/mb) on foundationone liquid cdx assay. patients should be without known therapeutic options to provide clinical benefit.

ecog performance status of score 0 or 1

adequate organ function as defined by the following criteria :

proteinuria ≤ grade 2 nci ctcae v4.03
serum creatinine ≤1.5 x uln or calculated creatinine clearance ≥ 40 ml/min
total bilirubin within normal range (≤ 1.5 x uln if hcc)
ast and alt ≤ 1.5 x upper limit of normal (uln); if liver metastases ast and alt ≤ 2.5 x uln (≤ 5 x uln if hcc)
coagulation parameter : international normalized ratio (inr) < 2, prothrombin time (pt) and partial thromboplastin time (ptt) < 50% of deviation of uln
absolute neutrophils count (anc) ≥ 1000 cells/mm^3
platelets ≥100 000 cells/mm^3
hemoglobin ≥ 9.0 g/dl
at least one measurable lesion according to recist v1.1 (appendix 4) criteria and modified recist for mesothelioma only (appendix 6) or any other baseline prerequisite for the assessment of the principal judgment criteria.
women of childbearing potential (wocbp) must have a negative serum or urine pregnancy test within 7 days prior to initiation of treatment. both sexually active females and males (and their female partners) patients must agree to use two methods of effective contraception, one of them being a barrier method, or to abstain from sexual activity during the study and for at least 4 months after last study drug administration.
signed and dated written informed consent prior to admission to the study
patient affiliated to a social security regimen or beneficiary of the same

exclusion criteria:

prior treatment with nintedanib
known hypersensitivity to trial drugs or their excipients, peanut or soya or to contrast media
prior treatment with pembrolizumab or any other anti pd1 or anti-pdl1 agents
concurrent steroid medication (except topical or aerosol steroids). any steroid medication should have been stopped for more than 7 days prior beginning of therapy.
history of autoimmune/immune mediated inflammatory disease, including but not limited to colitis, pneumonitis, hepatitis, hypophysitis, nephritis, hyperthyroidism, systemic lupus erythematous, rheumatoid arthritis, inflammatory bowel disease, wegener's granulomatosis, sjögren's syndrome, guillain-barré syndrome, vasculitis, or glomerulonephritis (see appendix 3). patients with a history of auto-immune endocrinopathy (hypo/hyper thyroiditis, type 1 diabetes mellitus, …) and who are stable on hormone replacement therapy are eligible for the study. patients with a history of vitiligo, pelade, cutaneous psoriasis and grade 1-2 sjogren syndrome are eligible.
chemo-, hormono-, radio- (except for brain and extremities) or immunotherapy or therapy with monoclonal antibodies or small tyrosine kinase inhibitors within the past 4 weeks or 5 half-life times (whatever the shortest) prior to treatment with the trial drugs.
administration of a live, attenuated vaccine within 4 weeks before registration
treatment with systemic immunosuppressive medications (including but not limited to steroids azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-tnf] agents) within 2 weeks prior to registration
radiotherapy to the target lesion (unless a progression after radiotherapy has been documented)
persistence of clinically relevant treatment-related toxicity from previous chemotherapy, targeted therapy and/or radiotherapy
active brain metastases or leptomeningeal disease. clinically asymptomatic brain metastases and clinically asymptomatic leptomeningeal disease are allowed (treatment with steroids prior initiation of the trial is not allowed). patients with diffuse intrinsic pontine gliomas, even asymptomatic, are not allowed.
radiographic evidence of cavitary tumors with local invasion of major blood vessels and/or at risk for perforation
history of clinically significant hemoptysis within the past 3 months (more than one teaspoon of fresh blood per day)
treatment with other investigational drugs or treatment in another clinical trial within the past 4 weeks before start of therapy or concomitantly with the trial
therapeutic anticoagulation with drugs requiring inr monitoring (except low-dose heparin and/or heparin flush as needed for maintenance of an in-dwelling intravenous devise) or anti-platelet therapy (except for low-dose therapy with acetylsalicylic acid < 325mg per day)
major injuries and/or surgery within the past 4 weeks prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period
history of clinically significant hemorrhagic or thromboembolic event in the past 6 months
known inherited (genetic) predisposition to bleeding or thrombosis (such deficit in protein c/s) or acquired predisposition to thrombosis (such as anti-phospholipid syndromes)
history of significant cardiovascular diseases ( i.e. supraventricular tachycardia, uncontrolled hypertension, unstable angina, history of infarction within the past 12 months prior to start of study treatment, congestive heart failure > nyha ii, serious cardiac arrhythmia, pericardial effusion)
ongoing uncontrolled auto-immune thyroiditis. ancient thyroiditis currently stable with substitutive therapy should not be excluded from the trial.
other malignancies within the past 5 years other than basal cell skin cancer or carcinoma in situ of the cervix. a history of more than 3 years of local prostate cancer treated by surgery and without psa elevation since surgery, or local breast carcinoma treated by surgery without relapse are eligible.
active serious infections in particular if requiring systemic antibiotic or antimicrobial therapy
known to be human immunodeficiency virus (hiv) positive;
gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug
serious illness or concomitant non-oncological disease such as neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study.
pregnancy or breast feeding,
psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule
active alcohol or drug abuse
intake of ganoderma lucidum mushroom and/or herbal remedies and/or traditional medicines within the past 4 weeks prior to start of study treatment or concomitantly with the trial",1,1,0,0,0,0,18.0,200.0,Breast,Brain,0,0,All
68,68,68,504,NCT02861573,2023-10-06,study of pembrolizumab (mk-3475) combination therapies in metastatic castration-resistant prostate cancer (mk-3475-365/keynote-365),phase ib/ii trial of pembrolizumab (mk-3475) combination therapies in metastatic castration-resistant prostate cancer (mcrpc) (keynote-365),,interventional,"the purpose of this study is to assess the safety and efficacy of pembrolizumab (mk-3475) combination therapy in participants with metastatic castration resistant prostate cancer (mcrpc). there will be ten cohorts in this study: cohort a will receive pembrolizumab + olaparib, cohort b will receive pembrolizumab + docetaxel + prednisone, cohort c will receive pembrolizumab + enzalutamide, cohort d will receive pembrolizumab + abiraterone + prednisone cohort e will receive pembrolizumab+lenvatinib, cohort f will receive pembrolizumab+lenvatinib, cohort g will receive pembrolizumab/vibostolimab coformulation (mk-7684a), cohort h will receive pembrolizumab/vibostolimab coformulation, cohort i will receive pembrolizumab+carboplatin+etoposide in arm 1 and carboplatin+etoposide in arm 2 and cohort j will receive belzutifan in arm1 and pembrolizumab+belzutifan in arm 2. outcome measures will be assessed individually for each cohort.","inclusion criteria:

for cohorts a, b, c, d, e, g, j: has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology

for cohorts f, h, i: has t-ne or de novo metastatic prostate cancer defined by ≥1% neuroendocrine cells that are located in discrete regions of a recent biopsy specimen from a metastasis as determined by the investigational site and confirmed by central histology review prior to enrollment. epstein criteria of neuroendocrine differentiation in prostate cancer is used for eligibility. specimens must have one of the morphologies of small cell carcinoma or large cell neuroendocrine carcinoma (lcnec) or mixed (small or large cell) ne carcinoma - acinar adenocarcinoma with positive ihc confirmed by central pathology review
is able to provide tumor tissue from a site not previously irradiated as follows: cohorts a, e, g and j: must provide a core or excisional biopsy from soft tissue or bone biopsy within 1 year of screening and after developing mcrpc; cohort b: must provide an archival tumor tissue sample or tumor tissue from a newly obtained core or excisional biopsy from soft tissue if the lesion is clinically accessible; cohorts c and d with soft tissue disease: must provide a core or excisional biopsy from a soft tissue lesion if clinically accessible within 1 year of screening and after developing mcrpc and an archival specimen if available; and cohorts f, h, and i must provide a core or excisional biopsy from soft tissue or a bone biopsy. for de novo metastatic neuroendocrine prostate participants, biopsies must be performed within 1 year of screening. participants with bone metastasis only must provide an archival tumor tissue specimen
has prostate cancer progression within 6 months prior to screening, as determined by the investigator, by means of one of the following: psa progression as defined by a minimum of 2 rising psa levels with an interval of ≥1 week between each assessment where the psa value at screening should be ≥2 ng/ml; radiographic disease progression in soft tissue based on response evaluation criteria in solid tumors version 1.1 criteria with or without psa progression; radiographic disease progression in bone defined as the appearance of 2 or more new bone lesions on bone scan with or without psa progression. participants with de novo neuroendocrine prostate cancer will not need to provide evidence of progression within 6 months
has ongoing androgen deprivation with serum testosterone <50 ng/dl (<2.0 nm). treatment with luteinizing hormone-releasing hormone agonists or antagonists for all cohorts must have been initiated ≥4 weeks prior to first dose of study therapy and must be continued throughout the study. participants with de novo metastatic ne prostate cancer will not be required to have been previously treated with androgen deprivation therapy (adt). adt must be started in these participants by the time of treatment allocation/randomization
participants receiving bone resorptive therapy (including, but not limited to bisphosphonate or receptor activator of nuclear factor kappa-β ligand inhibitor) must be on stable doses for ≥4 weeks prior to first dose of study therapy
must be abstinent from heterosexual intercourse, refrain from donating sperm, or agree to use contraception (unless confirmed to be azoospermic) during the intervention period starting with the first dose of study therapy. the length of time required to continue contraception after the last dose of study intervention for each study intervention is as follows: 7 days for abiraterone acetate and lenvatinib; 30 days for enzalutamide; and 95 days for olaparib, docetaxel, and carboplatin/etoposide. no contraception measures are required during and after the intervention period for pembrolizumab/vibostolimab coformulation
has a performance status of 0, 1, or 2 on the eastern cooperative oncology group (ecog) performance scale for cohorts a and c and a performance status of 0 or 1 for cohorts b, d, e, f, g, h, i and j within 10 days of study start
for cohort a: has received docetaxel for mcrpc. prior treatment with 1 other chemotherapy for mcrpc is allowed. up to 2 second-generation hormonal manipulations (e.g., abiraterone acetate and/or enzalutamide) are allowed. prior docetaxel for metastatic hormone-sensitive prostate cancer is allowed if ≥4 weeks have elapsed from the last dose of docetaxel prior to day 1 of cycle 1
for cohort b: has received prior treatment with either abiraterone acetate or enzalutamide (but not both) in the prechemotherapy mcrpc state. participants in cohort b must have received at least 4 weeks of either abiraterone or enzalutamide treatment (but not both) who failed treatment or became intolerant of the drug
for cohort c: has received prior treatment with abiraterone acetate in the pre-chemotherapy mcrpc state without prior enzalutamide. participants in cohort c must have received at least 4 weeks of abiraterone treatment who failed treatment or become intolerant of the drug. participants who received abiraterone acetate in the hormone-sensitive state will not be eligible
for cohort d: has not received chemotherapy for mcrpc and has either not had prior second generation hormonal manipulation for mcrpc or has previously been treated with enzalutamide for mcrpc and failed treatment or has become intolerant of the drug. prior docetaxel for metastatic hormone-sensitive prostate cancer is allowed if ≥4 weeks have elapsed from the last dose of docetaxel. prior treatment with abiraterone acetate in the hormone-sensitive metastatic setting is allowed as long as there was no progression on this agent and abiraterone acetate was not discontinued due to adverse events (aes)
for cohorts e, g and j: has received docetaxel for mcrpc. prior treatment with 1 other chemotherapy for mcrpc is allowed. up to 2 second-generation hormonal manipulations (eg, abiraterone acetate, enzalutamide, apalutamide, darolutamide or other next-generation hormonal agents [nha]) are allowed. participants who received prior ketoconazole for metastatic disease may be enrolled. if docetaxel chemotherapy is used more than once (eg, once for metastatic hormone-sensitive and once for mcrpc), it will be considered as 1 therapy. prior docetaxel for metastatic hormone-sensitive prostate cancer (mhspc) is allowed if ≥4 weeks have elapsed from the last dose of docetaxel prior to day 1 of cycle 1
for cohort f, h, and i: participants must have received prior treatment with androgen deprivation therapy (adt) for metastatic disease. prior treatment with up to a total of 2 chemotherapies for mcrpc is allowed, as well as up to 2 second-generation hormonal manipulations for mcrpc. participants who received prior ketoconazole for metastatic disease may be enrolled. docetaxel for mhspc is allowed in addition to docetaxel for mcrpc. if docetaxel chemotherapy is used more than once (eg, once for metastatic hormone-sensitive and once for mcrpc), it will be considered as 1 therapy

exclusion criteria:

has had a prior anticancer monoclonal antibody (mab) within 4 weeks prior to first dose study therapy or who has not recovered (i.e., grade ≤1 or at baseline) from aes due to mabs administered >4 weeks earlier
has had prior chemotherapy, targeted small molecule therapy abiraterone treatment, enzalutamide treatment, or radiation therapy within 2 weeks prior to first dose of study therapy or who has not recovered (ie, grade ≤1 or at baseline) from aes due to a previously administered agent
is currently participating in and receiving study therapy or has participated in a study of an investigational agent and received study drug or used an investigational device within 4 weeks of treatment allocation/randomization
has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to treatment allocation/randomization
has had prior treatment with therapeutic radiopharmaceuticals for prostate cancer, such as radium-223 or leutitium-177, within 4 weeks prior to the first dose of trial treatment
has an active autoimmune disease that has required systemic treatment in past 2 years
has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease
has previously participated in any other pembrolizumab trial, or received prior therapy with an anti-programmed cell death 1 (anti-pd-1), anti-programmed cell death ligand 1 (anti-pd-l1), and anti-programmed cell death ligand 1 (anti-pd-l2)
has a known history of human immunodeficiency virus (hiv)
has known active hepatitis b or hepatitis c
has received a live vaccine or live-attenuated vaccine within 30 days of the first dose of study therapy
has known active central nervous system metastases and/or carcinomatous meningitis
has a ""superscan"" bone scan defined as an intense symmetric activity in the bones and diminished renal parenchymal activity on baseline bone scan such that the presence of additional metastases in the future could not be evaluated
has had prior solid, organ or bone marrow transplant
for cohort a: has experienced a seizure or seizures within 6 months of study start or is currently being treated with cytochrome p450 enzyme (cyp) inducing anti-epileptic drugs for seizures
for cohort a: is currently receiving strong or moderate inhibitors of cyp3a4 including azole antifungals; macrolide antibiotics; or protease inhibitors
for cohort a: is currently receiving strong or moderate inducers of cyp3a4
for cohort a: has myelodysplastic syndrome
for cohort a: has symptomatic congestive heart failure (new york heart association class iii or iv heart disease), unstable angina pectoris, cardiac arrhythmia, or uncontrolled hypertension
for cohort b: has received prior treatment with docetaxel or another chemotherapy agent for metastatic prostate cancer
for cohort b: has peripheral neuropathy common terminology criteria for adverse events ≥2 except due to trauma
for cohort b: has ascites and/or clinically significant pleural effusion
for cohort b:has symptomatic congestive heart failure (new york heart association class iii or iv heart disease)
for cohort b: is currently receiving any of the following classes of inhibitors of cyp3a4: azole antifungals; macrolide antibiotics; or protease inhibitors
for cohort c: has received prior chemotherapy for mcrpc. prior docetaxel for metastatic hormone-sensitive prostate cancer is allowed if ≥4 weeks elapsed from last dose of docetaxel. participants who received abiraterone acetate in the hormone-sensitive state will not be eligible
for cohort c: has a history of seizure or any condition that may predispose to seizure (including, but not limited to prior cerebrovascular accident, transient ischemic attack, or brain arteriovenous malformation; or intracranial masses such as a schwannoma or meningioma that is causing edema or mass effect)
for cohort c:has known or suspected brain metastasis or leptomeningeal carcinomatosis
for cohort c: has a history of loss of consciousness within 12 months of the screening visit
for cohort c: has hypotension (systolic blood pressure <86 millimeters of mercury [mmhg]) or uncontrolled hypertension (systolic blood pressure >170 mmhg or diastolic blood pressure >105 mmhg) at the screening visit
for cohort c: has received treatment with 5-α reductase inhibitors (e.g., finasteride, dutasteride), estrogens, and/or cyproterone within 4 weeks prior to cycle 1
for cohort c: has a history of prostate cancer progression on ketoconazole
for cohort d: has received prior treatment with docetaxel or another chemotherapy agent for metastatic prostate cancer
for cohort d: has progressed on prior abiraterone acetate for treatment of castration sensitive or resistant metastatic prostate cancer
for cohort d: has discontinued prior treatment with abiraterone acetate due to aes
for cohort d: has previously been treated with ketoconazole for prostate cancer for >7 days
for cohort d: has received prior systemic treatment with an azole drug (eg, fluconazole, itraconazole) within 4 weeks of cycle 1, day 1
for cohort d: has uncontrolled hypertension (systolic bp ≥ 160 mm hg or diastolic bp ≥ 95 mm hg)
for cohort d: has a history of pituitary or adrenal dysfunction
for cohort d: has clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or new york heart association class ii-iv heart disease or cardiac ejection fraction measurement of <50% at baseline
for cohort d: has atrial fibrillation, or other cardiac arrhythmia requiring therapy
for cohort d: has a history of chronic liver disease
for cohort d: is currently receiving strong cyp3a4 inducers (eg, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital) during abiraterone acetate treatment, cyp2d6 substrates with a narrow therapeutic index (for example thioridazine), or cyp2c8 substrates with a narrow therapeutic index (for example pioglitazone)
for cohorts e and f: has a left ventricular ejection fraction (lvef) below the institutional (or local laboratory) normal range, as determined by multigated acquisition (muga) or echocardiogram (echo)
for cohorts e and f: has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation
for cohorts e and f: has prolongation of qt interval by fredericia (qtcf) interval to >480 milliseconds
for cohorts e and f: has had major surgery within 3 weeks prior to first dose of study interventions
for cohorts e and f: has pre-existing ≥grade 3 gastrointestinal or non-gastrointestinal fistula
for cohorts e and f: has had significant cardiovascular impairment within 12 months of the first dose of study intervention, such as history of new york heart association >class ii congestive heart failure, unstable angina, myocardial infarction, or cerebrovascular accident (cva)/stroke, cardiac revascularization procedure, or cardiac arrhythmia associated with hemodynamic instability
for cohorts e and f: has active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of lenvatinib
for cohorts e and f: has gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib
for cohorts g, h, and i: has had a severe hypersensitivity reaction to treatment with another monoclonal antibody
for cohorts g, h, and i: has symptomatic ascites or pleural effusion
for cohort i: has clinically active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, and/or abdominal carcinomatosis
for cohort i: has received previous treatment for prostate cancer with platinum-containing compounds
for cohort j: has received docetaxel for mcrpc",1,1,1,0,0,0,18.0,200.0,Prostate,Prostate,0,0,Male
69,69,69,511,NCT02870907,2023-05-05,adjuvant treatment in extensive unilateral retinoblastoma primary enucleated (rb sfce 2009),adjuvant treatment in extensive unilateral retinoblastoma primary enucleated,,interventional,postoperative treatment of unilateral retinoblastoma after primary enucleation according to histopathological risk factors of the international retinoblastoma staging working group.,"inclusion criteria:

written informed consent - a signed informed consent and/or assent (as age appropriate) will be obtained according to institutional guidelines;
male or female ≥2 months and <10 years of age at the time of signing the informed consent form;
diagnosis of non familial extensive unilateral retinoblastoma treated by primary enucleation

in case of post operative chemotherapy, patients must have adequate organ function:

adequate hematopoietic function neutrophils>1.0x109/l, platelets >100 x 109/l.
adequate hepatic function: grade ii nci ctc
adequate renal function: serum creatinemia <1.5 x uln for age with normal creatinine clearance estimated by schwartz formula
audiometry < grade ii de brock.
echocardiography normal in case of high dose cyclophosphamide chemotherapy (3 g/m²).
patients affiliated to a social security regimen or beneficiary of the same
no chemotherapy or radiotherapy prior to administration of the first dose of study treatment for retinoblastoma or other tumor types
without medical cons-indication to study drugs.

exclusion criteria:

bilateral and/or familial or trilateral retinoblastoma.

unilateral retinoblastoma with indication of primary chemotherapy before enucleation:

one or several surgical risk factors
buphthalmia exophthalmia.
peri ocular inflammatory signs.
extraocular extension :
radiological retrolaminar extension (more than 3 mm behind the lamina cribrosa) and or meningeal sheat optic nerve extension.
extrascleral extension
lymp nodes extension
unilateral retinoblastoma with possibility of conservative treatment:
metastatic extension at diagnosis
one inclusion criteria non observed
uncontrolled medical conditions, psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol",1,0,1,0,0,0,0.1666666666666666,10.0,Pleura,Pleura,0,0,All
70,70,70,512,NCT02871167,2023-02-13,risk of infertility related to adjuvant chemotherapy for early breast cancer: oocyte/embryo cryopreservation,risk of infertility related to adjuvant chemotherapy for early breast cancer: oocyte/embryo cryopreservation (chacry-1501),CHACRY-1501,interventional,the aim of the study is to perform a french multicenter prospective interventional study in order to assess the feasibility and safety of ovarian hyperstimulation for oocyte / embryo cryopreservation in young women with breast cancer. the oncologic and reproductive benefit / risk ratio will be investigated in the oncology and reproductive area.,"inclusion criteria:

women with histologically proven breast cancer
aged 18 to 38 years old
planned adjuvant chemotherapy
no prior chemotherapy
affiliated to a public health insurance program
informed consent signed by the patient

exclusion criteria:

metastatic breast cancer
planned neo-adjuvant chemotherapy
hysterectomy
exclusive adjuvant hormonotherapy
positive serology for syphilis, hepatitis b or c, or vih
contraindication related to use of r-fsh
pregnant or breastfeeding patients",1,0,0,0,0,1,18.0,38.0,Breast,Breast,0,1,Female
71,71,71,514,NCT02874040,2020-03-27,endoresection of the tumor scar or transpupillary thermotherapy for the treatment of large uveal melanomas (endoresection-laser),phase ii evaluating endoresection of the tumor scar or transpupillary thermotherapy when endoresection is not feasible after proton beam therapy for the treatment of large uveal melanomas,,interventional,"study the efficacy of endoresection of the tumor scar or, when surgery is not possible, transpupillary thermotherapy on the tumor scar to prevent neovascular glaucoma and secondary enucleation","inclusion criteria:

tumor of 7 mm of thickness or more
patients treated by proton beam therapy
patients aged at least 18 years
patients clearly informed of the study, having received the letter of information and signed the consent

exclusion criteria:

massive extrascleral extension posterior to the equator
patients with metastasis at diagnosis.
patients with glaucoma before the radiation therapy
patients with opaque media preventing transpupillary thermotherapy
patients for whom follow up will be difficult due to geographical, social or psychological reasons",1,0,0,0,0,1,18.0,200.0,Other,Other,1,0,Female
72,72,72,517,NCT02875990,2016-08-17,characterization of immunosuppressive signing of cervical cancer,characterization of immunosuppressive signing of cervical cancer,Xac03,interventional,"infection with human papillomavirus high-risk human (hr-hpv) is the main factor of risk of cancer of the cervix. recent studies show that cancers linked to infection with hr-hpv are associated with immunosuppression and lack of t cell response such mechanisms would promote progression to cancer and progression of it . various factors such as an increase of regulatory t cells, the presence of myeloid cells and suppressor of defects in the signaling pathway toll like receptor (tlr) may have a key role in these immunosuppression mechanisms. at this stage of knowledge, a better characterization of local and systemic immunosuppressive signing of cervical cancer is needed. the results should have a significant medical impact for the identification of new prognostic markers and new therapeutic targets for the treatment of patients with cervical cancer.

the aim of this research project is to define the signing of immunosuppressive cancer cervix and analyze the different mechanisms involved in this immunosuppression.","inclusion criteria:

the women presenting for initial therapeutic management of cervical cancer
elderly patients over 18 years
patients beneficiary of a social security scheme
pregnant women can not participate in this study
women known to be hiv positive will not participate in this study

exclusion criteria:

patients with a recurrence of a treaty cervical cancer
patients with a history of pelvic radiotherapy
patients unable to receive informed about the progress and objectives of the study
patients not receiving a social security scheme
patients who have not signed informed consent
immunocompromised patients and pregnant women",0,0,0,0,0,1,18.0,200.0,Vulva,Vulva,0,1,Female
73,73,73,519,NCT02879864,2023-05-04,effect on fatigue of light (lux) therapy in patients with cancer,effect on fatigue of light (lux) therapy in patients with cancer,EFFLUX,interventional,"fatigue is a symptom most commonly associated with the diagnosis of cancer. fatigue often appears before the diagnosis of cancer, is increasing during treatment with chemotherapy and persists for years after treatment in more than 35% of patients. fatigue is the earliest and most important symptom described by cancer patients. its prevalence in cancer chemotherapy patients is between 70 and 100%. fatigue is more common to cancer patients and to the general population or other types of patients. typically described as a lack of energy associated with mental disorders, fatigue related to cancer can be extremely debilitating. the causes are many, mainly including the cancer itself, side effects due to treatment, sleeplessness due to pain, anxiety or depression. the cancer-related fatigue has a negative and significant direct impact on all aspects of the patient's quality of life, especially the physical, social and behavioral. despite the availability of certain treatments and the advanced biomedical research, fatigue remains an inevitable consequence of cancer and its treatment.

the therapeutic use of natural light in medicine dates back to the late nineteenth century. its remarkable effect on the stimulation of the immune system and fight against infections caused the development of the first therapy techniques (also called luxthérapie) awarded in 1903 by the nobel prize in medicine and physiology. light plays a fundamental role in the regulation of circadian rhythms and homeostatic. the mechanism of action passes through a path ""non-visual"" involving melanopsin ganglion cells located in the retina. activation of the pineal gland (epiphysis) by melanopsin cells allows transduce information ""shadow and light"" in melatonin synthesis from serotonin. today, the effectiveness of the therapy is well established for treating fatigue-related disorders such as chronic fatigue, seasonal depression or seasonal or non-certain sleep disorders and in which the melatonin metabolism is disturbed. light therapy, by its mechanism of action, allows reprogramming ""of the biological clock and improved synchronization of circadian rhythms.","inclusion criteria:

cancer histologically or cytologically confirmed (regardless of type)
patient eligible for first-line chemotherapy
life expectancy> 3 months
who ps ≤ 2
age ≥ 18 years
informed consent signed and dated
affiliation to a social security scheme

exclusion criteria:

macular degeneration
diabetic retinopathy
glaucoma
untreated cataract
patient treated with vitamin d
psychiatric disorders (bipolar disorder, paranoia, schizophrenia)
for patients with other comorbidities may indicate against-the practice of therapy: application specialist opinion (ophthalmologist or psychiatrist)",1,0,0,0,0,1,18.0,200.0,Pleura,Pleura,1,0,All
74,74,74,520,NCT02885753,2023-08-16,systemic oxaliplatin or intra-arterial chemotherapy combined with lv5fu2 +/- irinotecan and an target therapy in first line treatment of metastatic colorectal cancer restricted to the liver,systemic oxaliplatin or intra-arterial chemotherapy combined with lv5fu2 +/- irinotecan and an target therapy in first line treatment of metastatic colorectal cancer restricted to the liver,OSCAR,interventional,"colorectal cancer is the 3rd most common cancer in france and the 2nd cause of death from cancer. between 30 to 60% of patients develop limited or predominant liver metastases. surgical resection of these metastases, only curative treatment is not immediately possible in 10-15% of cases. in unresectable patients, current palliative treatments are based on systemic chemotherapy associated or not with the targeted therapies (anti-egfr (panitumumab), anti-vegf (bevacizumab)). in this patient population, special attention was paid to intensified treatment regimens in order to improve their efficiency and improving the tumoral response rate, the intensity of the response and its earliness correlate with improved overall and progression-free survival.

the intra-arterial use of oxaliplatin coupled with iv chemotherapy has yielded or levels of 64% in patients having survived one or more lines of chemotherapy iv and 62% in patients who have progressed on oxaliplatin iv. in addition, the hia administration of oxaliplatin limits systemic and especially neurological toxicities, thanks to a greater hepatic clearance.

in conclusion, the combination of systemic chemotherapy, targeted therapy and hiac with oxaliplatin has showed promising efficacy results associated with good tolerance from the first line onwards. indeed, we can expect from the phase ii recent data, a control rate close to 100%, with high response rates associated with early maturity and depth responses as well as prolonged survival. however, to date, in the absence of randomized trial testing this combination, this strategy does not have sufficient evidence to be integrated in our routine practices, and hiac remains limited to a few expert centers in treatment catch-up.","inclusion criteria:

histologically proven colorectal adenocarcinoma with hepatic metastasis(es)
at least one measurable hepatic metastasis according to the criteria recist v1.1
no other metastatic sites except lung nodules if number ≤ 3 and < 10 mm
ras mutation status known (determination of kras mutation (exons 2,3 and 4) and determination of the nras mutation (exons 2,3 and 4))
age ≥ 18
who ≤ 2 (appendix 4)
no prior treatment by chemotherapy except perioperative or adjuvant chemotherapy discontinued for more than 12 months
life expectancy > 3 months
pnn > 1500/mm3, platelets > 100 000/mm3, hb > 9 g/dlq
bilirubin < 25 mmol/l, ast < 5x uln, alt < 5 x uln, alp < 5 x uln, tp > 60%, proteinuria from 24h < 1 g
creatinine clearance > 50 ml/min according to mdrd formula (appendix 4)
patient affiliated to a social security scheme
patient information and signature of the informed consent

exclusion criteria:

contraindications specific to the installation of a kthia: thrombosis of the hepatic artery, arterial vascular anatomy may compromise a secondary hepatic resection.
patient immediately eligible for a curative therapy (surgical and/or percutaneous) after discussion in cpr
following alterations in the 6 months prior to inclusion: myocardial infarction, angina, severe/unstable angina, coronary artery bypass surgery, congestive heart failure nyha class ii, iii or iv, stroke or transient ischemic attack
hypertension not controlled by medical treatment (sbp > 140 mmhg and/or dbp> 90 mmhg with blood pressure taken according to the diagram of the has)
a history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess or active gastrointestinal bleeding in the 6 months preceding the start of treatment
progressive gastroduodenal ulcer, wound or fractured bone
abdominal or major extra-abdominal surgery (except diagnostic biopsy) or irradiation in the 4 weeks before starting the treatment
transplant patients, hiv positive or other immune deficiency syndromes
any progressive pathology not balanced over the past 6 months: hepatic failure, renal failure, respiratory failure
peripheral neuropathy > 1
patient with interstitial pneumonitis or pulmonary fibrosis
history of chronic diarrhea or inflammatory disease of the colon or rectum, or unresolved occlusion or sub-occlusion in symptomatic treatment
history of malignant pathologies during the past 5 years except basocellular skin carcinoma considered in complete remission or in situ cervical carcinoma, properly treated
patient already included in another clinical trial with an experimental molecule
any known specific contraindication or allergy or hypersensitivity to the drugs used in the study (cf rcp appendix 7)
known deficit in dpd
qt/qtc range > 450 msec for men and > 470 msec for women
k+ < lnl, mg2+ < lnl, ca2+ < lnl
lack of effective contraception in patients (men and/or women) of childbearing age, pregnant or breastfeeding women, women of childbearing age not having had a pregnancy test
persons deprived of liberty or under supervision
impossibility of undergoing medical monitoring during the trial for geographic, social or psychological reasons",1,0,0,1,0,0,18.0,200.0,Colon,Colon,1,0,All
75,75,75,523,NCT02890095,2023-02-20,persistent organic pollutants and breast cancers (popcase),"prospective, multicenter, epidemiological case-control study, to establish a possible correlation between persistent chemical contaminants (pops) and breast cancer.",POPCASE,interventional,"exposure to certain classes of chemical contaminants, including certain persistent organic pollutants (pops) with a character of endocrine disruptors, could be one of the factors that lead to increase incidence of breast cancer in the western world .

however, the causal role of pops in the onset of breast cancer remains nowadays unproven. preliminary epidemiological studies on the impact of these environmental factors in breast cancer etiology have ignored the critical periods of exposure. similarly, they have considered a limited number of pollutants (not including possible joint or synergistic effects between individual compounds) and did not distinguish the different breast cancer subtypes may have different etiologies or even of genetic susceptibility factors (pop polymorphism of detoxification enzymes).

thus, popcase study examines the association between the presence of breast cancer and the levels and exposure profiles to a group of pops measured in adipose tissue (at) and blood, in particular using spectrometric methods developed by the team laberca (nantes, france). these internal levels of pops (organochlorine pesticides, dioxins, pcbs, brominated flame retardants) will be measured both quantitatively (tissue concentrations) and qualitative (relative proportions of different pollutants sought).","inclusion criteria:

women ≥ 18 and <75 years

according to the arm:

arm a: histologically confirmed diagnosis of invasive breast cancer (only), unilateral or bilateral, outside off recurrence and relapse. patients who have been supported for a contralateral breast cancer can be included if a period of at least 2-years between the last systemic treatment of inclusion in the study.
arm b: any woman operated on for breast plastic surgery (breast lift and breast reduction cure only)
performance status (who) ≤ 1

5. patient affiliated to a social security scheme, 6. patient who signed and dated informed consent form 7. arm a only: unifocal lesion 8. arm a only: clinical stage m0

exclusion criteria:

patient with uncontrolled infection
patient pregnant or lactating
patient with a viral infection (hiv, hepatitis b, hepatitis c)
patient cannot be regularly monitored for psychological reasons, social, family or geographical.
patient private of liberty or under a guardianship authority / curatorship.
arm a only: patient to benefit from neoadjuvant therapy for breast cancer
arm a only patient with metastatic breast cancer
arm a only patient diagnosed cancer in situ (intra ductal)
arm a only patient with brca1 or brca2 known
arm b only: previous breast plastic surgery, regardless of the type of intervention",1,0,0,0,0,1,18.0,75.0,Breast,Breast,0,1,Female
76,76,76,533,NCT02912949,2022-12-23,a study of zenocutuzumab (mcla-128) in patients with solid tumors harboring an nrg1 fusion (enrgy),"a phase i/ii study of mcla-128, a full length igg1 bispecific antibody targeting her2 and her3, in patients with solid tumors (enrgy)",,interventional,"this is a phase i/ii, open-label, multi-center, multi-national, dose escalation, single agent study to assess the safety, tolerability, pk, pd, immunogenicity and anti-tumor activity of zenocutuzumab (mcla-128) in patients with solid tumors harboring an nrg1 fusion (enrgy)","inclusion criteria:

at least one measurable lesion according to recist v1.1 or evaluable disease for a limited number of patients (up to 10) in group h;
performance status of ecog 0 - 2;
estimated life expectancy of at least 12 weeks;
toxicities incurred as a result of previous anti-cancer therapy resolved to ≤grade 1;

treatment with anti-cancer medication or investigational drugs within the following intervals before the first dose of mcla-128:

>14 days or >5 half-lives prior to study entry, whichever is shorter.
>14 days for radiotherapy.
recovery from major surgery or other complication to ≤ grade 2 or baseline ;
absolute neutrophil count ≥1.5 x 109/l without colony stimulating factor support for at least 7 days prior to screening;
platelets ≥100 x 109/l without transfusion support for at least 7 days prior to screening;
hemoglobin ≥8 g/dl or ≥5 mmol/l;
alanine aminotransferase (alt), aspartate aminotransferase (ast) ≤3 x upper limit of normal (uln) and total bilirubin ≤1.5 x uln; in cases of metastatic liver involvement, alt/ast ≤5 x uln and total bilirubin ≤2 x uln will be allowed; in cases of antecedents of gilbert's syndrome when total bilirubin ≤3.0 x uln or direct bilirubin ≤1.5 x uln will be allowed;
estimated glomerular filtration rate (gfr) of >30 ml/min
able to provide a tumor biopsy sample (fresh strongly preferred or else archival);
not pregnant or nursing
fertile patients must use effective contraception during and for 6 month after completion of study therapy;
patients must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy or no satisfactory alternative treatment options are available;
locally-advanced unresectable or metastatic solid tumor malignancy with documented nrg1 gene fusion, identified through molecular assays such as next generation sequencing-based assays [dna or rna], as routinely performed at clia or other similarly-certified laboratories.

exclusion criteria:

pregnant or lactating;
presence of an active uncontrolled infection or an unexplained fever;
known hypersensitivity to any of the components of mcla-128;
known hiv, active hepatitis b without receiving antiviral treatment, or hepatitis c; patients treated for hepatitis c and have undetectable viral loads are eligible
known symptomatic or unstable brain metastases;
patients with leptomeningeal metastases
presence of congestive heart failure or left ventricular ejection fraction<50% or history of significant cardiac disease, unstable angina, myocardial infarction or ventricular arrhythmia requiring medication.
previous or concurrent malignancy (excluding non-basal cell carcinoma of skin or carcinoma in situ of the uterine cervix) unless the tumor was treated with curative intent more than 2 years prior to study entry;
presence of any other medical or psychological condition deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate or participate in the study, or interfere with the interpretation of the results.",1,0,1,0,0,0,18.0,200.0,Pleura,Pleura,0,1,All
77,77,77,537,NCT02924402,2023-02-27,study to evaluate safety and tolerability of xmab13676 (plamotamab) in patients with cd20-expressing hematologic malignancies,a phase 1 multidose study to evaluate the safety and tolerability of xmab13676 (plamotamab) in patients with cd20-expressing hematologic malignancies,,interventional,the purpose of this study is to determine the safety and tolerability of intravenous (iv) and subcutaneous (sc) administration of xmab13676 and to determine the maximally tolerated dose (mtd) and/or recommended dose (rd).,"inclusion criteria:

able to provide written informed consent
diagnosis of either non-cll b cell malignancy
ineligible for or have exhausted standard therapeutic options and have relapsed or refractory disease
ecog performance status 0-2
fertile patients must agree to use highly effective contraception during and for 5 months (male patients) and 8 months (female patients) after last dose of xmab13676
able and willing to complete the entire study

additional patient inclusion criteria for the dlbcl cohort (expansion phase)

histologically confirmed diagnosis (specified by 2016 world health organization) of dlbcl or transformed low-grade lymphoma with measurable disease
patient must be refractory or have relapsed after 2 or more standard therapeutic options, at least one of which must have included anti-cd20 antibody therapy.
not a candidate for or refusing treatment with hematopoietic stem cell transplantation

additional patient inclusion criteria for the follicular lymphoma cohort (expansion phase)

diagnosis of follicular lymphoma grades 1-3a
patient must be ineligible for or have exhausted standard therapeutic options and have had 2 or more prior systemic regimens.

exclusion criteria:

cytotoxic chemotherapy, radiotherapy, or immunotherapy including other anti-cd20 antibodies within 4 weeks, or small molecule or investigational agents within 5 elimination half-lives of the first dose of xmab13676
prior solid organ transplantation
failure to recover from grade 3 or 4 toxicity from previous treatment
multiple myeloma/plasma cell leukemia or b cell acute lymphoblastic leukemia
known intolerance to cd20 monoclonal antibody therapy
history of primary central nervous system lymphoma or neoplastic central nervous system disease
platelet count < 50 x 10^9/l
absolute neutrophil count < 1.0 x 10^9/l
aspartate aminotransferase (ast) and alanine aminotransferase (alt) at screening > 3x upper limit of normal (uln)
bilirubin > 1.5 mg/dl unless prior diagnosis and documentation of ongoing hemolysis or gilbert's syndrome has been made)
estimated creatinine clearance < 40 ml/min
active/uncontrolled autoimmune disease
clinically significant cardiac/cardiovascular disease, or pulmonary compromise
seizure disorder
history of stroke with the past 6 mos prior to study entry
history or evidence of a clinically unstable/uncontrollable disorder, condition or disease other than primary malignancy, that in the opinion of the investigator would pose a risk to the patient safety or interfere with the study evaluation, procedures or completion
evidence of any serious bacterial, viral, parasitic or systemic fungal infections within the 30 days prior to study entry
positive test for human immunodeficiency virus (hiv) or hepatitis c (hcv) antibodies (unless hcv viral load test by pcr is negative)
positive test for hbsag, or positive test for hbcab (unless serology is positive due to recent intravenous immunoglobulin therapy). hbcab positivity will be allowed if hbsab is present or hbv-dna is negative and patient is receiving hep b reactivation prophylaxis.
patient is pregnant or breast feeding, or planning to become pregnant while enrolled in the study, and 8 months after the last dose of study drug
positive urine pregnancy test (ie, urine human chorionic gonadotropin) at screening
live viral vaccine within 2 weeks of the first dose of xmab13676",1,1,0,0,0,0,18.0,200.0,Pleura,Pleura,1,0,All
78,78,78,542,NCT02934568,2023-10-10,ribociclib (lee011) rollover study for continued access,"an open-label, multi-center rollover protocol for patients who have participated in a novartis-sponsored ribociclib (lee011) study and are continuing to benefit from ribociclib as single agent or in combination with other investigational treatments",,interventional,this study is to allow continued use of ribociclib (lee011) as single agent or in combination with other investigational treatments in patients benefitting from treatment in an eligible novartis-sponsored ribociclib (lee011) study that has reached its primary objective(s) or has been halted for other reasons.,"inclusion criteria:

patient is currently enrolled in an eligible novartis-sponsored study and receiving ribociclib (lee011) as single agent or in combination with other investigational treatment.
patient is currently deriving clinical benefit from the study treatment, as determined by the investigator.

exclusion criteria:

patient has been permanently discontinued from ribociclib (lee011) in the parent protocol for any reason.
patients who do not meet parent protocol criteria to continue study treatment.",1,0,1,0,0,0,0.0,80.0,Colon,Pleura,0,0,All
79,79,79,546,NCT02938299,2023-10-06,neoadjuvant l19il2/l19tnf- pivotal study,"a pivotal phase iii, open-label, randomized, controlled multi-center study of the efficacy of l19il2/l19tnf neoadjuvant intratumoral treatment followed by surgery versus surgery alone in clinical stage iii b/c melanoma patients",Pivotal,interventional,"phase iii, open-label, randomized, controlled multi-center study of the efficacy of l19il2/l19tnf neoadjuvant intratumoral treatment in stage iii b/c melanoma patients.","inclusion criteria:

diagnosis of malignant melanoma of the skin with locally advanced disease as defined by clinical stage iii b and iii c according to ajcc 7th ed., eligible for complete surgical resection.
eligible subjects must have measurable disease and must be candidate for intralesional therapy with at least one injectable cutaneous, subcutaneous, or nodal melanoma lesion (≥ 10 mm in longest diameter) or with multiple injectable lesions that in aggregate have a longest diameter of ≥ 10 mm.
prior anti-tumor treatment for the primary melanoma lesion, including surgery and approved adjuvant treatments (e.g., radiotherapy, immune checkpoint inhibitors, braf/mek inhibitors, etc.) is allowed.
males or females, age ≥ 18 years.
ecog performance status/who performance status ≤ 1.
life expectancy of at least 24 months (see paragraph 6.3.1).
absolute neutrophil count > 1.5 x 109/l.
hemoglobin > 9.0 g/dl.
platelets > 100 x 109/l.
total bilirubin ≤ 30 µmol/l (or ≤ 2.0 mg/dl).
alt and ast ≤ 2.5 x the upper limit of normal (uln).
serum creatinine < 1.5 x uln.
ldh serum level ≤ 1.5 x uln.
documented negative test for hiv, hbv and hcv. for hbv serology, the determination of hbsag and anti-hbcag ab is required. in patients with serology documenting previous exposure to hbv (e.g., anti-hbsag and/or anti-hbc ab) negative serum hbv-dna is also required.
all acute toxic effects (excluding alopecia) of any prior therapy must have resolved to national cancer institute (nci) common terminology criteria for adverse events (ctcae) (v4.03) grade ≤ 1 unless otherwise specified above.
negative pregnancy test at screening for women of childbearing potential (wocbp*). pregnant women are not allowed to participate to this study. wocbp must be using, from the screening to three months following the last study drug administration, highly effective contraception methods, as defined by the ""recommendations for contraception and pregnancy testing in clinical trials"" issued by the head of medicine agencies' clinical trial facilitation group and which include, for instance, progesterone-only or combined (estrogen- and progesterone-containing) hormonal contraception associated with inhibition of ovulation, intrauterine devices, intrauterine hormone-releasing systems, bilateral tubal occlusion, vasectomized partner or sexual abstinence. pregnancy test will be repeated at the safety visit (only wocbp and only for patients in arm 1).
male patients with wocbp partners must agree to use simultaneously two acceptable methods of contraception (i.e., spermicidal gel plus condom) from the screening to three months following the last study drug administration.
evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.

willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.

women of childbearing potential are defined as females who have experienced menarche, are not postmenopausal (12 months with no menses without an alternative medical cause) and are not permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral oophorectomy or bilateral salpingectomy).

exclusion criteria:

uveal melanoma, mucosal melanoma or melanoma with unknown primary.
evidence of distant metastases at screening.
previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (ta, tis & t1), second primary melanoma in situ or any cancer curatively treated ≥ 5 years prior to study entry.
presence of active infections (e.g., requiring antimicrobial therapy) or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study.
history within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris.
inadequately controlled cardiac arrhythmias including atrial fibrillation.
heart insufficiency (> grade ii, new york heart association (nyha) criteria).
lvef ≤ 50% and/or abnormalities observed during baseline ecg and echocardiogram investigations that are considered as clinically significant by the investigator.
uncontrolled hypertension.
ischemic peripheral vascular disease (grade iib-iv).
severe diabetic retinopathy.
active autoimmune disease.
history of organ allograft or stem cell transplantation.
recovery from major trauma including surgery within 4 weeks prior to enrollment.
known history of allergy to il2, tnf, or other human proteins/peptides/antibodies or any other constituent of the product.
breast feeding female.
anti-tumor therapy (except allowed treatments listed at point 3 of inclusion criteria) within 4 weeks before enrollment.
previous in vivo exposure to monoclonal antibodies for biological therapy (except allowed treatments listed at point 3 of inclusion criteria) in the 6 weeks before enrollment.
planned administration of growth factors or immunomodulatory agents (except allowed treatments listed at point 3 of inclusion criteria) within 7 days before enrollment.
patient requiring or taking corticosteroids or other immunosuppressant drugs on a long-term basis. limited use of corticosteroids to treat or prevent acute hypersensitivity reactions is not considered an exclusion criterion.
any conditions that in the opinion of the investigator could hamper compliance with the study protocol.
previous enrolment and randomization in this same study.",1,0,0,1,0,0,18.0,200.0,Lung,Brain,0,0,All
80,80,80,549,NCT02945033,2019-10-23,study on aspirin versus placebo in resected colon cancer with pi3k mutation stage iii or ii high risk,"french prospective randomised double blind study, on aspirin versus placebo in resected colon cancer with pi3k mutation",ASPIK French,interventional,"four retrospective studies were recently published on efficacy of aspirin in patients with surgically resected colon cancer. two of these studies strongly suggested that aspirin used in low doses (100 mg/d) after surgical resection of colorectal cancer with pi3k mutation could act as a targeted therapy with a major protective effect on the risk of recurrence. the other two studies did not confirm the benefit of aspirin in this situation. these four retrospective studies provide an insufficient level of evidence to demonstrate the benefit of low-dose aspirin as adjuvant to surgery for colorectal cancer. therefore, it is necessary as recommended in the conclusion of these studies and meta-analyses to perform a randomised prospective study to validate these data.","inclusion criteria:

age ≥ 18 years
colonic adenocarcinoma stage iii

colonic adenocarcinoma stage ii high risk mss:

t4bn0 or t4an0 tumour penetrating the surface of the visceral peritoneum
or less than 12 nodes evaluated;
or with at least two of the following criteria:lymphatic involvement, perineural invasion, venous invasion
or diagnosis of bowel obstruction or perforation; or poor differentiated tumour.
pi3k mutation, exon 9 or 20 (tumour)
resection r0
who performance status 0-2
chest and abdominal ct scan ≤ 8 weeks
life expectancy ≥ 3 years
written consent signed

exclusion criteria:

anticoagulant and/or antiaggregating treatment including clopidogrel
regular aspirin use (> 3 doses per week during more than 3 months the last year)
contraindication to aspirin : allergy to aspirin, active or antecedent peptic ulcer
severe renal or hepatic insufficiency
pregnancy or nursing ongoing
rectal cancer
hereditary forms (i.e. lynch syndrome patients)
follow-up of the patient not feasible",1,0,0,1,0,0,18.0,200.0,Colon,Colon,0,1,All
81,81,81,553,NCT02952508,2023-08-18,study of iopofosine i 131 (clr 131) in select b-cell malignancies (clover-1) and pivotal expansion in waldenstrom macroglobulinemia,"an open-label, multicenter, phase 2 study of iopofosine i 131 (clr 131) in patients with relapsed or refractory (r/r) select b-cell malignancies (clover-1) and expansion cohort in patients with waldenstrom macroglobulinemia (clover-wam)",CLOVER-WaM,interventional,"part a of this study evaluates iopofosine i 131 (clr 131) in patients with select b-cell malignancies (multiple myeloma( mm), indolent chronic lymphocytic leukemia (cll)/small lymphocytic lymphoma (sll), lymphoplasmacytic lymphoma (lpl)/waldenstrom macroglobulinemia (wm), marginal zone lymphoma (mzl), mantle cell lymphoma (mcl), diffuse large b-cell lymphoma (dlbcl), and central nervous system lymphoma (cnsl) who have been previously treated with standard therapy for their underlying malignancy. part b (clover-wam) is a pivotal efficacy study evaluating iv administration of iopofosine i 131 in patients with wm that have received at least two prior lines of therapy.","[clover-1] inclusion criteria: all patients

histologically or cytologically confirmed mm; patients with primary or secondary cnsl may be enrolled.
ecog performance status of 0 to 2
18 years of age or older
life expectancy of at least 6 months
platelets ≥ 75,000/µl (if full-dose anticoagulation therapy is used, platelets ≥ 100,000/µl are required)
wbc count ≥ 3000/µl
absolute neutrophil count ≥ 1500/µl
hemoglobin ≥ 9 g/dl (last transfusion, if any, must be at least 1 week prior to study registration, and no transfusions are allowed between registration and dosing)
estimated glomerular filtration rate ≥ 30 ml/min/1.73 m2
aspartate aminotransferase (ast) and alanine aminotransferase (alt) ≤ 2.5 × upper limit of normal (uln)
bilirubin < 1.5 × uln
international normalized ratio (inr) < 2.5
if patient is on full-dose anticoagulation therapy, the anticoagulation therapy must be reversible and reversal of the anticoagulation therapy must not be life-threatening, as judged by the investigator
patients who have undergone stem cell transplant must be at least 100 days from transplant

patients with multiple myeloma

at least 5 prior regimens, which must include at least 1 approved proteasome inhibitor (bortezomib, carfilzomib, or ixazomib), at least 1 approved immunomodulatory agent (thalidomide, lenalidomide, or pomalidomide), and at least 1 approved monoclonal antibody (e.g., daratumumab or elotuzumab) with or without maintenance therapy, unless patients are intolerable to such agents or ineligible to receive such agents.
at least triple-class refractory (refractory to a proteasome inhibitor, immunomodulatory agent, and a monoclonal antibody)

progressive disease defined by any of the following:

25% increase in serum m-protein from the lowest response value during (or after) last therapy and/or absolute increase in serum m-protein of ≥ 0.5 g/dl
25% increase in urine m-protein from the lowest response value during (or after) last therapy and/or absolute increase in urine m-protein of ≥ 200 mg/24 h
25% increase in bone marrow plasma cell percentage from the lowest response value during (or after) last therapy. absolute bone marrow plasma cell percentage must be ≥ 10% unless prior cr when absolute bone marrow plasma cell percentage must be ≥ 5%.
25% increase in serum flc level from the lowest response value during (or after) last therapy; the absolute increase must be > 10 mg/dl
new onset hypercalcemia > 11.5 mg/dl
failure to obtain a partial response or better to current treatment, or cannot further improve their response to current treatment
appearance of new extramedullary disease

measurable disease defined by any of the following:

serum m-protein > 0.5 g/dl
urine m-protein > 200 mg/24 h
serum flc assay: involved flc level ≥ 10 mg/dl provided serum flc ratio is abnormal.

[closed] patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, lymphoplasmacytic lymphoma/waldenstom macroglobulinemia, or marginal zone lymphoma

prior treatment with at least 2 prior regimens, which may include chemotherapy, an approved anti-cd20 antibody with or without maintenance therapy, and an approved targeted agent, unless patients are ineligible to receive such agents
patients with helicobacter pylori+ mucosa-associated lymphoid tissue lymphoma must have received 1 prior antibiotic regimen for h pylori
at least 1 measurable nodal lesion with longest diameter > 15 mm or 1 measurable extranodal lesion (eg, hepatic nodule) with longest diameter > 10 mm. additional parameters (e.g., measurable igm for patients with lymphoplasmacytic lymphoma) may be allowed if they meet current nccn guidelines for symptomatic disease. patients with uptake by fdg-pet scan may be allowed with prior approval of sponsor.

[closed] patients with mantle cell lymphoma

prior treatment with at least 1 prior regimen
at least 1 measurable nodal lesion with longest diameter > 15 mm or 1 measurable extranodal lesion (eg, hepatic nodule) with longest diameter > 10 mm. patients with uptake by fdg-pet scan may be allowed with prior approval of sponsor.

[closed] patients with diffuse large b-cell lymphoma

relapsed or refractory to combination chemotherapy for dlbcl that contains rituximab and an anthracycline; or is intolerable to such agents. relapsed disease is defined as either recurrence of disease after a cr or pd after achieving a partial response (pr) or sd. refractory disease is defined as failure to achieve at least sd with any 1 line of therapy or with pd ≤ 3 months of the most recent chemotherapy regimen.
at least 1 measurable nodal lesion with longest diameter > 15 mm or 1 measurable extranodal lesion (eg, hepatic nodule) with longest diameter > 10 mm. patients with uptake by fdg-pet scan may be allowed with prior approval of sponsor.

patients with cns lymphoma

must have biopsy-proven disease and must have received at least one prior intervention for their disease.
must be at least two weeks from cns biopsy before administration of iopofosine i 131.
must have at least one lesion with enhancement on brain imaging.
stable (or decreasing) dose of corticosteroids or anti-convulsant medication for at least 7 days prior to dosing

[clover-1] exclusion criteria:

ongoing grade 2 or greater toxicities due to previous therapies. stable, tolerable grade 2 aes (eg, neuropathy) may be allowed.
prior external-beam rt resulting in greater than 20% of total bone marrow receiving greater than 20 gy.
prior total body or hemi-body irradiation. patients who have received prior low-dose total body or hemi-body irradiation may be allowed on a case-by-case basis after discussion with sponsor (considerations may include factors such as time since irradiation, total lifetime accumulated dose, etc.)
extradural tumor in contact with the spinal cord or tumor located where swelling in response to therapy may impinge upon the spinal cord
for patients with cll/sll, lpl, or mzl, transformation to a more aggressive form of nhl
ongoing chronic immunosuppressive therapy
clinically significant bleeding event within prior 6 months
ongoing anti-platelet therapy (except low-dose aspirin [eg, 81 mg daily] for cardioprotection)
anti-cancer therapy within two weeks of initial iopofosine i 131 infusion. low dose dexamethasone for symptom management is allowed
radiation therapy, chemotherapy, immunotherapy, or investigational therapy within 2 weeks of eligibility-defining bone marrow biopsy.
for patients with primary or secondary cnsl, active bleeding in the tumor bed and/or uncontrolled seizure activity

[clover-wam] inclusion criteria

histologically or cytologically confirmed wm. patients with a diagnosis of lpl may be enrolled with prior sponsor approval.
patient has an eastern cooperative oncology group (ecog) performance status (ps) of 0 to 2 (appendix c)
patient is 18 years of age or older
life expectancy of at least 6 months
received at least two prior lines of therapy for wm
measurable igm (above upper limit of normal) or at least one measurable nodal lesion with longest diameter > 15 mm or one measurable extranodal lesion (e.g., hepatic nodule) with longest diameter > 10 mm

[clover-wam] exclusion criteria

ongoing grade 2 or greater toxicities due to previous therapies, excluding alopecia.
prior external-beam rt resulting in greater than 20% of total bone marrow receiving greater than 20 gy.
prior total body or hemi-body irradiation. patients who have received prior low-dose total body or hemi-body irradiation may be allowed on a case-by-case basis after discussion with sponsor (considerations may include factors such as time since irradiation, total lifetime accumulated dose, etc.)
patients with second malignancies in addition to wm, if the second malignancy has required therapy in the last 2 years or is not in remission; exceptions to this criterion include successfully treated non-metastatic basal cell or squamous cell skin carcinoma, or prostate cancer that does not require therapy
anti-cancer therapy within two weeks of initial iopofosine i 131 infusion.
need for acute treatment of wm (e.g., those with hyperviscosity)",1,0,1,0,0,0,18.0,200.0,Pleura,Pleura,0,0,All
82,82,82,556,NCT02960022,2023-10-31,a study for subjects with prostate cancer who previously participated in an enzalutamide clinical study,a phase 2 open-label extension study for subjects with prostate cancer who previously participated in an enzalutamide clinical study,,interventional,"the purpose of this study is to collect long term safety data in subjects who are continuing to derive clinical benefit from treatment with enzalutamide from the subjects participation in an enzalutamide clinical study sponsored by astellas or medivation (i.e., parent study) which has completed, at a minimum, the primary analysis or the study specified evaluation period.","inclusion criteria:

subject must currently be receiving enzalutamide for prostate cancer in a study sponsored by astellas or medivation and, based on the investigator's assessment, benefit from continued treatment. subjects participating in investigator-initiated trials are not eligible.
subject is able to continue on the treatment regimen that the subject was receiving in the prior study. if in the investigator's assessment, a change is needed to the subject's regimen (e.g., dose change in androgen deprivation therapy (adt) or dropping of a combination therapy) approval from a medical monitor is required prior to enrollment.
subject is able to swallow enzalutamide capsules and comply with study requirements.
subject and female partner who is of childbearing potential must continue to use 2 forms of birth control, of which 1 must be highly effective and 1 must be a barrier method throughout the study and for 3 months after final enzalutamide administration.
subject agrees to avoid sperm donation during the study and for at least 3 months after final enzalutamide administration.
subject agrees not to participate in another interventional study while on treatment.

canada specific:

institutional review board (irb)/independent ethics committee (iec) approved written informed consent and privacy language as per national regulations (e.g., health insurance portability and accountability act authorization for the united states sites) must be obtained from the subject prior to any study-related procedures.
subject must currently be receiving enzalutamide for breast cancer in a study sponsored by astellas or medivation/pfizer and based on the investigator's assessment, benefit from continued treatment. subjects participating in investigator-initiated trials are not eligible.
subject is able to continue on the treatment regimen that they were receiving in the prior study. if in the investigator's assessment, a change is needed to the subject's regimen (e.g., dropping of a combination therapy) approval from a medical monitor is required prior to enrollment.
subject is able to swallow enzalutamide capsules and comply with study requirements.
subject is either:
of nonchildbearing potential:
postmenopausal (defined as no spontaneous menses for at least 12 months prior to day 1 with follicle stimulating hormone (fsh) > 40 iu/l at day 1 for women < 55 years of age),
documented surgically sterile or status post hysterectomy (at least 1 month prior to day 1),
or, if of childbearing potential,
must have a negative urine pregnancy test at day 1 before the first dose of study drug is administered,
must use 2 acceptable methods of birth control starting at day 1 and through 6 months after the final study drug administration,
must not donate ova starting at first administration of study intervention and throughout 6 months after final study intervention administration.

the 2 acceptable methods of birth control are as follows or per local guidelines where these require additional description of contraceptive methods:

a barrier method (e.g., condom by a male partner) is required; and
one of the following is required:
placement of an intrauterine device (iud) or intrauterine system (ius);
additional barrier method including occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository;
vasectomy or other surgical castration at least 6 months before day 1.
the subject must not be breastfeeding at day 1 or during the study period, and for 6 months after the final study drug administration.
subject agrees not to participate in another interventional study while on treatment.

exclusion criteria:

subject met any of the discontinuation criteria or whose cancer progressed on the current enzalutamide clinical study in which subject is enrolling from.

subject requires treatment with or plans to use either of the following:

new systemic therapy for subjects cancer (palliative radiation therapy is allowed). the treatment with agents administered during previous studies which was stopped and then restarted during this study does not represent new treatment.
investigational therapy other than enzalutamide.
subject is currently participating in an investigator-initiated interventional trial and receiving enzalutamide.
subject has any concurrent disease, infection, or comorbid condition that interferes with the ability of the subject to participate in the study, which places the subject at undue risk or complicates the interpretation of data.

canada specific:

subject will be excluded from participation if any of the following apply:

subject met any of the discontinuation criteria or whose cancer progressed on the current enzalutamide clinical study in which they are enrolling from.
subject requires treatment with or plans to use any of the following:
new systemic therapy for their cancer (palliative radiation therapy is allowed). the treatment with agents administered during previous studies which was stopped and then restarted during this study does not represent new treatment.
investigational therapy other than enzalutamide.
subject is currently participating in an investigator-initiated interventional trial and receiving enzalutamide.
subject has any concurrent disease, infection, or comorbid condition that interferes with the ability of the subject to participate in the study, which places the subject at undue risk or complicates the interpretation of data in the opinion of the investigator.",1,0,1,0,0,0,18.0,200.0,Prostate,Prostate,0,0,Male
83,83,83,557,NCT02963363,2022-06-10,adapted physical activity for breast cancer her2 positive patient,feasibility study of an adapted physical activity (apa) for breast cancer patients treated by neoadjuvant chemotherapy and targeted therapy against her2,APACAN2,interventional,the purpose of this study is to assess the feasibility of a home-based adapted physical activity during neoadjuvant chemotherapy for her2+ breast cancer.,"inclusion criteria:

women > 18 years old
patient with her2 (human epidermal growth factor receptor 2) positive breast cancer histologically proven, eligible for neoadjuvant chemotherapy and targeted therapy against her-2
affiliation to the french social security scheme
patient who signed the participation consent before entering the trial
medical fitness certificate for sport

exclusion criteria:

diagnosis of a second malignancy in the past 5 years, with the exception of a basal cell skin cancer
metastatic cancer
karnofsky index ≤ 90%
men
pregnant women
significant psychiatric or neurological abnormality
patient deprived of liberty by a court or administrative
contraindication for physical activity
patient unable to complete questionnaires (language barrier)
participation in a clinical trial with the same objective",1,0,0,0,0,1,18.0,200.0,Breast,Breast,0,1,Female
84,84,84,571,NCT02984410,2023-02-28,"study assessing the ""best of"" radiotherapy vs the ""best of"" surgery in patients with oropharyngeal carcinoma","phase iii study assessing the ""best of"" radiotherapy compared to the ""best of"" surgery (trans-oral surgery (tos)) in patients with t1-t2, n0-n1 oropharyngeal, supraglottic carcinoma and with t1, n0 hypopharyngeal carcinoma",Best Of,interventional,"oropharyngeal squamous cell carcinoma (opscc) arises in the soft palate, tonsils, base of tongue, pharyngeal wall, and the vallecula. most of the patients with early stage opscc are usually cured. treatment of early stage opscc can be successfully achieved with primary surgery including neck dissection, as indicated, or with definitive radiotherapy. the current standard treatment for opscc is therefore based on either surgery and/or radiotherapy, both associated with comparable, high tumor control rates but with different side effects profiles and technical constraints.

in order to decrease the potential morbidity of surgery, transoral approaches have been developed within the last decades, including transoral robotic surgery (tors), transoral laser microsurgery (tlm) or conventional transoral techniques. on the other hand, patients with head and neck cancer treated with imrt experienced significant improvements in cause specific survival (css) compared with patients treated with non-imrt techniques thus suggesting that imrt may be beneficial in terms of patient's outcomes and toxicity profile. it is as yet unclear however, which one of the new techniques is superior to the other in terms of function preservation. given that the functional outcome of most importance is swallowing function, the preservation of swallowing is thus of major importance.

the main objective of the study is to assess and compare the patient-reported swallowing function over the first year after randomization to either imrt or tos among patients with early stage opscc, sgscc, and hpscc.","main inclusion criteria:

opscc in one of the following sub-sites: base of tongue, lateral pharyngeal wall, tonsil, glosso-tonsillar sulcus, vallecula or sgscc in one or more of the following sub-sites: epiglottis, aryepiglottic fold, false cord or hpscc in one or more of the following subsites: lateral and medial wall of piriform sinus (sub-sites are defined as lateral (lateral pharyngeal wall, tonsil, glosso-tonsillar sulcus, lateral piriform sinus) vs. central lesions (base of tongue, vallecula, all supraglottic sites, medial wall of piriform sinus))
tnm stage i-iii (7th ajcc classification): t1 or t2, n0 or t1 or t2, n1 with one single neck node ≤ 3cm without radiographic signs of extracapsular extension (ece), m0;
tnm stage i for hpscc: t1, n0, m0. ;
within 2 weeks before randomization, assessment by a multi-disciplinary team (mdt) composed of at least a head and neck/ent surgeon, oncologist, radiologist, radiotherapist, and pathologist of the treatment naïve patient and suitable for either tos or imrt based on:
ct with contrast and/or mri done within 4 weeks prior to randomization note: repeat contrast enhanced ct and/or mri or us 1 week or less prior to randomization in case of suspicious nodes <1cm on initial scan if per local practice
pan-endoscopy with assessment of trans-oral exposure for resection.
peri-nodal infiltration either via ct-scan or mri.
age 18 and older; age 18 to 70 for sgscc
ecog performance status ≤ 2;
availability of biological material for hpv/p16 testing for opsccs
study information and informed consent discussed by the surgeon and radio-oncologist and signed by the patient.
within 2 weeks prior randomization:
baseline mdadi score available;
adequate bone marrow function as demonstrated by neutrophils count > 1,5 109 /l , platelets count > 75 109 /l, wbc≥ 3.0 109 /l;
prothrombin time (pt) with an international normalized ratio (inr) ≤ 1.2
partial thromboplastin time (ptt) ≤ 1.2 times uln
women of child bearing potential (wocbp) must have a negative serum or urine pregnancy test no more than 72 hours prior to randomization.
patients of childbearing / reproductive potential should agree to use adequate birth control measures for 3 months, especially if they will undergo any radiotherapy treatment at any time during the study. a highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly.

main exclusion criteria:

any previous anti-cancer therapy for hnscc (surgery, chemo-, or radiotherapy or molecular targeted therapy);
any active malignancy (other than non-melanoma skin cancer or localized cervical cancer or localized and presumed cured prostatic cancer) within the last 5 years with ongoing systemic treatment
cancer in contact with the internal and/or common carotid artery
extension of opscc across the midline of the base-of-tongue
arytenoid involvement in case of sgscc
infiltration of apex for piriform sinus in case of hpscc
cancer originating from the soft palate or posterior pharyngeal wall
requirement of a reconstruction with a free or regional flap (i.e. involvement of >50% of the soft palate)
pre-existing dysphagia not related to the oropharyngeal cancer or diagnostic biopsies
any psychological, cognitive, familial, sociological or geographical condition potentially hampering compliance with the study protocol, completion of patient reported measures and follow-up schedule; those conditions should be discussed with the patient before registration in the trial",1,0,0,0,0,1,18.0,200.0,Pleura,Other,0,0,All
85,85,85,583,NCT02998385,2023-09-21,chemo-radiotherapy versus radiotherapy in the treatment of salivary glands and nasal tumors (imrt or protontherapy),a phase iii randomized study of chemo-radiotherapy versus radiotherapy alone in the adjuvant treatment of salivary glands and nasal tumors (imrt or protontherapy),SANTAL,interventional,"a phase iii, multicenter, randomized, open-label, french study comparing:

arm a : radiotherapy alone (66 to 70 gy; 5 fractions/week; 1fraction/day; 2 gy/fraction) (imrt or protontherapy)
arm b: radiotherapy (66 to 70 gy; 5 fractions/week; 1fraction/day; 2 gy/fraction; imrt or protontherapy) + concomitant cisplatin 100 mg/m2 iv on day 1 - j22 - 43 (3 cycles)","inclusion criteria:

- resected tumors of the sinus or the salivary glands t3-4, n1-3 or t1-2 n0, with overgrown banks or positive margins (< 5 mm)

or

unresectable or not operable tumors of salivary glands or sinuses

carcinomas of the main salivary glands (parotid, submandibular or sublingual glands) and accessories or malignant sinus tumors with any histological type except melanoma, lymphoma, mesenchymal tumor (sarcoma type), squamous cell carcinoma and nasopharyngeal carcinoma type 1, 2, 3.
age ≥ 18 years
performance status 0 -2 (who criteria)
for patients ≥ 70 years, the score to the g8 questionnaire must be > 14 with no fall in the previous 12 months or with a geriatric assessment consistent with the administration of chemotherapy
estimated life expectancy greater than or equal to 6 months
neutrophils > 1.5 x 109/l, platelets > 100 x 109/l, hemoglobin ≥ 9.5 g/dl, bilirubin ≤ 3 x upper normal value (uln), ast/alt < 5 uln, pal < 3 uln
creatinin clearance ≥ 60 ml/min (cockroft formula)
adequate cardiac function according to the investigator, compatible with the administration of cisplatin 100 mg/m²
affiliation to a social insurance or beneficiary of such a regimen
patient having given his written consent signed before any study specific procedure.

exclusion criteria:

history of radiotherapy in the ent region and/or neoadjuvant chemotherapy for the pathology concerned
synchronous metastases
contraindications for administration of cisplatin or carboplatin
allergy to cisplatin and/or its excipients
vaccination against yellow fever, recent or planned
administration of phenytoin with prophylactic purpose
other cancer, except for cancer in situ of the cervix, skin carcinoma (except melanoma) or cancer controlled for more than 5 years
pregnant, breastfeeding or without birth control woman. woman having the ability to procreate should have (serum or urinary) negative pregnancy test within 14 days prior to study treatment decision-making. (men or women) patients should use a reliable contraceptive method throughout the treatment and at least 6 months after the end of chemotherapy.
persons deprived of liberty under supervision or under curatorship, or unable to adhere to medical follow-up of the study for geographical, social or psychological reasons.",1,0,0,1,0,0,18.0,200.0,Vulva,Pleura,0,1,All
86,86,86,588,NCT03006172,2023-10-18,"to evaluate the safety, tolerability, and pharmacokinetics of inavolisib single agent in participants with solid tumors and in combination with endocrine and targeted therapies in participants with breast cancer","a phase i, open-label, dose-escalation study evaluating the safety, tolerability, and pharmacokinetics of gdc-0077 as a single agent in patients with locally advanced or metastatic pik3ca-mutant solid tumors and in combination with endocrine and targeted therapies in patients with locally advanced or metastatic pik3ca-mutant breast cancer",,interventional,"this is an open-label, multicenter, phase i study designed to evaluate the safety, tolerability, and pharmacokinetics of inavolisib administered orally as a single agent in patients with locally advanced or metastatic pik3ca-mutant solid tumors, including breast cancer, and in combination with standard-of-care endocrine and/or targeted therapies for the treatment of locally advanced or metastatic pik3ca-mutant breast cancer. participants will be enrolled in two stages: a dose-escalation stage (stage i) and an expansion stage (stage ii). participants will be assigned to one of seven regimens: inavolisib as a single agent (arm a), inavolisib in combination with palbociclib and letrozole (arm b), inavolisib in combination with letrozole (arm c), inavolisib in combination with fulvestrant (arm d), inavolisib in combination with palbociclib and fulvestrant (arm e), inavolisib in combination with palbociclib, fulvestrant, and metformin (arm f), and inavolisib in combination with trastuzumab and pertuzumab (and letrozole or fulvestrant, if applicable (arm g)).","inclusion criteria:

evaluable or measurable disease per recist, version 1.1 (measurable disease only for arm d)
eastern cooperative oncology group (ecog) performance status of 0 or 1
life expectancy of greater than or equal to (>=) 12 weeks
adequate hematologic and organ function, including blood counts, liver and kidney function

stage i arm a (inavolisib):

- locally advanced, recurrent, or metastatic, pik3ca mutant, incurable solid tumor malignancy, including breast cancer

stages i and ii, arms b and c:

- postmenopausal female participants with locally advanced or metastatic pik3ca-mutant hr+/her2- breast cancer

stage ii, arms d, e, or f:

- female participants with locally advanced or metastatic pik3ca-mutant hr+/her2- breast cancer

stage ii arm d:

- prior treatment with cdk4/6 inhibitor

stage ii arm g:

female participants with locally advanced or metastatic pik3ca-mutant her2+ breast cancer
left ventricular ejection fraction 50% or greater

stages i and ii:

- all participants must provide tumor tissue from the primary or metastatic tumor site obtained from a prior or new biopsy or surgical procedure for detection of pik3ca mutation by central laboratory test.

exclusion criteria:

metaplastic breast cancer
history of leptomeningeal disease
type 1 or 2 diabetes requiring anti-hyperglycemic medication
inability or unwillingness to swallow pills
malabsorption syndrome or other condition that would interfere with enteral absorption
known and untreated, or active central nervous system metastases
uncontrolled pleural effusion or ascites
any active infection that could impact patient safety or serious infection requiring intravenous antibiotics
history of other malignancy within 5 years, except for treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or stage i uterine cancer
history of or active ventricular dysrhythmias or congestive heart failure requiring medication or symptomatic coronary heart disease
congenital long qt syndrome, prolonged qt interval, or family history of sudden unexplained death or long qt syndrome

stage ii arms b, c, d, and e only:

prior treatment with >1 chemotherapy regimen for metastatic disease
prior treatment with pi3k inhibitor
history of significant toxicity related to mtor inhibitor requiring treatment discontinuation

stage ii arms b and e only:

- prior cdk4/6 inhibitor treatment

stage ii arm g only:

current uncontrolled hypertension or unstable angina
history of congestive heart failure, serious cardiac arrhythmia, or recent myocardial infarction
prior ejection fraction decrease on trastuzumab
prior cumulative doxorubicin greater than 360 mg/m2
symptomatic active lung disease
history of significant toxicity related to trastuzumab and/or pertuzumab requiring discontinuation of treatment",1,1,0,0,0,0,18.0,200.0,Breast,Breast,0,1,All
87,87,87,591,NCT03007147,2023-09-15,imatinib mesylate and combination chemotherapy in treating patients with newly diagnosed philadelphia chromosome positive acute lymphoblastic leukemia,international phase 3 trial in philadelphia chromosome-positive acute lymphoblastic leukemia (ph+all) testing imatinib in combination with two different cytotoxic chemotherapy backbones,,interventional,"this randomized phase iii trial studies how well imatinib mesylate works in combination with two different chemotherapy regimens in treating patients with newly diagnosed philadelphia chromosome positive acute lymphoblastic leukemia (all). imatinib mesylate has been shown to improve outcomes in children and adolescents with philadelphia chromosome positive (ph+) all when given with strong chemotherapy, but the combination has many side effects. this trial is testing whether a different chemotherapy regimen may work as well as the stronger one but have fewer side effects when given with imatinib. the trial is also testing how well the combination of chemotherapy and imatinib works in another group of patients with a type of all that is similar to ph+ all. this type of all is called ""abl-class fusion positive all"", and because it is similar to ph+ all, is thought it will respond well to the combination of agents used to treat ph+ all.","inclusion criteria:

for patients enrolled on apec14b1 prior to enrollment on aall1631, the required diagnostic bone marrow sample has been fulfilled

for patients who have not previously enrolled on apec14b1 prior to enrollment on aall1631, a baseline diagnostic sample (or peripheral blood sample with blasts if marrow sample unavailable) must be available to develop an mrd probe
in addition, laboratory reports detailing evidence of bcr-abl1 fusion or abl-class fusion must be submitted for rapid central review within 72 hours of study enrollment
>= 1 year (365 days) and =< 21 years at all diagnosis
ph+ (bcr-abl1 fusion): newly diagnosed de novo all (b-all or t-all) or mixed phenotypic acute leukemia (mpal meeting 2016 world health organization [who] definition) with definitive evidence of bcr-abl1 fusion by karyotype, fluorescence in situ hybridization (fish) and/or molecular methodologies
abl-class fusion: newly diagnosed b-all with definitive evidence of abl-class fusions. abl-class fusions are defined as those involving the following genes: abl1, abl2, csf1r, pdgfrb, pdgfra. methods of detection include fluorescence in-situ hybridization (fish, e.g. using break-apart or colocalization signals probes), multiplex or singleplex reverse-transcription polymerase chain reaction (rt-pcr), whole transcriptome or panel-based ribonucleic acid (rna)-sequencing (e.g. trusight rna pan-cancer panel; illumina, san diego, ca, usa or similar)
ph+ patients must have previously started induction therapy, which includes vincristine, a corticosteroid, pegaspargase, with or without anthracycline, and/or other standard cytotoxic chemotherapy
ph+ patients have not received more than 14 days of multiagent induction therapy beginning with the first dose of vincristine
ph+ patients may have started imatinib prior to study entry but have not received more than 14 days of imatinib
abl-class fusion patients must have previously completed the 4 or 5 weeks of multiagent induction chemotherapy (induction ia phase)
abl-class fusion patients may have started imatinib during induction ia, at the same time of or after the first vincristine dose
patients must have a performance status corresponding to eastern cooperative oncology group (ecog) scores of 0, 1, or 2
direct bilirubin =< 2.0 mg/dl
shortening fraction of >= 27% by echocardiogram
ejection fraction of >= 50% by radionuclide angiogram or echocardiogram

corrected qt interval, qtc < 480 msec

note: repeat echocardiogram and electrocardiogram are not required if they were performed at or after initial all diagnosis, before study enrollment

creatinine clearance or radioisotope glomerular filtration rate (gfr) >= 70 ml/min/1.73 m^2 or serum creatinine within normal limits based on age/gender, as follows:

1 to < 2 years: maximum serum creatinine 0.6 mg/dl (both male and female)
2 to < 6 years: maximum serum creatinine 0.8 mg/dl (both male and female)
6 to < 10 years: maximum serum creatinine 1 mg/dl (both male and female)
10 to < 13 years: maximum serum creatinine 1.2 mg/dl (both male and female)
13 to < 16 years: maximum serum creatinine 1.5 mg/dl (male), 1.4 mg/dl (female)
>= 16 years: maximum serum creatinine 1.7 mg/dl (male), 1.4 mg/dl (female)

exclusion criteria:

known history of chronic myelogenous leukemia (cml)
all developing after a previous cancer treated with cytotoxic chemotherapy
active, uncontrolled infection, or active systemic illness that requires ongoing vasopressor support or mechanical ventilation
down syndrome

pregnancy and breast feeding

female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential
lactating females who plan to breastfeed their infants
sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of treatment according to protocol
patients with congenital long qt syndrome, history of ventricular arrhythmias or heart block
prior treatment with dasatinib, or any tki other than imatinib",1,0,0,1,0,0,1.0,21.0,Pleura,Pleura,0,0,All
88,88,88,598,NCT03017326,2022-09-05,paediatric hepatic international tumour trial,paediatric hepatic international tumour trial,PHITT,interventional,"the phitt trial is an over-arching study for patients with hepatoblastoma (hb) and hepatocellular carcinoma (hcc). this trial will use a risk-adapted approach to the treatment of children diagnosed with hb.

children with hcc will be included as a separate cohort.","inclusion criteria:

clinical diagnosis of hb* and histologically defined diagnosis of hb or hcc.

*histological confirmation of hb is required except in emergency situations where:

a) the patient meets all other eligibility criteria, but is too ill to undergo a biopsy safely, the patient may be enrolled without a biopsy.
b) there is anatomic or mechanical compromise of critical organ function by tumour (e.g., respiratory distress/failure, abdominal compartment syndrome, urinary obstruction, etc.)
c) uncorrectable coagulopathy
age ≤30 years
written informed consent for trial entry

exclusion criteria:

any previous chemotherapy or currently receiving anti-cancer agents
recurrent disease
previously received a solid organ transplant; other than orthotopic liver transplantation (olt).
uncontrolled infection
unable to follow or comply with the protocol for any reason
second malignancy
pregnant or breastfeeding women",1,0,0,1,0,0,0.0,30.0,Kidney,Kidney,0,1,All
89,89,89,599,NCT03017573,2023-05-19,"prospective biobanking study in ovarian, breast, head and neck and cervical cancer patients aiming at better understand the link between the molecular alterations of the tumor itself, its microenvironment and immune response (scandare)","prospective biobanking study in ovarian, breast, head and neck and cervical cancer patients aiming at better understand the link between the molecular alterations of the tumor itself, its microenvironment and immune response (scandare)",SCANDARE,interventional,"scandare is a prospective biobanking study on tumor (+/- nodes), plasma and blood samples at different time points in ovarian, triple negative breast, head and neck cancer and cervical cancer patients. this study will allowed to identify new molecular and/or immunological biomarkers associated with clinical and biological features of the tumors. all patients will receive standard treatment according to the stage of the diseases and usual procédures.","inclusion criteria:

tumor types :

newly diagnosed treatment-naïve ovarian cancer patients eligible for surgery or neoadjuvant chemotherapy
newly diagnosed treatment-naïve triple-negative breast cancer patients eligible for surgery or neoadjuvant chemotherapy
newly diagnosed treatment-naïve head and neck cancer patients eligible for surgery
newly diagnosed treatment-naïve cervical cancer patients (1) stage ia - iia1 with nodal metastasis, postoperative positive margin or parametrial-vaginal involvement, and (2) stage ≥iia2).
male or female patients ≥ 18 years of age
signed informed consent

exclusion criteria:

male or female patients ≤18 years old
patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
individually deprived of liberty or placed under the authority of a tutor
patients not affiliated to the social security system",1,0,0,0,0,1,18.0,200.0,Breast,Breast,1,0,All
90,90,90,600,NCT03020251,2023-02-17,effects of preoperative rehabilitation in patients resected for lung cancer,effects of preoperative rehabilitation in patients resected for lung cancer,Rexochir,interventional,"this randomized controlled trial will evaluate the effect of a preoperative rehabilitation program at home in patients resected for lung cancer, comparing a control group (c group) receiving only chest physiotherapy and a rehabilitation group (r group) receiving both a training program at home and chest physiotherapy","inclusion criteria:

patients diagnosed for lung cancer (or highly suspicious for cancer tumor) eligible for resection surgery (lobectomy or pneumonectomy)
age > 18 years
presence of chronic obstructive pulmonary disease (copd) stages 2-4 of gold (forced expiratory volume (fev )/ forced vital capacity (fvc) <70%, fev <80% of predicted) and exertional dyspnea stage mmrc (medical research council) > 1
patients must provide written consent
member of social security scheme

exclusion criteria:

patients refusing to participate
copd stage 1 gold (vems >= 80% of the theoretical value)
presenting an operating contraindication during the initial maximal exercise test
presenting cardiac or vascular contraindication to achieve the readaptation program
patient living alone at home
patient with ventilatory assistance at home (oxygen therapy or noninvasive ventilation (niv))
with exercise hypoventilation (paco2 >45 mmhg)
cognitive difficulty
unable major
pregnancy,
patients deprived of liberty by a court or administrative decision",1,0,0,0,0,1,18.0,200.0,Lung,Lung,0,1,All
91,91,91,602,NCT03025477,2021-02-10,two therapeutic strategies in first-line in patients with epithelial advanced ovarian cancer,"randomized study assessing two strategies of first line: a strategy with intraperitoneal chemotherapy and a strategy with total intravenous strategy, in patients with epithelial advanced ovarian cancer",CHIMOVIP,interventional,chimovip is a study to determine the best therapeutic strategy in patient with ovarian advanced cancer.,"inclusion criteria:

histologically confirmed advanced (figo stage iii or iv) invasive epithelial ovarian cancer, primary peritoneal cancer, or fallopian-tube cancer. pleural cytology has to be performed in patients with pleural effusion.
initial intervention : debulking surgery or diagnostic surgery in the 3 weeks before inclusion
age ≥18 and < 75 years old.
eastern cooperative oncology group (ecog) performance status ≤ 2 before surgery (ecog ≤ 1 and lee score < 6 in patients > 70 years old).
adequate blood count (test realized in the past 14 days before inclusion) : neutrophils > 1500/mm3, platelets > 150 000/mm3.
creatinine clearance mdrd ≥ 60 ml/min
registration in a national health care system (cmu included).
signed and dated informed consent.

exclusion criteria:

figo stage iv extra-abdominal disease, with the exception of lymph nodes and pleural invasion.
patient having received previous chemotherapy for ovarian cancer.
left ventricular ejection fraction < 50% before chemotherapy initiation
other invasive cancer in the past 5 years (baso- and spinocellular cutaneous carcinoma with complete resection are accepted)
concomitant administration of prophylactic phenytoin or live attenuated viral vaccines such as yellow fever vaccine,
patients with known hypersensitivity to any component of study drug
patients without motivation or capacity to respect study requirements and constraints
pregnancy or breast feeding women",1,0,1,0,0,0,18.0,75.0,Pleura,Pleura,0,1,Female
92,92,92,603,NCT03026998,2020-11-03,mri screening of second primary cancer occurring within radiation fields after treatment by external beam radiation therapy for hereditary retinoblastoma (depiscarrh),mri screening of second primary cancer occurring within radiation fields after treatment by external beam radiation therapy for hereditary retinoblastoma,DepiSCARRH,interventional,the purpose of this study is to assess the benefit of mr screening for asymptomatic head & neck (or cns) second primary cancers occurring in hereditary retinoblastoma patients previously treated by external beam radiation therapy (ebrt).,"inclusion criteria:

personal history of hereditary retinoblastoma (i.e., familial history of retinoblastoma, or bilateral retinoblastoma, or unilateral multifocal retinoblastoma, or identified germline rb1 mutation or 13q deletion)
external beam radiation therapy (ebrt) used for retinoblastoma treatment
age at inclusion greater or equal to 7 years old.
time period between the end of ebrt and inclusion date of 5 years or more
written informed consent signed by patient (or legal representative)

exclusion criteria:

personal history of non-familial unilateral unifocal retinoblastoma without rb1 germline mutation.
personal history of second primary neoplasm occurring within radiation fields
contraindication for mri (pacemaker, intraocular metallic foreign body, defibrillators or other implanted electronic devices, intracranial ferro-magnetic clips) or associated conditions preventing from mr examination (intraocular prostheses and implants are not a contraindication for mri; orthodontic metallic devices are not a contraindication but might decrease the image quality and should be removed, if possible)
patients unable to comply with follow-up study requirements, for any geographical, social or psychological reason",1,0,0,0,0,1,7.0,200.0,Pleura,Pleura,0,0,All
93,93,93,611,NCT03040973,2023-05-04,study to allow patients previously participating in a novartis sponsored trial to continue receiving capmatinib treatment as single agent or in combination with other treatments or the combination treatment alone,"an open-label, multi-center, global, rollover study for patients who have previously been treated with capmatinib (inc280) as monotherapy or in combination in a novartis sponsored trial.",,interventional,the purpose of this study is to assess long-term safety and provide continued study treatment access to eligible participants who are judged by the investigator to benefit from continued treatment with capmatinib monotherapy or in combination with other treatments or with the combination treatment alone in a novartis sponsored study,"inclusion criteria:

participant is currently receiving capmatinib treatment (within novartis-sponsored study which is eligible and approved to transition participants to rollover study) as single agent or in combination or is receiving a combination treatment alone. this includes all participants treated with capmatinib in combination with other treatment that permanently discontinued capmatinib for any reason but are still receiving the combination treatment as single agent. in order to receive the combination treatment as single agent in the rollover study, the treatment needs to be not accessible to the participant outside a clinical trial (e.g. commercially not available or reimbursed).
participant is currently deriving clinical benefit from study treatment as determined by the investigator
willingness and ability to comply with scheduled visits, treatment plans and any other study procedures
written informed consent obtained prior to enrolling in the rollover study and receiving study medication. if consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness.

exclusion criteria:

participant is currently not receiving any study treatment due to unresolved toxicities for which study treatment dosing has been interrupted or permanently discontinued in the parent protocol (participants meeting all other eligibility criteria may be enrolled once toxicities have resolved to allow study treatment dosing to resume)
pregnant or nursing (lactating) women
women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while taking study treatment and for at least 7 days or following combination treatment parent trial recommendation (whichever is longer) of study treatment after stopping medication. highly effective contraception methods include:
concurrent participation in another clinical study other than a parent clinical study
participants who received live vaccines (e.g., intranasal influenza, measles, mumps, rubella, oral polio, bcg, yellow fever, varicella, ty21a typhoid vaccines and covid-19 vaccines) within 30 days prior to the first dose of study treatment",1,0,1,0,0,0,0.0,200.0,Other,Brain,0,1,All
94,94,94,613,NCT03042169,2022-03-14,surgical resection plus chemotherapy versus chemotherapy alone in oligometastatic stage iv gastric cancer,"surgical resection plus chemotherapy versus chemotherapy alone in oligometastatic stage iv gastric cancer - a multicenter, prospective, open-labeled, two-armed, randomized, controlled phase iii trial",SURGIGAST,interventional,surgical resection of the primary tumour and treatment of the metastatic site in oligometastatic stage iv metastatic gastric adenocarcinoma enhances survival and improves quality of life with acceptable postoperative morbidity and mortality in a selected group of operable patients with only one metastatic site that does not progress under chemotherapy.,"inclusion criteria:

primary diagnosis of uicc stage iv gastric adenocarcinoma with histological proof of the primary tumour (with her2 status, pcc histology and mmr status available and src histology available on anatomo-pathology reports)
without any form of previous treatment (surgery and / or chemotherapy and / or radiotherapy) for this diagnosis other than local endoscopic treatment. note : 3. ppatients having received first line chemotherapy for at least 2 months and completing inclusion/exclusion criteria can be included in the study at v2
locally resectable primary tumour and oligometastatic lesion accessible to surgical resection or local ablation procedure

oligometastatic lesion : retro-peritoneal lymph node metastases (rplm) and/or another metastatic lesion on only one organ (solid organ, lymph node or limited localised peritoneal carcinomatosis with pci < 7) according to the following non-exhaustive list of definitions:

rplm: para-aortal, intra-aorto-caval, para-pancreatic or mesenteric lymph node(s). note: in duodenum invading gastric cancer, retro-pancreatic nodes are not regarded as metastatic sites

other acceptable limited metastatic lesions:

localized potentially operable peritoneal carcinomatosis: pci < 7 including uni or bilateral krukenberg tumors (ovarian metastases)
liver: maximum of 5 metastatic lesions that are potentially resectable
lung: unilateral involvement, potentially resectable
uni- or bilateral adrenal gland metastases
extra-abdominal lymph node metastases such as supraclavicular or cervical lymph node involvement
localized bone involvement (defined as being within one radiation field) notes: 1. patients with more than one metastatic site in only one organ are eligible. 2. in case of doubt for considering whether a metastatic site is limited or not, please submit the case with relevant anonymised information to the medical coordinator of the study for approval. 6. only one solid organ metastatic site (hepatic, lung, adrenal gland, bone, brain...). patients with more than one metastatic lesion in only one organ are eligible
ecog performance status 0 or 1
man or women aged ≥ 18 years and ≤ 80 years
for surgery and/or chemotherapy, adequate cardiac, respiratory, bone marrow, renal and liver functions according to usual practices standards
ability to understand and complete quality of life questionnaires (eortc qlq c30 and qlq sto 22)
negative pregnancy test (urine or serum) performed prior to start the study in for females of childbearing potential with reproductive potential
male and female patients of child-bearing reproductive potential must agree to us an effective method of contraception approved by the investigator during the study and for a minimum of 6 months after the end of study treatment
patient covered by a government health insurance
patient who provides a signed written inform consent

exclusion criteria:

other histological subtype than adenocarcinoma
ecog performance status ≥ 2 2,3 or 4
diffuse peritoneal carcinomatosis (pci ≥ 7) or significant ascites
metastatic disease involving more than one solid organ metastatic site
primary tumor irresectability and/or metastatic lesion not accessible for resection or local ablation procedure or need for multi-visceral resection with expected high complication rate
contraindication to chemotherapy or surgery according to the multidisciplinary team decision
second uncontrolled malignant tumour
proximal (junctionnal) tumour growth across the z-line requiring additional trans thoracic oesophageal resectionµ
emergency surgery due to bleeding or perforation
age > 80 years
weight loss ≥ 20% persisting despite appropriate nutritional assistance
severe comorbid conditions that may jeopardize short term outcomes (e.g. cardiac, respiratory, bone marrow, renal or liver insufficiency...)
dihydropyrimidine dehydrogenase deficiency (dpd)
women who are pregnant or breastfeeding
patients in emergency situations
patients kept in detention and/or under legal protection under psychiatric care and/or interned in a social or psychiatric institution
adult patient under legal protection or in the incapacity to express his/her consent
patient not covered by a health insurance system",1,0,0,1,0,0,18.0,80.0,Gastric,Gastric,0,1,All
95,95,95,623,NCT03068663,2023-02-17,microbiota and the lung cancer,"characterization of microbiota (intestinal, from lungs, and upper airways) in patients with non-small cell lung carcinoma: exploratory study",MICA,interventional,"the subject is to study the lung microbiota and the one of upper airways (uas) (much less studied than the intestinal microbiota) in 40 patients having lung cancer. 20 patients undergo only surgical treatment, while other half receives also chemotherapy. the idea is to explore changes in microbiota of the lung, upper uas and intestine, and potentially find associations between them. these results will serve us as a base for the future study, focused on manipulation of the microbiota by prebiotics, probiotics or symbiotics and its effect on anti-cancer treatment tolerance and effectiveness.","inclusion criteria:

non small cell lung carcinoma patient suitable for surgery, or chemotherapy followed by surgery
bmi <29.9 kg/m²
not taking antibiotics, corticosteroids and/or immunosuppressants at least during two months before inclusion
not taking prebiotics, probiotics or symbiotics at least during two months before inclusion
signing the written consent before enrollment in the study
affiliation to the national health insurance (or system alike) according to the law from 9th august 2004

exclusion criteria:

cognitive difficulties
refusal of participation or inability to give a clear consent
digestive or pulmonary infection of a long duration during the two months preceding the study (with antibiotic treatment)
inflammatory digestive pathology
concurrent treatment with experimental medication, participation in another clinical therapeutic study within 30 days
presence of colostomy, total or partial gastrectomy
previous esophageal surgery
previous orl (otho-rhino-laryngo) cancer treated by radiotherapy or surgery
patient enable to follow the requirements of the study
patient deprived of his rights by administrative or judicial decision",1,0,0,0,0,1,18.0,80.0,Lung,Lung,0,0,All
96,96,96,631,NCT03075696,2023-11-06,"a dose escalation study of glofitamab (ro7082859) as a single agent and in combination with obinutuzumab, administered after a fixed, single pre-treatment dose of obinutuzumab in participants with relapsed/refractory b-cell non-hodgkin's lymphoma","a multicenter, open-label, phase i/ii study to evaluate the safety, efficacy, tolerability and pharmacokinetics of escalating doses of glofitamab (ro7082859) as a single agent and in combination with obinutuzumab administered after a fixed, single dose pre-treatment of obinutuzumab (gazyva®/gazyvaro™) in patients with relapsed/refractory b-cell non-hodgkin's lymphoma",,interventional,"this is a phase i/ii, multicenter, open-label, dose-escalation study designed to evaluate the efficacy, safety, tolerability and pharmacokinetics (pk) of a novel t-cell bispecific (tcb), glofitamab, administered by intravenous (iv) infusion as a single agent and in combination with obinutuzumab, following pre-treatment with a one-time, fixed dose of obinutuzumab. this entry-to-human study is divided in 3 parts: dose escalation (parts i and ii) and dose expansion (part iii). single-participant dose-escalation cohorts will be used in part i, followed by conversion to multiple participant dose-escalation cohorts (part ii), in order to define a tentative maximum tolerated dose (mtd) or optimal biological dose (obd). the expansion cohorts (part iii) will be initiated when the tentative mtd/obd is defined, to further evaluate the safety, pk and therapeutic activity of glofitamab.","inclusion criteria:

depending upon study part, a history or status of: 1) a histologically-confirmed hematological malignancy that is expected to express cluster of differentiation (cd)20; 2) relapse after or failure to respond to at least one prior treatment regimen; and 3) no available treatment options that are expected to prolong survival (e.g., standard chemotherapy or autologous stem cell transplant [asct])
measurable disease, defined as at lease one bi-dimensionally measurable nodal lesion, defined as > 1.5 cm in its longest dimension, or at least one bi-dimensionally measureable extranodal lesion, defined as > 1.0 cm in its longest dimension
able to provide a fresh biopsy from a safely accessible site, per investigator determination, providing the patient has more than one measurable target lesion
eastern cooperative oncology group (ecog) performance status of 0 or 1
life expectancy of >/=12 weeks
aes from prior anti-cancer therapy must have resolved to grade less than or equal to (</=) 1
adequate liver, hematological and renal function
negative serologic or polymerase chain reaction (pcr) test results for acute or chronic hepatitis b virus (hbv) infection
negative test results for hepatitis c virus (hcv) and human immunodeficiency virus (hiv)
negative serum pregnancy test within 7 days prior to study treatment in women of childbearing potential. women who are not of childbearing potential who are considered to be post-menopausal (at least 12 months of non-therapy amenorrhea) or surgically sterile (absence of ovaries and/or uterus) are not required to have a pregnancy test

exclusion criteria:

inability to comply with protocol mandated hospitalizations and restrictions
participants with chronic lymphocytic leukemia (cll), burkitt lymphoma and lymphoplasmacytic lymphoma
participants with a known or suspected history of hemophagocytic lymphohistiocytosis (hlh)
participants with acute bacterial, viral, or fungal infection at baseline, confirmed by a positive blood culture within 72 hours prior to obinutuzumab infusion or by clinical judgment in the absence of a positive blood culture
participants with known active infection, or reactivation of a latent infection, whether bacterial, viral, fungal, mycobacterial, or other pathogens or any major episode of infection requiring hospitalization or treatment with iv antibiotics within 4 weeks of dosing
prior treatment with systemic immunotherapeutic agents, including, but not limited to, radio-immunoconjugates, antibody-drug conjugates, immune/cytokines and monoclonal antibodies (e.g., anti-cytotoxic t-lymphocyte-associated protein 4 [anti-ctla4], anti-programmed death 1 [anti-pd1] and anti-programmed death ligand 1 [anti-pdl1]) within 4 weeks or five half-lives of the drug, whichever is shorter, before obinutuzumab infusion on cycle 1 day -7
history of treatment-emergent immune-related aes associated with prior immunotherapeutic agents
documented refractoriness to an obinutuzumab-containing regimen
treatment with standard radiotherapy, any chemotherapeutic agent, or treatment with any other investigational anti-cancer agent, including chimeric antigen receptor therapy (car-t) within 4 weeks prior to obinutuzumab infusion
prior solid organ transplantation
prior allogeneic sct
autologous sct within 100 days prior to obinutuzumab infusion
participant with history of confirmed progressive multifocal leukoencephalopathy (pml)
current or past history of central nervous system (cns) lymphoma
current or past history of cns disease, such as stroke, epilepsy, cns vasculitis, or neurodegenerative disease. participants with a past history of stroke that have not experienced a stroke or transient ischemic attack in the past 2 years and have no residual neurologic deficits are allowed.
evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders and known autoimmune diseases
participants with another invasive malignancy in the last 2 years (with the exception of basal cell carcinoma and tumors deemed by the investigator to be of low likelihood for recurrence)
significant or extensive history of cardiovascular disease such as new york heart association class iii or iv or objective class c or d cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina
administration of a live, attenuated vaccine within 4 weeks before obinutuzumab infusion or anticipation that such a live attenuated vaccine will be required during the study
received systemic immunosuppressive medications (including but not limited to cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within two weeks prior to obinutuzumab infusion. treatment with corticosteroid </= 25 mg/day prednisone or equivalent is allowed. inhaled and topical steroids are permitted.
any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug
history of autoimmune disease, including but not limited to myocarditis, pneumonitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus, erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, wegener's granulomatosis, sjögren's syndrome, guillain-barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. participants with a remote history of, or well controlled autoimmune disease, may be eligible to enroll after consultation with the medical monitor
in part iii dlbcl dexamethasone cohort, patients with a history of hypersensitivity to dexamethasone or systemic corticosteroids will be excluded",1,1,1,0,0,0,18.0,200.0,Pleura,Pleura,0,0,All
97,97,97,642,NCT03093116,2023-11-08,"a study of repotrectinib (tpx-0005) in patients with advanced solid tumors harboring alk, ros1, or ntrk1-3 rearrangements","a phase 1/2, open-label, multi-center, first-in-human study of the safety, tolerability, pharmacokinetics, and anti-tumor activity of tpx-0005 in patients with advanced solid tumors harboring alk, ros1, or ntrk1-3 rearrangements (trident-1)",TRIDENT-1,interventional,"phase 1 dose escalation will determine the first cycle dose-limiting toxicities (dlts), the maximum tolerated dose (mtd), the biologically effective dose and recommended phase 2 dose (rp2d) of repotrectinib given to adult subjects with advanced solid malignancies harboring an alk, ros1, ntrk1, ntrk2, or ntrk3 gene rearrangement.

midazolam ddi substudy will examine effect of of repotrectinib on cyp3a induction.

phase 2 will determine the confirmed overall response rate (orr) as assessed by blinded independent central review (bicr) of repotrectinib in each subject population expansion cohort of advanced solid tumors that harbor a ros1, ntrk1, ntrk2, or ntrk3 gene rearrangement. the secondary objective will include the duration of response (dor), time to response (ttr), progression-free survival (pfs), overall survival (os) and clinical benefit rate (cbr) of repotrectinib in each expansion cohort of advanced solid tumors that harbor a ros1, ntrk1, ntrk2, or ntrk3 gene rearrangement.","phase 1

key inclusion criteria:

histologically or cytologically confirmed diagnosis of locally advanced, or metastatic solid tumor (including primary cns tumors) (stage iv, american joint committee on cancer v.7) that harbors an alk, ros1, ntrk1, ntrk2, or ntrk3 gene rearrangement by protocol specified tests.
ecog ps 0-1.
age ≥18 (or age ≥ 20 of age as required by local regulation).
capability to swallow capsules intact (without chewing, crushing, or opening).
at least 1 measurable target lesion according to recist version 1.1. cns-only measurable disease as defined by recist version 1.1 is allowed.
prior cytotoxic chemotherapy is allowed.
prior immunotherapy is allowed.
resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to national cancer institute common terminology criteria for adverse events (nci ctcae) version 4.03 grade less than or equal to 1.
patients with asymptomatic cns metastases (treated or untreated) and/or asymptomatic leptomeningeal carcinomatosis are eligible to enroll if they satisfy the protocol specified criteria.
baseline laboratory values fulfilling the following requirements:absolute neutrophils count (anc) ≥1500/mm3 (1.5 × 109/l); platelets (plts) ≥100,000/mm3 (100 × 109/l); hemoglobin ≥ 9.0 g/dl transfusions are allowed; serum creatinine or creatinine clearance within normal limits or > 40 ml/min; total serum bilirubin < 1.5 × uln; liver transaminases (asts/alts) < 2.5 × uln; < 5 × uln if liver metastases are present alkaline phosphatase (alp); < 2.5 × uln; < 5 × uln if liver and/or bone metastasis are present; serum calcium, magnesium, and potassium normal or ctcae grade ≤ 1 with or without supplementation
life expectancy ≥ 3 months.

phase 2 key inclusion criteria

histologically or cytologically confirmed diagnosis of locally advanced, or metastatic solid tumor (including primary cns tumors) that harbors a ros1, or ntrk1-3 gene fusion.

subject must have a documented ros1 or ntrk1-3 gene fusion determined by tissue-based local testing using either:

a next-generation sequencing (ngs) or quantitative polymerase chain reaction (qpcr) test will be accepted to determine molecular eligibility.

• adequate tumor tissue needs to be sent to the sponsor designated central diagnostic laboratory for retrospective confirmation by a central diagnostic laboratory test selected by the sponsor.

or

a fluorescence in situ hybridization (fish) test and prospective confirmation of fusion status by a central diagnostic laboratory test selected by the sponsor prior to enrollment will be accepted to determine molecular eligibility.

adequate tumor tissue must be sent to the sponsor designated central diagnostic laboratory for prospective confirmation by a central diagnostic laboratory test selected by the sponsor prior to enrollment.
eastern cooperative oncology group (ecog) performance status 0-1.
age ≥12 (or age ≥ 20 as required by local regulation).
willing and able to provide written institutional review board (irb)/institutional ethics committee-approved informed consent or an assent signed by a parent or legal guardian for subjects age 12 to 17.
at least 1 measurable target lesion according to recist (v1.1) prospectively confirmed by blinded independent central radiology review (bicr), selected by sponsor, prior to enrollment. subjects with cns-only measurable disease ≥10 mm as defined by recist (v1.1) are eligible.

subjects with advanced solid tumors harboring ros1, ntrk1, ntrk2, or ntrk3 rearrangement will be assigned into 6 distinct expansion (exp) cohorts provided all inclusion and exclusion criteria are met.

i. exp-1: ros1 tki-naïve ros1+ nsclc ii. exp-2: 1 prior ros1 tki and 1 platinum based chemo ros1+ nsclc iii. exp-3: 2 prior ros1 tkis ros1+ nsclc (no chemo or io) iv. exp-4: 1 prior ros1 tki ros1+ nsclc (no chemo or io) v. exp-5: trk tki-naïve ntrk+ solid tumors vi. exp-6: trk tki-pretreated ntrk+ solid tumors

subjects with asymptomatic cns metastases (treated or untreated) and/or asymptomatic leptomeningeal carcinomatosis are eligible to enroll if they satisfy the protocol specified criteria.
baseline laboratory values fulfilling the following requirements:absolute neutrophils count (anc) ≥1500/mm3 (1.5 × 109/l); platelets (plts) ≥100,000/mm3 (100 × 109/l); hemoglobin ≥ 9.0 g/dl transfusions are allowed; serum creatinine or creatinine clearance > 40 ml/min; total serum bilirubin < 1.5 × uln; liver transaminases (asts/alts) < 2.5 × uln; < 5 × uln if liver metastases are present alkaline phosphatase (alp); < 2.5 × uln; < 5 × uln if liver and/or bone metastasis are present; serum calcium, magnesium, and potassium normal or ctcae grade ≤ 1 with or without supplementation
life expectancy ≥ 3 months.

key exclusion criteria phase 1 and phase 2

concurrent participation in another therapeutic clinical trial.
symptomatic brain metastases or leptomeningeal involvement.
history of previous cancer, except for squamous cell or basal-cell carcinoma of the skin, or any in situ carcinoma that has been completely resected, requiring therapy within the previous 2 years.
major surgery within 4 weeks of start of repotrectinib treatment. radiation therapy (except palliative to relieve bone pain) within 2 weeks of study entry. palliative radiation (≤10 fractions) must have been completed at least 48 hours prior to study entry
clinically significant cardiovascular disease (either active or within 6 months prior to enrollment): myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (new york heart association classification class ≥ ii), cerebrovascular accident or transient ischemic attack, symptomatic bradycardia, requirement for anti-arrhythmic medication. ongoing cardiac dysrhythmias of nci ctcae grade ≥2

any of the following cardiac criteria:

mean resting corrected qt interval (ecg interval measured from the onset of the qrs complex to the end of the t wave) for heart rate (qtcf) > 470 msec obtained from 3 ecgs, using the screening clinic ecg machine-derived qtc value any clinically important abnormalities in rhythm, conduction or morphology of resting ecg (e.g., complete left bundle branch block, third degree heart block, second degree heart block, pr interval > 250 msec) any factors that increase the risk of qtc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long qt syndrome, family history of long qt syndrome, or any concomitant medication known to prolong the qt interval.

known active infections (bacterial, fungal, viral including hiv positivity).
gastrointestinal disease (e.g., crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
peripheral neuropathy of ctcae ≥grade 2.
history of extensive, disseminated, bilateral, or presence of ctcae grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, and pulmonary fibrosis. subjects with history of prior radiation pneumonitis are not excluded.",1,1,1,0,0,0,12.0,200.0,Pleura,Brain,0,0,All
98,98,98,643,NCT03096041,2023-05-12,phase 3 study randomized evaluating the efficacy of auriculotherapy in patients with musculoskeletal pain by aromatase inhibitors,"phase 3 study randomized against placebo, evaluating the efficacy of auriculotherapy in patients with musculoskeletal pain by aromatase inhibitors in adjuvant treatment of breast cancer (triple-a)",TRIPLE-A,interventional,"auriculotherapy is a complementary medicine, with few side effects, without contraindication, inexpensive and not very restrictive.its efficacy has been found in several tests especially for the treatment of intraoperative pain. it remains more controversial in other indications. evaluation of the value of auriculotherapy is often difficult because of the methodological limitations of the trials conducted. in the daily practice, the auriculotherapy is proposed to improve the articular pains of patients treated by aa. this phase iii study aims at validate this approach.","inclusion criteria:

patient over 18 years of age
patients with anti-aromatases in adjuvant treatment of breast cancer
menopausal women
treatment with aromatase inhibitors (anti-aromatase, aa) initiated for more than 3 months. in the case of a change in anti-aromatase, the last treatment must be started for more than 3 months.
musculoskeletal pain appearing or increased under aa:
overall pain score of qcd ≥3 (on a scale of 0 to 10)
pain on at least 2 sites
pain for at least 3 months
history of radiotherapy and / or adjuvant chemotherapy authorized
patients may have received tamoxifen
patient affiliated to a social security system
patient mastering the french language and able to complete the evaluation questionnaires
free and informed consent

exclusion criteria:

patients who have already undergone treatment in auriculotherapy for the same indication
patient benefiting at the same time from a pncavt (acupuncture or homeopathy) for musculoskeletal pain
wearing hearing aids hindering the placement of semi-permanent needles (asp)
wearing of a valve prosthesis
patient under guardianship or unable to give informed consent
patient unable to undergo medical follow-up for geographical, social or psychopathological reasons",1,0,0,0,0,1,18.0,200.0,Pleura,Breast,0,1,Female
99,99,99,649,NCT03108495,2023-09-12,"study of ln-145, autologous tumor infiltrating lymphocytes in the treatment of patients with cervical carcinoma","a phase 2, multicenter study to evaluate the efficacy and safety using autologous tumor infiltrating lymphocytes (ln-145) in patients with recurrent, metastatic or persistent cervical carcinoma",,interventional,"prospective, multicenter, single-arm, open label, interventional study evaluating adoptive cell therapy (act) with autologous tumor infiltrating lymphocytes (til) infusion (ln-145) followed by il-2 after a non-myeloablative (nma) lymphodepletion preparative regimen for the treatment of patients with recurrent, metastatic, or persistent cervical carcinoma","inclusion criteria:

to be eligible for the study, patients must meet all of the following criteria prior to participation:

must be ≥ 18 years of age at the time of consent. enrollment of patients > 70 years of age may be allowed after consultation with the medical monitor.
must have recurrent, metastatic, or persistent squamous cell carcinoma (scc), adenosquamous carcinoma (asc), or adenocarcinoma (ac) of the cervix that is not amenable to curative treatment with surgery and/or radiation therapy.
at least one resectable lesion (or aggregate of lesions resected) of a minimum 1.5 cm in diameter post-resection to generate til; surgical removal with minimal morbidity (defined as any procedure for which expected hospitalization is ≤ 3 days)
at least one measurable target lesion, as defined by recist v1.1.

cohort 1 and cohort 2: progression during or following at least one, but no more than three, prior systemic chemotherapeutic treatments for recurrent, metastatic, or persistent cervical carcinoma

a line of systemic therapy is defined as any chemotherapy or multiple-agent chemotherapy regimen that was administered for recurrent, metastatic, or persistent scc, asc, or ac of the cervix.
a bevacizumab and chemotherapy combination is encouraged as a prior line of treatment.
neither chemoradiation, nor chemotherapy in the neoadjuvant or adjuvant settings are considered as a prior line of systemic therapy.

cohort 2: must also have previously received treatment with a checkpoint inhibitor (ie, pd-1, pd-l1]) in the setting of recurrent, metastatic, or persistent disease either as monotherapy or in combination (eg, in combination with chemotherapy or another immune agent)

cohort 3 (united states only): must have not received any therapies other than prior chemoradiation or surgery for loco-regional disease

any prior therapy directed at the malignant tumor, including chemotherapy, biologic/targeted agents, and immunologic agents must be discontinued at least 28 days prior to tumor resection.
have an eastern cooperative oncology group (ecog) performance status of 0 or 1
must have adequate organ function.
patient has no evidence of any active viral, bacterial, or fungal infection requiring ongoing systemic treatment. patients must be seronegative for the human immunodeficiency virus (hiv). patients with acute or chronic hepatitis infections may be enrolled if the viral load by nucleic acid amplification test (naat) is undetectable with/without active treatment
patients of childbearing potential must be willing to take the appropriate precaution to avoid pregnancy for the duration of the study and practice an approved, highly effective method of birth control during treatment and for 12 months after receiving the last protocol-related therapy.
prior to study enrollment (tumor resection), patient must have documentation of radiological disease progression after the most recent therapy

exclusion criteria:

patients who meet any of the following criteria are not eligible for participation in this study:

patients who have received an organ allograft or prior cell transfer therapy except for prior ln-145 therapy in the setting of re-treatment only.
patients who require ongoing systemic steroid therapy (> 10 mg/day of prednisone or other steroid equivalent dose).
patients who currently have prior therapy-related toxicities grade > 1 according to national cancer institute (nci) common terminology criteria for adverse events (ctcae) v5.0; except for peripheral neuropathy, alopecia, or vitiligo prior to enrollment (tumor resection).

. patients who have a history of hypersensitivity to any component or excipient of ln-145 or other study drugs:

• nma-ld preparative regimen (cyclophosphamide, mesna, and fludarabine)

patients who have active systemic infections, coagulation disorders, or other active major medical illness(es) of the cardiovascular, respiratory, or immune system, including evidence in the medical history of urinary tract obstruction, a positive cardiac stress test, myocardial infarction, cardiac arrhythmia, obstructive or restrictive pulmonary disease, or other conditions that in the opinion of the investigator would increase the risk of participation.

patients with symptomatic and/or untreated brain metastases (of any size and any number)

• patients with definitively treated brain metastases may be considered for enrollment, and must be stable for ≥ 14 days prior to beginning the nma-ld preparative regimen

patients who have any form of primary immunodeficiency (such as severe combined immunodeficiency [scid] or acquired immunodeficiency syndrome [aids])
patients who have a diagnosis of end-stage renal disorder requiring hemodialysis
patients who have a left ventricular ejection fraction (lvef) < 45% or who are new york heart association (nyha) class 2 or higher.
patients who have a documented forced expiratory volume in 1 second (fev1) of ≤ 60%
patients who have had another primary malignancy within the previous 3 years (except for curatively treated localized malignancy that has not required treatment for > 1 year, and in the judgement of the investigator, does not pose a significant risk of recurrence including, but not limited to, non-melanoma skin cancer or bladder cancer)

patients who are of the following protected classes will be excluded, including:

pregnant, parturient, or breastfeeding women
persons who are hospitalized without consent or those deprived of liberty because of a judiciary or administrative decision
patients with a legal protection measure or a person who cannot express his/her consent
patients in emergency situations who cannot consent to the study
patients who have received a live or attenuated vaccine within 28 days prior to beginning the nma-ld preparative regimen
patients whose cancer requires immediate attention or who would otherwise suffer a disadvantage by participating in this study
cohort 1 and cohort 3: patients who have received prior treatment with immunotherapy (eg, pd-1, pd-l1, or anti-cytotoxic t lymphocyte-associated antigen-4 [ctla-4] antibodies)
patients who have grade ≥ 2 hemorrhage within 14 days prior to enrollment (tumor resection)
cohort 3: patients may not have active or prior documented autoimmune or inflammatory disorders (including pneumonitis, inflammatory bowel disease [eg, colitis or crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, sarcoidosis syndrome, or wegener syndrome [granulomatosis with polyangiitis, graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]).",1,0,1,0,0,0,18.0,200.0,Lung,Pleura,0,0,Female
100,100,100,656,NCT03117972,2022-11-17,chemotherapy intensification in patients with high lactate dehydrogenase values and soluble syndecan1 levels,chemotherapy intensification in patients with high lactate dehydrogenase values and soluble syndecan-1 levels,CLavSyn,interventional,"in first-line metastatic colorectal cancer (mcrc), baseline prognostic factors allowing death risk and strategy stratification are lacking. in this setting, a simple biological scoring system have recently been proposed, including ldh and cd138 binary status seric values, identifying one third of patients with worst prognostic.

intensified-chemotherapy strategies, combining 5-fluorouracile, oxaliplatin, irinotecan and bevacizumab, are beneficial for patients having a bad prognostic, defined by the brafv600e mutation, concerning 5-8% of first line mcrc.

for the 30% of patients with ldh-cd138 elevated score, the purpose of clavsyn phase ii study is to compare the pfs of one intensified arm (folfoxiri bevacizumab) to one standard chemotherapy arm, in order to better discriminate treatment strategies, at metastatic diagnosis.","inclusion criteria:

performance status ecog-who 0 or 1
histologically proved metastatic colorectal adenocarcinoma, with non-resectable metastases
adequate hematological, hepatic, and renal functions
signed written informed consent

exclusion criteria:

previous treatment (chemotherapy, targeted therapy, surgery) for metastatic disease
history of autoimmune disease
acute infectious disease
known hypersensitivity grade 3-4 or contraindication to any of the study drugs
patient with any medical or psychiatric condition or disease which would make the patient inappropriate for entry into this study.
bevacizumab contraindication
brain metastases
other malignancy within the last 2 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer.
pregnancy, breast-feeding or absence of adequate contraception for fertile patients
patient under guardianship, curator or under the protection of justice.",1,0,1,0,0,0,18.0,76.0,Pleura,Pleura,0,1,All
101,101,101,657,NCT03121456,2022-08-10,18f-fdg pet scan and mri diffusion.evaluation of the early therapeutic response of diffuse large b-cell lymphoma,18f-fdg pet scan and mri diffusion : correlation study of the evaluation of the early therapeutic response of diffuse large b-cell lymphoma,LYMPHODTECT,interventional,"open-label, multicenter, uncontrolled and non-randomized study comparing 18f-fdg pet-scan and diffusion mri in the assessment of the early therapeutic response of diffuse large b-cell lymphoma.","inclusion criteria:

patient with diffuse large b-cell lymphoma confirmed histologically
patient with a tumor mass defined as measurable according to the recist 1.1 criteria,
patient requiring a standard first-line chemotherapy treatment (rituximab -cyclophosphamide - hydroxyadriamycin - oncovin - prednisone = r-chop every 21 days),
patient older than 18 years,
performance status less than or equal to 2,
biological assessment meeting the following criteria: creatinine <150 μmol / l or creatinine clearance> 40 ml / min, total bilirubin <30 μmol / l, transaminases <2.5 x uln
patient of childbearing age must agree to use means of effective contraception during the treatment period,
patient having read the information note and having signed informed consent,
patient with health care insurance available.

exclusion criteria:

history of malignant hemopathy or solid tumor
history of previous chemotherapy
contraindication to one of the examinations studied (claustrophobia, pacemaker ...)
patient included in another clinical trial for which a period of exclusion is mentioned.
patient considered to be a vulnerable person; vulnerable persons are defined in article l1121-5 to - 8: pregnant women, women who are pregnant, women who are breastfeeding, persons deprived of their liberty by a judicial or administrative decision, persons who are hospitalized without consent under articles l. 3212-1 and l. 3213-1 which do not fall under the provisions of article l. 1121-8 and persons admitted to a health or social institution for purposes other than research persons who are the subject of a legal protection measure or are unable to give their consent.",1,0,0,0,0,1,19.0,200.0,Vulva,Vulva,0,1,All
102,102,102,671,NCT03143322,2023-03-22,standard treatment +/- sbrt in solid tumors patients with between 1 and 3 bone-only metastases,extracranial stereotactic body radiation therapy (sbrt) added to standard treatment versus standard treatment alone in solid tumors patients with between 1 and 3 bone-only metastases,STEREO-OS,interventional,"bone metastases occur frequently during the evolution of solid tumors, either isolated or associated with visceral metastases. the incidence varies between 20 and 85% depending on the primary cancer. breast, prostate, and lung cancers are responsible for 70% of bone metastases. cancer with bone metastases compared to other metastatic sites is considered as associated with a better prognosis, particularly for breast and prostate cancer. bone metastases may be present at diagnosis (synchronous metastasis) or appear at a later time (metachronous metastasis).

the concept of ""oligometastases"" was proposed in patients with about 3 up to 5 metastases (without restriction on the primary site) and associated with an intermediate prognosis. it was hypothesized that local treatment with curative intent, aiming at the few metastatic sites, would yield long-term survival probabilities, along with systemic therapies.

long-term survivors have been reported after curative-intent treatment of metastasis in sarcoma and colorectal cancers with liver or lung metastasis. we chose to focus on bone metastasis because of their high incidence, their impact on the patient's quality of life and autonomy, and their accessibility to potentially curative radiotherapy.

the systemic treatment of metastatic cancer includes hormonal therapy (breast and prostate cancer), biologically-targeted drugs and chemotherapy (all cancers).

stereotactic radiotherapy is a highly accurate technique was initially developed for performing the radiosurgery of brain tumors in patients for whom it was deemed be too difficult to proceed to classical excision surgery. in this process, a high total dose of radiation is delivered in a single fraction to a well-defined intra-cranial target. the concept of radiotherapy in stereotactic conditions was extended to one or several fractions delivered to small volumes primary tumors/ metastases in extra-cranial sites (stereotactic body radiotherapy [sbrt]). at present, high control rates have been achieved for lung metastases. similarly, very high local control rates have been reported in bone metastases after stereotactic radiotherapy.

in this protocol, our purpose is to demonstrate, via a randomized phase iii trial, that high doses of radiotherapy, delivered in stereotactic conditions to the bone metastases (between 1 and 3 metastases) in solid tumor patients is able to improve the survival without progression.","inclusion criteria:

patients older than 18 years and younger than 75 years
good general condition: who performance status ≤1
patients with histological proof of breast, non-small cell lung, or prostate cancer
absence of co-morbidity contra-indicating radio-chemotherapy or surgery
primary tumor accessible to curative-intent treatment (surgery, chemoradiation…) for patients with synchronous metastases
patients with between 1 and 3 synchronous or metachronous bone metastases as defined by naf-pet and spinal mri (if necessary)
bones metastases treatable by sbrt
primary cancer considered to be controlled or accessible to curative-intent treatment (surgery, chemoradiation…) in case of locoregional reccurence for metachronous bone oligo-metastatic disease
women of childbearing potential and male patients must agree to use adequate contraception for the duration of study participation and up to 3 months following completion of therapy
patients who have received the information sheet, dated and signed the informed consent form
affiliated to the social security system

exclusion criteria:

visceral metastases as defined by fdg-pet (or f-choline-pet for prostate cancer) and cerebral ct or mri performed within six weeks before sbrt
previous systemic therapy for metastasis for patients with metachronous metastasis. prostate and breast cancer patients remain eligible if hormonal treatment was initiated 6 months before enrollment
all bone metastasis requiring surgical treatment (spinal cord compression, fracture…)
more than 3 bone metastases as defined by naf-pet or conventional spect-ct scan and spinal mri (if spinal bone metastases on naf-pet)
previous cancer within the 5 years before inclusion (except basal cell carcinoma of the skin, in situ carcinoma of the uterine cervix)
previous radiotherapy on bone metastasis (e.g: antalgic radiotherapy)
patient enrolled in another therapeutic trial
pregnant women or breast feeding mothers,
hypersensitivity to the active substance (fdg and naf or f-choline for prostate cancer) or to any of the excipients
contraindication to mri (in case of spinal metastases)
patients deprived of liberty or placed under the authority of a tutor. patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial. patients unable to understand the purpose of the study (language, etc.).",1,0,0,0,0,1,18.0,75.0,Pleura,Brain,0,1,All
103,103,103,673,NCT03145181,2023-11-08,"dose escalation study of teclistamab, a humanized bcma*cd3 bispecific antibody, in participants with relapsed or refractory multiple myeloma","a phase 1, first-in-human, open-label, dose escalation study of teclistamab, a humanized bcma x cd3 bispecific antibody in subjects with relapsed or refractory multiple myeloma",MajesTEC-1,interventional,the purpose of this study is to identify the recommended phase 2 dose(s) (rp2ds) and schedule assessed to be safe for teclistamab and to characterize the safety and tolerability of teclistamab at the rp2ds.,"inclusion criteria:

documented diagnosis of multiple myeloma according to international myeloma working group (imwg) diagnostic criteria
measurable multiple myeloma that is relapsed or refractory to established therapies with known clinical benefit in relapsed/refractory multiple myeloma or be intolerant of those established multiple myeloma therapies, and a candidate for teclistamab treatment in the opinion of the treating physician. prior lines of therapy must include a proteasome inhibitor, an immunomodulatory drug and anti-cd38 monoclonal antibody in any order during the course of treatment. participants who could not tolerate a proteasome inhibitor or immunomodulatory drugs and an anti-cd38 monoclonal antibody are allowed
eastern cooperative oncology group (ecog) performance status score of 0 or 1
female participants of childbearing potential must use acceptable method of contraception
participants must sign an icf indicating that he or she understands the purpose of and procedures required for the study and is willing to participate in the study. consent is to be obtained prior to the initiation of any study-related tests or procedures that are not part of standard-of-care for the participant's disease

exclusion criteria:

prior treatment with any b cell maturation antigen (bcma) targeted therapy
prior antitumor therapy as follows, before the first dose of study drug: targeted therapy, epigenetic therapy, or treatment with an investigational drug or used an invasive investigational medical device within 21 days or at least 5 half-lives, whichever is less; monoclonal antibody treatment for multiple myeloma within 21 days; cytotoxic therapy within 21 days; proteasome inhibitor therapy within 14 days; immunomodulatory agent therapy within 7 days; gene modified adoptive cell therapy (example, chimeric antigen receptor modified t cells, natural killer [nk] cells) within 3 months; radiotherapy within 14 days or focal radiation within 7 days
toxicities from previous anticancer therapies that have not resolved to baseline levels or to grade 1 or less except for alopecia or peripheral neuropathy
received a cumulative dose of corticosteroids equivalent to >= 140 milligram (mg) of prednisone within the 14-day period before the first dose of study drug (does not include pretreatment medication)
known active central nervous system (cns) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma",1,1,0,0,0,0,18.0,200.0,Pleura,Brain,1,0,All
104,104,104,680,NCT03157128,2023-10-10,"a study of selpercatinib (loxo-292) in participants with advanced solid tumors, ret fusion-positive solid tumors, and medullary thyroid cancer (libretto-001)","a phase 1/2 study of oral selpercatinib (loxo-292) in patients with advanced solid tumors, including ret fusion-positive solid tumors, medullary thyroid cancer, and other tumors with ret activation (libretto-001)",LIBRETTO-001,interventional,"this is an open-label, first-in-human study designed to evaluate the safety, tolerability, pharmacokinetics (pk) and preliminary anti-tumor activity of selpercatinib (also known as loxo-292) administered orally to participants with advanced solid tumors, including rearranged during transfection (ret)-fusion-positive solid tumors, medullary thyroid cancer (mtc) and other tumors with ret activation.","key inclusion criteria:

for phase 1:

participants with a locally advanced or metastatic solid tumor that:
has progressed on or is intolerant to standard therapy, or
for which no standard therapy exists, or in the opinion of the investigator, are not candidates for or would be unlikely to tolerate or derive significant clinical benefit from standard therapy, or
decline standard therapy
prior multikinase inhibitors (mkis) with anti-ret activity are allowed
a ret gene alteration is not required initially. once adequate pk exposure is achieved, evidence of ret gene alteration in tumor and/or blood is required as identified through molecular assays, as performed for clinical evaluation
measurable or non-measurable disease as determined by recist 1.1 or rano as appropriate to tumor type
eastern cooperative oncology group (ecog) score of 0, 1, or 2 or lansky performance score (lps) greater than or equal to (≥) 40 percent (%) (age less than [<] 16 years) with no sudden deterioration 2 weeks prior to the first dose of study treatment
adequate hematologic, hepatic and renal function
life expectancy of at least 3 months

for phase 2: as for phase 1 with the following modifications:

for cohort 1: participants must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the investigator, would be unlikely to tolerate or derive clinical benefit from appropriate standard of care therapy

cohorts 1 and 2:

enrollment will be restricted to participants with evidence of a ret gene alteration in tumor
at least one measurable lesion as defined by recist 1.1 or rano, as appropriate to tumor type and not previously irradiated
cohorts 3 and 4: enrollment closed

cohort 5:

cohorts 1-4 without measurable disease
mct not meeting the requirements for cohorts 3 or 4
mtc syndrome spectrum cancers (e.g., mtc, pheochromocytoma), cancers with neuroendocrine features/differentiation, or poorly differentiated thyroid cancers with other ret alteration/activation may be allowed with prior sponsor approval
cfdna positive for a ret gene alteration not known to be present in a tumor sample
cohort 6: participants who otherwise are eligible for cohorts 1, 2 or 5 who discontinued another ret inhibitor may be eligible with prior sponsor approval
cohort 7: participants with a histologically confirmed stage ib-iiia nsclc and a ret fusion; determined to be medically operable and tumor deemed resectable by a thoracic surgical oncologist, without prior systemic treatment for nsclc

key exclusion criteria (phase 1 and phase 2):

phase 2 cohorts 1 and 2: an additional known oncogenic driver
cohorts 3 and 4: enrollment closed
cohorts 1, 2 and 5: prior treatment with a selective ret inhibitor notes: participants otherwise eligible for cohorts 1, 2, and 5 who discontinued another selective ret inhibitor may be eligible for phase 2 cohort 6 with prior sponsor approval
investigational agent or anticancer therapy (including chemotherapy, biologic therapy, immunotherapy, anticancer chinese medicine or other anticancer herbal remedy) within 5 half-lives or 2 weeks (whichever is shorter) prior to planned start of loxo-292 (selpercatinib). in addition, no concurrent investigational anti-cancer therapy is permitted note: potential exception for this exclusion criterion will require a valid scientific justification and approval from the sponsor
major surgery (excluding placement of vascular access) within 2 weeks prior to planned start of loxo-292 (selpercatinib)
radiotherapy with a limited field of radiation for palliation within 1 week of planned start of loxo-292 (selpercatinib), with the exception of participants receiving radiation to more than 30% of the bone marrow or with a wide field of radiation, which must be completed at least 4 weeks prior to the first dose of study treatment
any unresolved toxicities from prior therapy greater than common terminology criteria for adverse events (ctcae) grade 1 at the time of starting study treatment with the exception of alopecia and grade 2, prior platinum-therapy related neuropathy
symptomatic primary cns tumor, metastases, leptomeningeal carcinomatosis, or untreated spinal cord compression. participants are eligible if neurological symptoms and cns imaging are stable and steroid dose is stable for 14 days prior to the first dose of loxo-292 (selpercatinib) and no cns surgery or radiation has been performed for 28 days, 14 days if stereotactic radiosurgery (srs)

clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of loxo-292 (selpercatinib) or prolongation of the qt interval corrected (qtcf) greater than (>) 470 milliseconds (msec)

participants with implanted pacemakers may enter the study without meeting qtc criteria due to nonevaluable measurement if it is possible to monitor for qt changes.
participants with bundle branch block may be considered for study entry if qtc is appropriate by a formula other than fridericia's and if it is possible to monitor for qt changes.
required treatment with certain strong cytochrome p450 3a4 (cyp3a4) inhibitors or inducers and certain prohibited concomitant medications
phase 2 cohort 7 (neoadjuvant treatment): participant must not have received prior systemic therapy for nsclc.",1,1,1,0,0,0,12.0,200.0,Thyroid,Thyroid,0,0,All
105,105,105,683,NCT03165734,2023-10-05,"a phase 3 study of pacritinib in patients with primary myelofibrosis, post polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis","a randomized, controlled phase 3 study of pacritinib versus physician's choice in patients with primary myelofibrosis, post polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis with severe thrombocytopenia (platelet count <50,000/μl)(pacifica)",PACIFICA,interventional,"this study (study id pac203 north america; pac303 ex-north america) is evaluating 200 mg bid of pacritinib compared to physician's choice (p/c) therapy in patients with mf and severe thrombocytopenia (platelet count <50,000/μl). approximately 399 patients in total will be enrolled, randomized 2:1 to either pacritinib (approximately 266 patients) or to p/c therapy (approximately 133 patients)

condition or disease: primary myelofibrosis/post-polycythemia vera myelofibrosis/ post-essential thrombocythemia myelofibrosis

intervention/treatment: drug-pacritinib","diagnosis and inclusion criteria

pmf (including pre-fibrotic mf), ppv-mf, or pet-mf (tefferi and vandiman 2008)
average platelet count of <50,000/µl at screening (day -35 to day -3) based on two measurements taken on different days; both measurements must be <50,000/µl
dipss intermediate-1, intermediate-2, or high risk (passamonti et al 2010)
palpable splenomegaly ≥5 cm below the lower costal margin (lcm) in the midclavicular line as assessed by physical examination
tss of ≥10 on the mpn-saf tss 2.0 or a single symptom score of ≥5 or two symptoms of ≥3, including only the symptoms of left upper quadrant pain, bone pain, itching, or night sweats

if the patient has received prior jak2 inhibitor treatment, this treatment must meet at least one of the following criteria:

prior treatment with any jak2 inhibitor, irrespective of dose, with a duration of 90 days or less. the 90-day period starts on the date of first administration of jak2 inhibitor therapy and continues for 90 calendar days, regardless of whether therapy is administered continuously or intermittently during that interval.
prior treatment with ruxolitinib, at no more than 10 mg total daily dose on any day, with a duration of 270 days or less. the 270-day period starts on the date of first ruxolitinib administration and continues for 270 calendar days, regardless of whether therapy is administered continuously or intermittently during that interval.the patient may not have received >10 mg of ruxolitinib on any day during that interval
age ≥18 years
eastern cooperative oncology group performance status 0 to 2
peripheral blast count of <10% throughout the screening period and at baseline
absolute neutrophil count of ≥500/µl
left ventricular cardiac ejection fraction of ≥50% by echocardiogram or multigated acquisition (muga) scan
adequate liver and renal function, defined by liver transaminases (aspartate aminotransferase [ast]/serum glutamic-oxaloacetic transaminase [sgot] and alanine aminotransferase [alt]/serum glutamic pyruvic transaminase [sgpt]) ≤3 × the upper limit of normal (uln) (ast/alt ≤5 × uln if transaminase elevation is related to mf), total bilirubin ≤4 x uln (in cases where total bilirubin is elevated, direct bilirubin ≤4 × uln, is required) and creatinine ≤2.5 mg/dl
adequate coagulation defined by prothrombin time/international normalized ratio and partial thromboplastin time ≤1.5 × uln
if fertile, willing to use effective birth control methods during the study
willing to undergo and able to tolerate frequent mri or ct scan assessments during the study
able to understand and willing to complete symptom assessments using a patient-reported outcome instrument
provision of signed informed consent

exclusion criteria

life expectancy <6 months
completed allogeneic stem cell transplant (allo-sct) or are eligible for and willing to complete other approved available therapy including allo-sct
history of splenectomy or planning to undergo splenectomy
splenic irradiation within the last 6 months
previously treated with pacritinib
treatment with any mf-directed therapy within 14 days prior to treatment day 1
any prior treatment with more than one jak2 inhibitor
treatment with an experimental therapy within 28 days prior to treatment day 1
systemic treatment with a strong cyp3a4 inhibitor or a strong cytochrome p450 (cyp450) inducer within 14 days prior to treatment day 1. shorter washout periods may be permitted with approval of the medical monitor, provided that the washout period is at least five half-lives of the drug prior to treatment day 1
significant recent bleeding history defined as national cancer institute common terminology criteria for adverse events (ctcae) grade ≥2 within 3 months prior to treatment day 1, unless precipitated by an inciting event (e.g., surgery, trauma, or injury)
systemic treatment with medications that increase the risk of bleeding, including anticoagulants, antiplatelet agents (except for aspirin dosages of ≤100 mg per day), anti-vascular endothelial growth factor (anti-vascular endothelial growth factor [anti-vegf]) agents, and daily use of cyclooxygenase-1 (cox-1) inhibiting nonsteroidal anti- inflammatory drugs (nsaids) within 14 days prior to treatment day 1
systemic treatment with medications that can prolong the qt interval within 14 days prior to treatment day 1. shorter washout periods may be permitted with approval of the medical monitor, provided that the washout period is at least five half-lives of the drug prior to treatment day 1
any history of ctcae grade ≥2 non-dysrhythmia cardiac conditions within 6 months prior to treatment day 1. patients with asymptomatic grade 2 non- dysrhythmia cardiovascular conditions may be considered for inclusion, with the approval of the medical monitor, if stable and unlikely to affect patient safety.
any history of ctcae grade ≥2 cardiac dysrhythmias within 6 months prior to treatment day 1. patients with non-qtc ctcae grade 2 cardiac dysrhythmias may be considered for inclusion, with the approval of the medical monitor, if the dysrhythmias are stable, asymptomatic, and unlikely to affect patient safety.
qt corrected by the fridericia method (qtcf) prolongation >450 ms or other factors that increase the risk for qt interval prolongation (e.g., hypokalemia [defined as serum potassium <3.0 meq/l that is persistent and refractory to correction], or history of long qt interval syndrome
new york heart association class ii, iii, or iv congestive heart failure
any active gastrointestinal or metabolic condition that could interfere with absorption of oral medication
active or uncontrolled inflammatory or chronic functional bowel disorder such as crohn's disease, inflammatory bowel disease, chronic diarrhea, or chronic constipation
other malignancy within 3 years prior to treatment day 1. the following patients may be eligible despite having had a malignancy within the prior 3 years: patients with curatively treated squamous or basal cell carcinoma of the skin; patients with curatively treated non-invasive cancers; patients with organ-confined prostate cancer with prostate-specific antigen (psa) <20 ng/ml and national comprehensive cancer network risk of very low, low, or favorable intermediate; and patients with curatively treated non-metastatic prostate cancer with negative psa.
uncontrolled intercurrent illness, including, but not limited to, ongoing active infection, psychiatric illness, or social situation that, in the judgment of the treating physician, would limit compliance with study requirements
known seropositivity for human immunodeficiency virus
known active hepatitis a, b, or c virus infection
women who are pregnant or lactating
concurrent enrollment in another interventional trial
severe thrombocytopenia due to vitamin b12 deficiency, folate deficiency, or viral infection in the opinion of the investigator
known hypersensitivity to pacritinib or any of the following inactive ingredients: microcrystalline cellulose, polyethylene glycol, and magnesium stearate; any contraindication to the ""physician's choice"" medicinal product selected by the investigator to be used as the comparator or to loperamide or equivalent antidiarrheal medication.",1,0,0,1,0,0,18.0,200.0,Pleura,Pleura,0,0,All
106,106,106,686,NCT03172299,2023-10-27,prevention of neovascular glaucoma by intravitreal injections of anti-vegf in patients treated with proton therapy for a large choroidal melanoma,prevention of neovascular glaucoma by intravitreal injections of anti-vascular endothelial growth factor in patients treated with proton therapy for a large choroidal melanoma,PROTECT,interventional,"the reference treatment of ocular melanoma is a conservative treatment by proton therapy. its goal is to treat the tumor while preserving the eyeball and visual acuity. however, ablation of the eyeball is sometimes necessary after proton therapy in the case of neovascular glaucoma. this complication occurs in 7 to 47% of cases (depending on the size of the tumor) and is associated with hypersecretion of vascular endothelial growth factor (vegf) related to necrotic and inflammatory tumor tissue after proton therapy or ischemic retina. the intravitreal injections of anti-vegf are used in the treatment of neovascular radicular glaucoma without avoiding enucleation in all cases. the investigators propose to study the prevention of neovascular glaucoma by intravitreal prophylactic administration of anti-vegf.","inclusion criteria:

age ≥ 18 years
choroid melanoma more than 7mm thick and / or over basal diameter of 15mm treated by proton therapy

exclusion criteria:

iris melanoma
melanoma immediately metastatic
pregnant or breastfeeding women
known hypersensitivity to aflibercept (anti-vegf selected)",1,0,0,1,0,0,18.0,200.0,Brain,Brain,0,1,All
107,107,107,689,NCT03175224,2023-10-19,apl-101 study of subjects with nsclc with c-met exon 14 skip mutations and c-met dysregulation advanced solid tumors,"phase 1 / 2 multicenter study of the safety, pharmacokinetics, and preliminary efficacy of apl-101 in subjects with non-small cell lung cancer with c-met exon 14 skip mutations and c-met dysregulation advanced solid tumors",SPARTA,interventional,"to assess:

efficacy of apl-101 as monotherapy for the treatment of nsclc harboring met exon 14 skipping mutations, nsclc harboring met amplification, solid tumors harboring met amplification, solid tumors harboring met fusion, primary cns tumors harboring met alterations, solid tumors harboring wild-type met with overexpression of hgf and met
efficacy of apl-101 as an add-on therapy to egfr inhibitor for the treatment of nsclc harboring egfr activating mutations and developed acquired resistance with met amplification and disease progression after documented cr or pr with 1st line egfr inhibitors (egfr-i)","major inclusion criteria:

men and women 18 years of age or older.

9 cohorts will be enrolled:

cohort a1 / exon 14 nsclc met inhibitor naive in first line: histologically or cytologically confirmed nsclc with exon 14 skipping mutations; all histologies; unresectable or metastatic disease (stage 3b/4); treatment-naive subjects in first line; not received any met inhibitor and no known met kinase inhibitor resistance mutations
cohort a2 / exon 14 nsclc - met inhibitor naïve: histologically or cytologically confirmed nsclc with exon 14 skipping mutations; all histologies; unresectable or metastatic disease (stage 3b/4); pretreated subjects refractory to or intolerant of standard therapies with no more than three lines of prior therapy in the unresectable or metastatic setting; not received any met inhibitor and no known met kinase inhibitor resistance mutations
cohort b / exon 14 nsclc met inhibitor experienced: enrollment completed
cohort c / met amplification basket tumor types excluding primary cns tumors: any solid tumor type regardless of histology excluding primary cns tumors, with met amplification; unresectable or metastatic disease, refractory to or intolerant of standard therapies, or refused standard therapies, or if therapy was unavailable or unfeasible, with no more than 3 prior lines of therapy in the unresectable or metastatic setting; not received any met inhibitor and no known met kinase inhibitor resistance mutations
cohort c1 / met amplification and wild-type egfr nsclc: nsclc regardless of histology, harboring met amplification and wild-type egfr; unresectable or metastatic disease, previously untreated or treated with no more than 3 prior lines of therapy in the unresectable or metastatic setting; not received any met inhibitor and no known met kinase inhibitor resistance mutations
cohort c2 / egfr positive nsclc with acquired met amplification (apl-101 add-on therapy): unresectable or metastatic nsclc regardless of histology, harboring egfr activating mutations with acquired met-amplification as resistance mechanism to the egfr-i; developed resistance to first-line egfr-inhibitor therapy after an initial response (documented pr for at least 12 weeks); radiological documentation of disease progression per recist on first-line egfr inhibitor therapy; currently on an egfr-inhibitor therapy and agrees to receive apl-101 as an add-on therapy during the study; no history of interstitial lung disease (ild)/pneumonitis, grade ≥3 liver toxicity or qt prolongation with egfr-i therapy; not received any met inhibitor and no known met kinase inhibitor resistance mutations
cohort d / met fusion basket tumor types excluding primary cns tumors: any solid tumor type regardless of histology excluding primary cns tumors; unresectable or metastatic disease, refractory to or intolerant of standard therapies, or refused standard therapies, or if therapy was unavailable or unfeasible, with no more than 3 prior lines of therapy in the unresectable or metastatic setting; not received any met inhibitor and no known met kinase inhibitor resistance mutations
cohort e / primary cns tumors with met alterations: subjects with primary cns tumors who meet inclusion criteria of met dysregulations defined as single or co-occurred met fusion including ptprz1-met (zm) fusion, met exon 14 skipping mutations, or met amplification; refractory to or intolerant of standard therapies, or refused standard therapies, or if therapy was unavailable or unfeasible, with no more than 3 prior lines of therapy in the unresectable or metastatic setting; not received any met inhibitor and no known met kinase inhibitor resistance mutations; neurological symptoms controlled on a stable/decreasing dose of steroids for at least 2 weeks before c1d1
cohort f / basket tumor types harboring wild-type met with over-expression of hgf and met: any solid tumor type regardless of histology harboring wild-type met with overexpression of hgf and met; unresectable or metastatic disease, refractory to or intolerant of standard therapies, or refused standard therapies, or if therapy was unavailable or unfeasible, with no more than 3 prior lines of therapy in the unresectable or metastatic setting; not received any met inhibitor and no known met kinase inhibitor resistance mutations
treated or untreated asymptomatic parenchymal cns disease or leptomeningeal disease is allowed.
presence of ≥1 measurable lesion (scan done ≤28 days of c1d1) to serve as target lesion according to relevant criteria
ecog performance status of 0-1. for subjects with primary cns tumors, kps score ≥70.
acceptable organ function
for all prior anticancer treatment, a duration of 30 days or 5 half-lives of the agents used, whichever is shorter, must have elapsed, and any encountered toxicity must have resolved to levels meeting all the other eligibility criteria prior to the first dose of study treatment. palliative radiotherapy to non-target lesions should be completed within 2 weeks prior to apl-101 administration.
adequate cardiac function
women of child-bearing potential must have a negative serum or beta-hcg at screening or evidence of surgical sterility or evidence of post-menopausal status
no planned major surgery within 4 weeks of first dose of apl-101
expected survival (life expectancy) ≥ 3 months from c1d1
provision of sample; e.g. archival or a fresh tumor biopsy sample (if safe and feasible) either from the primary or a metastatic site) or liquid biopsy sample (if tumor tissue is insufficient or lacking, and approved by the sponsor) is required for prospective central lab confirmation for study entry (subjects with previously confirmed molecular status by the sponsor designated central lab or fda approved ngs based met testing may be exempted, subjected to sponsor approval.

major exclusion criteria:

hypersensitivity to apl-101, excipients of the drug product, or other components of the study treatment regimen.
known actionable mutation/gene rearrangement of egfr (except for nsclc subjects in cohort c and c-2), alk, ros1, ret, ntrk, kras, and braf.
use or intended use of any other investigational product, including herbal medications, through study treatment termination.
active uncontrolled systemic bacterial, viral, or fungal infection or clinically significant, active disease process, which in the opinion of the investigator makes the risk: benefit unfavorable for the participation of the trial.
life-threatening illness, significant organ system dysfunction or comorbid conditions, or other reasons that, in the investigator's opinion, could compromise the subject's safety or the integrity of the study outcomes, or interfere with the absorption or metabolism of apl-101.
unstable angina or myocardial infarction within 1 year prior to first dose of apl-101, symptomatic or unstable arrhythmia requiring medical therapy, history of congenital prolonged qt syndrome, prolonged qt interval corrected by fridericia formula (qtcf) at screening, or concurrent treatment with a medication that is a known risk for prolonging the qt interval. chronic controlled atrial fibrillation is not excluded.
historical seropositive results consistent with active infection for hepatitis c virus (hcv) or hepatitis b virus (hbv) with high viral loads not actively managed with antiviral therapy and human immunodeficiency virus (hiv) positive subjects who are not clinically stable or controlled on their medication (asymptomatic subjects with cd4+ t-cell (cd4+) counts ≥ 350 cells/μl and have not had an opportunistic infection within the past 12 months prior to first dose of apl-101 would be eligible for study entry. if history is unclear, relevant test(s) at screening will be required to confirm eligibility.
known significant mental illness or other conditions such as active alcohol or other substance abuse that, in the opinion of the investigator, predisposes the subject to high risk of noncompliance with the protocol treatment or assessments.
unable to swallow orally administered medication whole.
impairment of gastrointestinal function or gastrointestinal disease that may significantly alter drug absorption
women who are breastfeeding

history of another malignancy within 3 years prior to c1d1. a subject with the following malignancies is allowed if considered cured or unlikely to recur within 3 years:

carcinoma of the skin without melanomatous features.
curatively treated cervical carcinoma in situ.
bladder tumors considered superficial such as noninvasive (t1a) and carcinoma in situ (t1s), thyroid papillary cancer with prior treatment, prostate cancer which has been surgically or medically treated and not likely to recur within 3 years.
subjects who are unable or unwilling to discontinue excluded medications (drugs with known qtc risk and known strong cytochrome p450 [cyp]3a4 inducer and/or strong inhibitors) for at least 5 half-lives prior to first dose of study drug. subjects may qualify if such medication(s) can be safely replaced with alternate medications with less risk of drug-drug interaction.
subjects with active covid-19 infection.
symptomatic and/or neurologically unstable cns metastases, or who require an increase in steroid dose to control cns disease. subjects who have been receiving a stable steroid dose for at least 2 weeks prior to c1d1 may be allowed.",1,0,1,0,0,0,18.0,200.0,Brain,Lung,0,0,All
108,108,108,690,NCT03178552,2023-11-02,a study to evaluate the efficacy and safety of multiple targeted therapies as treatments for participants with non-small cell lung cancer (nsclc),a phase ii/iii multicenter study evaluating the efficacy and safety of multiple targeted therapies as treatments for patients with advanced or metastatic non-small cell lung cancer (nsclc) harboring actionable somatic mutations detected in blood (b-fast: blood-first assay screening trial),B-FAST,interventional,"this is a phase 2/3, global, multicenter, open-label, multi-cohort study designed to evaluate the safety and efficacy of targeted therapies or immunotherapy as single agents or in combination in participants with unresectable, advanced or metastatic nsclc determined to harbor oncogenic somatic mutations or positive by tumor mutational burden (tmb) assay as identified by two blood-based next-generation sequencing (ngs) circulating tumor dna (ctdna) assays.","inclusion criteria:

histologically or cytologically confirmed diagnosis of unresectable stage iiib not amenable to treatment with combined modality chemoradiation (advanced) or stage iv (metastatic) nsclc
eastern cooperative oncology group (ecog) performance status 0-2
measurable disease
adequate recovery from most recent systemic or local treatment for cancer
adequate organ function
life expectancy greater than or equal to (>/=) 12 weeks
for female participants of childbearing potential and male participants, willingness to use acceptable methods of contraception

exclusion criteria:

inability to swallow oral medication
women who are pregnant or lactating
symptomatic, untreated cns metastases
history of malignancy other than nsclc within 5 years prior to screening with the exception of malignancies with negligible risk of metastasis or death
significant cardiovascular disease, such as new york heart association cardiac disease (class ii or greater), myocardial infarction, or cerebrovascular accident within 3 months prior to randomization, unstable arrhythmias, or unstable angina
known human immunodeficiency virus (hiv) positivity or autoimmune deficiency syndrome (aids)-related illness
either a concurrent condition or history of a prior condition that places the patient at unacceptable risk if he/she were treated with the study drug or confounds the ability to interpret data from the study
inability to comply with other requirements of the protocol",1,0,1,1,0,0,18.0,200.0,Lung,Lung,0,1,All
109,109,109,699,NCT03194893,2023-11-01,a rollover study of alectinib in patients with anaplastic lymphoma kinase (alk)-positive or rearranged during transfection (ret)-positive cancer,"a multicenter, international, rollover study of alectinib in patients with anaplastic lymphoma kinase (alk)-positive or rearranged during transfection (ret)-positive cancer",,interventional,the purpose of this study is to provide continued treatment with alectinib or crizotinib as applicable to participants with alk- or ret positive cancer who were previously enrolled in any roche-sponsored alectinib study and who are deriving continued clinical benefit from alectinib or crizotinib in the parent trial at the time of parent trial closure.,"inclusion criteria:

participants enrolled in a roche-sponsored alectinib trial who are experiencing a clinical benefit from alectinib or crizotinib treatment at the time of discontinuation from the parent trial and for whom a switch to commercial supply is not feasible
collected study termination data, including efficacy and safety data, as required by the parent study on the electronic case report form (ecrf)
for women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use single or combined contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 3 months after the last dose of study drug
for men: agreement to remain abstinent or use a contraceptive method that results in a failure rate of < 1% per year during the treatment period and for at least 3 months after the last dose of study drug.

exclusion criteria:

evidence of lack of clinical benefit in parent trial during the screening phase of this rollover study
permanent discontinuation of alectinib or crizotinib for any reason during the parent study or before first dose of study drug in the rollover study
evidence of an adverse event for which the parent protocol stipulates permanent discontinuation
pregnant or breastfeeding women
ongoing serious adverse event that has not resolved to baseline level or grade ≤1 prior to first dose of study treatment in the rollover study
treatment interruption for more than 21 days due to an adverse event since the last administration of alectinib or crizotinib in the parent trial. any ongoing adverse events that require temporary treatment interruption must be resolved to baseline grade or assessed as stable and not requiring further treatment interruption by the investigator
administration of strong/potent cytochrome p450 (cyp) 3a inhibitors or inducers within 14 days prior to the first dose of treatment on this study and while on treatment with crizotinib
any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol requirements and/or follow-up procedures; these conditions should be discussed with the participant before trial entry",1,0,0,1,0,0,0.0,200.0,Pleura,Pleura,0,1,All
110,110,110,701,NCT03212404,2023-08-28,phase 1 study of ck-301 (cosibelimab) as a single agent in subjects with advanced cancers,"a phase 1, open-label, multicenter, dose-escalation study of ck-301 administered intravenously as a single agent to subjects with advanced cancers",,interventional,"ck-301 (cosibelimab) is a fully human monoclonal antibody of igg1 subtype that directly binds to programmed death-ligand 1 (pd-l1) and blocks its interactions with the programmed death-1 (pd-1) and b7.1 receptors. the primary objectives of this study are to assess the safety, tolerability and efficacy of ck-301 when administered intravenously as a single agent to subjects with selected recurrent or metastatic cancers.","inclusion criteria:

signed written informed consent.
male or female subjects aged greater than or equal to 18 years.
for nsclc: histologically or cytologically confirmed diagnosis of unresectable recurrent or metastatic non-small cell lung cancer.
for crc: histologically confirmed diagnosis of recurrent or metastatic colorectal cancer assessed as microsatellite instability-high (msi-h) or mismatch repair deficient (dmmr).
for ec: histologically or cytologically confirmed advanced, recurrent or metastatic endometrial carcinoma.
for cscc: histologically confirmed diagnosis of unresectable or metastatic cutaneous squamous cell carcinoma not amenable to local therapy.
for sclc: histologically or cytologically confirmed diagnosis of unresectable small cell lung cancer.
for mpm: histologically or cytologically confirmed diagnosis of unresectable malignant pleural or peritoneal mesothelioma.
for hnscc: histologically or cytologically confirmed diagnosis of recurrent or metastatic hnscc (oral cavity, pharynx, larynx), stage iii/iv and not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy).
for mel: histologically confirmed diagnosis of unresectable stage iii or metastatic melanoma not amenable to local therapy (excluding uveal or ocular melanoma).
for mcc: histologically confirmed diagnosis of metastatic merkel cell carcinoma not amenable to local therapy.
for rcc: histologically confirmed diagnosis of renal cell carcinoma (with clear cell component) with advanced or metastatic disease that is not amenable to cure by surgery or other means.
for uc: histologically or cytologically documented locally advanced or metastatic transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, urethra) not amenable to cure by surgery or other means.
for hl: histologically confirmed primary diagnosis of classical hodgkin's lymphoma.
for b-cell nhl: histologically confirmed diagnosis of non-hodgkin lymphoma.
eastern cooperative oncology group (ecog) performance status of 0 to 1 at trial entry and an estimated life expectancy of at least 3 months
must have at least one measurable lesion based on recist 1.1.
have provided a formalin fixed tumor tissue sample from a biopsy of a tumor lesion either at the time of or after the diagnosis of metastatic disease has been made and from a site not previously irradiated.
adequate hematological, hepatic and renal function as defined in the protocol.
effective contraception for both male and female subjects if the risk of conception exists.
other protocol defined inclusion criteria could apply.

exclusion criteria:

prior therapy with an anti-pd-1, anti-pd-l1, anti-pd-l2, anti-cd137, anti-ctla-4 antibody, or any other antibody or drug specifically targeting t-cell co-stimulation or immune checkpoint pathways.
concurrent treatment with a non-permitted drug.
history of severe hypersensitivity reactions to other monoclonal antibodies.
prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast, or localized prostate cancer.
chemotherapy, radioactive, biological cancer therapy, or tyrosine kinase inhibitor (tki) therapy, within four weeks prior to the first dose of study drug, or who has not recovered to nci ctcae grade 1 or better from the aes due to cancer therapeutics administered more than four weeks earlier.
significant acute or chronic infections as defined in the protocol.
active or history of interstitial lung disease (ild), or has had a history of pneumonitis that has required oral or iv steroids.
active or suspected autoimmune disease or a documented history of autoimmune disease.
known current drug or alcohol abuse.
underlying medical conditions that will make the administration of study drug hazardous or obscure the interpretation of toxicity determination or adverse events.
use of other investigational therapy within 28 days before study drug administration.
pregnant or breastfeeding.
uncontrolled or significant cardiovascular disease.
psychiatric illness or social situation that would preclude study compliance.
receipt of live, attenuated vaccine within 28 days prior to the first dose of study drug.",1,1,0,0,0,0,18.0,200.0,Pleura,Pleura,0,0,All
111,111,111,703,NCT03212742,2023-09-12,phase i/iia study of concomitant radiotherapy with olaparib and temozolomide in unresectable high grade gliomas patients,phase i/iia study of concomitant radiotherapy with olaparib and temozolomide in unresectable high grade gliomas patients,OLA-TMZ-RTE-01,interventional,"the stupp protocol is the standard treatment of glioblastoma multiform (gbm) which prognosis remains poor.

the non-dividing nature of normal brain cells provides an opportunity to enhance the therapeutic ratio by combining radiation with inhibitors of replication-specific dna repair pathways such poly(adp-ribose) polymerase (parp) inhibitors, thus inducing more cytotoxic effects of dna-damage related to treatment modalities, including alkylating reagents like temozolomide (tmz).

olaparib, a potent parp inhibitor, overcomes apoptotic resistance and sensitizes gbm cells for death receptor-mediated apoptosis induced by trail (tumor necrosis factor-related apoptosis inducing ligand). moreover, inhibition of parp activity increases cellular sensitivity to ionizing radiation: it was even suggested to be more pronounced in tumors than in normal tissue.

lastly, progress in technical imaging and intensity-modulated-radiotherapy (imrt) techniques provide new possibilities for sparing healthy tissues.","inclusion criteria:

provision of signed informed consent prior to any study specific procedures
histologically-confirmed diagnosis of glioblastoma (idh-wildtype, idh-mutant or nos, except gliosarcoma), non resectable or partially resectable with a residual tumor on pre-radiotherapy mri. the presence of a residual disease will be assessed by the radiologist on the pre-radiotherapy imaging as compared with initial imaging.
imrt must start within 6 weeks after histological diagnosis
age between 18 and 70 years ;
neurologically asymptomatic or pauci-symptomatic patients. patients with moderated neurological symptoms without systemic corticosteroids treatment or with a stable dose of corticosteroids during the study as long as these were started at least 4 weeks prior to treatment can be included.

adequate bone marrow and organ function measured within 15 days prior to administration of study treatment as defined below:

haemoglobin ≥ 10.0 g/dl with no blood transfusions (packed red blood cells and platelet transfusions) in the past 28 days before start of treatment

absolute neutrophil count (anc) ≥ 1.5 x 109/l

o no features suggestive of mds/aml on peripheral blood smear

platelet count ≥ 100 x 109/l
white blood cells (wbc) > 3x109/l
total bilirubin ≤ 1.5 x institutional upper limit of normal
ast (sgot)/alt (sgpt) ≤ 2.5 x institutional upper limit of normal
creatinine clearance estimated using the cockcroft-gault equation of ≥51 ml/min:

estimated creatinine clearance = [(140-age(years)) x weight(kg) (x fsex) ] / [serum creatinine (mg/dl) x 72] where fsex=0.85 for females and fsex=1 for males.

ecog performance status 0-2
patients must have a life expectancy ≥ 16 weeks.
women of childbearing potential (wocbp) and men under efficient contraception during treatment and at least 6 months after the end of treatment.
evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on day 1.

postmenopausal (if applicable) is defined as:

amenorrheic for 1 year or more following cessation of exogenous hormonal treatments,
lh and fsh levels in the post-menopausal range for women under 50,
radiation-induced oophorectomy with last menses >1 year ago,
chemotherapy-induced menopause with >1 year interval since last menses,
or surgical sterilisation (bilateral oophorectomy or hysterectomy).
male patients and their partners, who are sexually active and of childbearing potential, must agree to the use of two highly effective forms of contraception in, throughout the period of taking study treatment and for 3 months after last dose of study drug(s) to prevent pregnancy in a partner.
patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
subjects affiliated to an appropriate social security system

exclusion criteria:

any prior radiotherapy to brain
any prior chemotherapy or immunotherapy
involvement in the planning and/or conduct of the study (applies to both astrazeneca staff and/or staff at the study site)
candidate for a concomitant therapy with tumor-treating fields during the maintenance treatment [70]
previous enrolment in the present study
participation in another clinical trial protocol within 30 days prior to enrolment;
any previous treatment with a parp inhibitor, including olaparib.
patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years
gadolinium hypersensitivity, or any contraindication to undergo mri examination (pacemaker, brain aneurysms clips)
patients who had no initial pre-surgery contrast enhanced mri scan including the standard sequences (t1 non enhanced, t1 contrast enhanced, t2 flair)
patients receiving any systemic chemotherapy, radiotherapy (except for palliative reasons), within 2 weeks from the last dose prior to study treatment. the patient can receive a stable dose of bisphosphonates for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment with study drug.
concomitant use of known strong cyp3a inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted) or moderate cyp3a inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). the required washout period prior to starting olaparib is 2 weeks.
concomitant use of known strong (eg. phenobarbital, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, and st john's wort ) or moderate cyp3a inducers (eg. bosentan, modafinil). the required washout period prior to starting olaparib is 5 weeks for phenobarbital and 3 weeks for other agents.
resting ecg with qtc > 470 msec detected on 2 or more time points within a 24 hour period or family history of long qt syndrome. if ecg demonstrates qtc > 470 msec, patient will be eligible only if repeat ecg demonstrates qtc ≤470 msec;
blood transfusions within 1 month prior to study start
previous allogenic bone marrow transplant or double umbilical cord blood transplantation (ducbt)
patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of mds/aml.
major surgery within 14 days of starting study treatment and patients must have recovered from any effects of any major surgery.
patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression (untreated and unstable for at least 28 days prior to study entry), superior vena cava syndrome, extensive bilateral lung disease on hrct scan or any psychiatric disorder that prohibits obtaining informed consent.
patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication (inflammatory bowel disease, major bowel resection …)
pregnant or breast feeding women.
immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (hiv) and are receiving antiviral therapy.
patients with known active hepatitis (i.e., hepatitis b or c) due to risk of transmitting the infection through blood or other body fluids.
patients with a known hypersensitivity to olaparib or any of the excipients of the product.
for temozolomide treatment, patients with a known galactose intolerance, a lapp lactase deficit or a glucose or galactose malabsorption syndrome (rare hereditary diseases)
patients with uncontrolled epileptic seizures.
neurological, addictive or psychiatric disorder;
lack of availability for clinical follow-up assessments;
persons protected by a legal regime (guardianship, trusteeship).",1,1,1,0,0,0,18.0,70.0,Pleura,Pleura,0,0,All
112,112,112,704,NCT03215030,2023-09-20,a study of modakafusp alfa on adult participants with relapsed/refractory multiple myeloma,"a phase 1/2 open-label study to investigate the safety and tolerability, efficacy, pharmacokinetics, and immunogenicity of modakafusp alfa (tak-573) as a single agent in patients with relapsed refractory multiple myeloma",iinnovate-1,interventional,"the main aims of this 3-part study are as follows:

part 1: to determine any side effects from modakafusp alfa single treatment and how often they occur. the dose of modakafusp alfa will be increased a little at a time until the highest dose that does not cause harmful side effects is found.

part 2: to assess clinical activity of one or more dosing schedules of modakafusp alfa alone in participants with relapsed/refractory multiple myeloma. dexamethasone standard dose will be administered with one or more selected dose of modakafusp alfa in selected group of participants.

part 3: to find the optimal dose with the more favorable risk-benefit profile of modakafusp alfa.

participants will receive modakafusp alfa at one of two doses which will be given through a vein.","inclusion criteria:

for parts 1 and 2:

1. has mm defined by the imwg criteria with evidence of disease progression and:

in need of additional myeloma therapy as determined by the investigator.
has previously received at least 3 lines of myeloma therapy (for example, containing an immunomodulatory imide drug [imid], a proteasome inhibitor [pi], an alkylating agent, and/or an anti-cd38 as single agents or in combination).
is either refractory to or intolerant of at least 1 pi and a least 1 imid.

for part 3:

has mm defined by the imwg criteria with evidence of disease progression and:

in need of additional myeloma therapy as determined by the investigator.
has previously received at least 3 lines of myeloma therapy.
is refractory to at least 1 imid (ie, lenalidomide or pomalidomide [thalidomide excluded]), at least 1 pi (ie, bortezomib, ixazomib, or carfilzomib), and refractory to at least 1 anti-cd38 antibody (ie, daratumumab or isatuximab) and has demonstrated disease progression with the last therapy. participants who are primary refractory, meaning they never achieved at least a mr with any previous treatment line, are not eligible.

for participants in part 2 and 3 only: measurable disease is defined as :

serum m-protein ≥500 mg/dl (≥5 g/l)
urine m-protein ≥200 mg/24 hours.
serum free light chain (flc) assay, with involved flc level ≥10 mg/dl (≥100 mg/l) provided serum flc ratio is abnormal.
during part 1 only, participants not meeting the above criteria for measurable disease should, at least, have measurable bone marrow plasmacytosis (greater than or equal to [≥ ] 10 percent [%]) and/or plasmacytoma (≥1 centimeter [cm] in diameter) detected by physical examination or imaging.
eastern cooperative oncology group (ecog) performance status of ≤2.

exclusion criteria:

for parts 1 and 2:

has polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (poems) syndrome, monoclonal gammopathy of unknown significance, smoldering myeloma, solitary plasmacytoma, amyloidosis, waldenstrom macroglobulinemia or immunoglobulin m (igm) myeloma, or lymphoplasmacytic lymphoma (lpl).
who have received autologous stem cell transplant (sct) 60 days before first infusion of modakafusp alfa or participants who have received allogeneic sct 6 months before first infusion. graft-versus-host disease that is active or requires ongoing systemic immunosuppression.
has not recovered from adverse reactions to prior myeloma treatment or procedures (chemotherapy, immunotherapy, radiation therapy) to nci ctcae less than or equal to (≤) grade 1 or baseline, except for sensory or motor neuropathy which should have recovered to ≤ grade 2 or baseline.
has clinical signs of central nervous system involvement of mm.

for part 3:

hepatitis b virus (hbv) or hepatitis c virus (hcv) infection. seropositive for hepatitis b (defined by a positive test for hepatitis b surface antigen [hbsag]. participants with resolved infection (that is, participants who are hbsag negative but positive for antibodies to hepatitis b core antigen [anti-hbc] and/or antibodies to hepatitis b surface antigen [anti-hbs]) must be screened using real-time polymerase chain reaction (pcr) measurement of hbv dna levels. those who are pcr positive will be excluded.
in addition to the above criteria, participants must not have plasma cell leukemia or have had primary refractory mm, current central nervous system involvement of mm, myelodysplastic syndrome, myeloproliferative syndrome, or have had a second malignancy within the previous 3 years, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, cervical carcinoma in situ, resected colorectal adenomatous polyps, breast cancer in situ, or other malignancy for which the participant is not on active anticancer therapy.",1,1,1,0,0,0,18.0,200.0,Pleura,Pleura,0,0,All
113,113,113,714,NCT03222635,2021-01-12,prospective endoscopic follow-up of patients with submucosal esophageal adenocarcinoma (the prefer trial),endoscopic management of patients with t1bn0m0 esophageal adenocarcinoma: a prospective multicenter registry.,,interventional,aim of this prospective multicenter study is to evaluate the safety of an endoscopic follow-up strategy in patients treated with endoscopic resection (er) for submucosal or high-risk mucosal esophageal adenocarcinoma (t1bn0m0 or hr t1an0m0 eac).,"inclusion criteria:

patients with submucosal or high-risk mucosal eac diagnosed in an er specimen, revised by a panel of expert gastrointestinal (gi) pathologists.
signed informed consent.

exclusion criteria:

prior history of high-risk mucosal or ≥t1sm.
synchronous esophageal squamous cell carcinoma.
suspicion on lymph node metastasis or distant metastasis on eus, ultrasound of the neck or ct-thorax-abdomen performed six weeks after er during baseline measurement.
tumor-positive deep resection margin (r1) in er specimen.
patients unable to give signed informed consent.",1,0,0,0,0,1,18.0,200.0,Pleura,Gastric,0,0,All
114,114,114,717,NCT03232268,2021-10-11,hla-mismatched microtransplantation without immunosuppressive treatment in patients with myeloid hemopathies,hla-mismatched microtransplantation without immunosuppressive treatment in patients with myeloid hemopathies,MICROSTEM,interventional,this study aims at evaluating the safety of an approach based on hla-mismatched microtransplantation without immunosuppressive treatment in patients with myeloid hemopathies who are ineligible to conventional allograft,"inclusion criteria:

age> or = 65 years with a myeloid hemopathy in complete remission or complete remission with incomplete hematological recovery or age<65 years with an ineligibility to allograft (contraindication to conditioning)
hla-partially matched family donors
affiliated to(or beneficiary of) the social security
informed consent signed

exclusion criteria:

aml3
previous hematopoietic stem cell transplantation
uncontrolled infection -ps>3 -other progressive cancer
psychiatric disease
vulnerable person or unable to provide informed consent
emergency
unable to comply with required study follow up",1,1,0,0,0,0,18.0,200.0,Lung,Lung,1,0,All
115,115,115,725,NCT03246841,2023-05-10,investigation of tumour spectrum of germline mutations in breast and ovarian cancer genes.,"investigation of tumour spectrum, penetrance and clinical utility of germline mutations in new breast and ovarian cancer susceptibility genes.",TUMOSPEC,interventional,"tumospec is a national family study designed to measure the relative and absolute risk of cancer for carriers of deleterious mutations to these ""new"" breast cancer (bc) susceptibility genes. index cases will be enrolled consecutively from patients attending an appointment at one of the unicancer centres, with no other inclusion criteria, and offered a brca1/2 analysis as part of their care plan. a panel of 24 tumospec genes, chosen in advance by a steering committee, will be tested as the same time as the brca1/2 genes, at one of the usual brca1/2 analysis laboratories belonging to the same network and participating in the study. if a mutation is found, the index cases will be asked to invite their first and second degree family members and their cousins to take part in the study, regardless of whether they have cancer. saliva samples will be then taken and used for a targeted analysis of the familial abnormality. each participant will also complete an epidemiological questionnaire in order to gather information about his/her medical history and any exposure to various risk factors. all medical and genotype data will be centralised at the genetic epidemiology research platform (pige, inserm). the cumulative mutation frequency for all genes is estimated at 10%. penetrance will be analysed using methods designed to minimise selection bias. the expression spectrum of the mutations will also be described. for genes where the number of mutated families is too low, the data may be contributed to international consortia. the main project will be preceded by a two-year feasibility study, using the same inclusion criteria and logistic circuits. it is this pilot study to which the current funding application relates.","inclusion criteria:

index case eligibility:

any person with an indication for a brca1/brca2 gene analysis and who has been offered tumospec panel screening.

age ≥18 years.

family member eligibility:

family members will be eligible if the mutation identified in the index case is considered deleterious.

any family member to the first and second decree or a cousin of the index case. family members from both sides of the family will be invited to take part.

age ≥18 years.

exclusion criteria:

people deprived of their civil liberties or who are under judicial protection or guardianship.

patients unable to answer the questionnaire for social or psychological reasons.

children of the index cases, of any age.",1,0,0,0,0,1,18.0,75.0,Breast,Breast,0,0,All
116,116,116,729,NCT03250338,2021-04-28,study investigating the efficacy of crenolanib with chemotherapy vs chemotherapy alone in r/r flt3 mutated aml,"phase iii randomized, double-blind, placebo-controlled study investigating the efficacy of the addition of crenolanib to salvage chemotherapy versus salvage chemotherapy alone in subjects ≤ 75 years of age with relapsed/refractory flt3 mutated acute myeloid leukemia",,interventional,"this is a randomized, multi-center, double-blind, placebo-controlled study designed to evaluate the efficacy of crenolanib administered following salvage chemotherapy, consolidation chemotherapy, post bone marrow transplantation and as maintenance in relapsed/refractory aml subjects with flt3 activating mutation.","inclusion criteria:

confirmed diagnosis of aml according to world health organization (who) 2016 classification
presence of flt3-itd and/or d835 mutation(s)
subjects must be primary refractory or relapsed to 1st line intensive treatment for aml or refractory or relapsed after second line of treatment for aml
age ≥ 18 years and ≤ 75 years
adequate hepatic function
adequate renal functions
ecog performance status ≤ 3

exclusion criteria:

known clinically active central nervous system(cns) leukemia
severe liver disease
known, active infection with hepatitis b virus (hbv) or hepatitis c virus (hcv)
prior anti-leukemia therapy within the 14 days prior to randomization. prior use of quizartinib or gilteritinib must be discontinued 21 days prior to randomization. prior use of hydroxyurea or other palliative treatment for leukocytosis is allowed.
previous treatment with crenolanib or prior participation in clinical trial involving crenolanib.",1,0,0,1,0,0,18.0,75.0,Other,Pleura,0,0,All
117,117,117,730,NCT03250390,2022-11-07,breath analysis to diagnose lung cancer,analysis of volatile organic compounds in exhaled air as a diagnostic tool for thoracic cancers,CATOCOV,interventional,determination of volatile organic compounds to discriminate patients with lung cancer from healthy smokers and non-smokers healthy subjects.,"inclusion criteria:

patients with histologically proven lung cancer

controls:

healthy smoker or non-smoker subjects
without respiratory diseases excepted chronic obstructive pulmonary disease.

exclusion criteria:

history of cancer other than lung cancer within 5 years before inclusion
oral or facial malformation
incomprehension of maneuvers for the collection",1,0,0,0,0,1,18.0,200.0,Lung,Lung,0,0,All
118,118,118,738,NCT03256084,2021-05-05,tumoral circulating cells and colorectal cancer progression,characterization of tumoral circulating cells according to stage of progression of colorectal cancers,,interventional,prospective research of circulating tumor cells as markers of progression risk in colorectal cancer.,"inclusion criteria:

patient of more than 18 years old
histological diagnosis of colic adenocarcinoma metastatic or not
before any treatment with systemic chemotherapy
patient affiliated to, or beneficiating of the national security
patient having signed informed consent

exclusion criteria:

patient with previous chemothrapy treatment
patient with more than one evolutive tumoral pathology
patient under long-term immunosuppressor treatment
patient with severe infection
pregnant or breasting woman
person in an emergency situation, adult subject to a legal protection measure (a guardian, guardianship or safeguard of justice), or unable of expressing his / her consent.",1,0,0,0,0,1,18.0,200.0,Colon,Colon,0,1,All
119,119,119,741,NCT03260023,2023-08-01,phase ib/ii of tg4001 and avelumab in hpv16 positive r/m cancers,a phase ib/ii trial evaluating the combination of tg4001 and avelumab in patients with hpv-16 positive recurrent or metastatic malignancies.,,interventional,"the study will consist of two parts :

in the phase ib: safety will be assessed in consecutive cohorts of 3 to 6 patients at increasing doses of tg4001 in combination with avelumab according to a 3+3 design. there will be no intra-patient dose escalation.

in the phase ii part 1, evaluation of efficacy and further evaluation of safety of the combination of tg4001 and avelumab will be performed in a single arm of patients with recurrent or metastatic hpv-16 positive advanced malignancies.

in the phase ii part 2, evaluation of efficacy of the combination of tg4001 and avelumab will be performed in a randomized, open-label controlled study comparing tg4001 in combination with avelumab to avelumab alone in patients with hpv-16 positive advanced malignancies.

in both phases, tumor response will be evaluated on local assessment using recist 1.1.

all patients will be followed up until disease progression, death, or unacceptable toxicity, or study withdrawal for any reason, whichever occurs first.","inclusion criteria:

female or male patients, aged at least 18 years (no upper limit of age)
ecog ps 0 or 1
life expectancy of at least 3 months
patients with histologically or cytologically documented metastatic or refractory/recurrent hpv-16 + cancer: cervical, vulvar, vaginal, penile and anal.
disease must not be amenable to curative surgery resection or curative radiotherapy with documented disease progression

prior therapy:

no more than one prior systemic treatment for recurrent /metastatic disease

prior treatment for recurrent or metastatic disease is not required for:

patients with recurrence/progression within 6 months after completion of prior multimodal therapy for localized or locally advanced disease
patients who are unsuitable for platinum-based therapy
patients who refuse chemotherapy or other standard therapies for the treatment of metastatic or recurrent disease
limited hepatic disease for patients with liver metastases at baseline
availability of tumor tissue from biopsy
at least one measurable lesion by ct scan according to recist 1.1.
adequate hematological, hepatic and renal function
negative blood pregnancy test at screening for women of childbearing potential
highly effective contraception for both male and female patients if the risk of conception exists during the study period and for 3 months after the last study treatment administration

exclusion criteria:

prior exposure to cancer immunotherapy including cancer vaccines, any antibody/drug targeting t cell co-regulatory proteins (immune checkpoints)
patients under chronic treatment with systemic corticosteroids or other immunosuppressive drugs for a period of at least 4 weeks and whose treatment was not stopped 2 weeks prior to the first study treatment, with the exception of patients with adrenal insufficiency who may continue corticosteroids at physiological replacement dose, equivalent to ≤ 10 mg prednisone daily. steroids with no or minimal systemic effect (topical, inhalation) are allowed
patients with cns metastases except those with brain metastases treated locally and clinically stable during 4 weeks prior to start of study treatment, and those without ongoing neurological symptoms that are related to the brain localization of the disease
other active malignancy requiring concurrent systemic intervention
patients with previous malignancies other than the target malignancy to be investigated in this trial (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to study entry and no additional therapy is required during the study period
patient with any organ transplantation, including allogeneic stem cell transplantation
known severe hypersensitivity reactions to monoclonal antibodies (grade ≥ 3 nci-ctc), any history of anaphylaxis, or uncontrolled asthma
any known allergy or reaction to eggs, gentamycin or attributed to compounds of similar chemical or biological composition to therapeutic vaccines/immunotherapeutic products
any known allergy or reaction to any component of anti-pd-l1/pd-1 or its excipients
patients with known history or any evidence of active interstitial lung disease / pneumonitis
patients with active, known, or suspected auto-immune disease or immunodeficiency, except type i diabetes mellitus, hypothyroidism only requiring hormone replacement or skin disorders (such as vitiligo, psoriasis) not requiring systemic treatment
clinically significant (that is, active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction (< 6 months prior to enrollment), unstable angina pectoris, congestive heart failure (new york heart association classification class ≥ ii), or serious uncontrolled cardiac arrhythmia requiring medication/active intervention, history of myocarditis

history of uncontrolled intercurrent illness including but not limited to:

hypertension uncontrolled by standard therapies (not stabilized to 150/90 mmhg or lower)
uncontrolled diabetes (e.g., hemoglobin a1c ≥ 8%)
uncontrolled infection",1,1,1,0,0,0,18.0,200.0,Brain,Lung,0,0,All
120,120,120,760,NCT03296150,2023-05-12,adopt-prestage: study evaluating the impact of the program prestage,"adopt-prestage: randomized controlled trial on acceptability, diffusion and impact on treatment adherence and persistence of the prestage program (program for education and support for oral cancer treatments in the elderly) - randomized controlled study evaluating the impact of the program prestage",ADOPT-PRESTAGE,interventional,"as the proportion of oral anticancer treatments is continuously increasing, adherence appears as a major issue for patients' outcomes. poor adherence affects particularly geriatric patients due among others to polypharmacy or cognitive impairment. thus, the need for educational programs in this population has been regularly emphasized.

prestage educational program was built after an external and internal analysis of educational needs in elderly patients treated with oral cancer treatments. it implicates a multidisciplinary educational team (nurses, physicians, pharmacists, psychologists, physiologists, social workers...). six educational workshops were designed with the following endpoints: disease and treatment understanding, treatment management, nutrition and psychological as well as physical well being.

adopt-prestage is a clinical, prospective, interventional, open-label, multicenter, randomized, controlled trial designed to evaluate the impact of prestage program. it is, to the investigators' knowledge, the first randomized controlled trial evaluating the acceptability and impact (adherence, clinical benefit) of an educational program in an elderly cancer population. the primary endpoint of this trial will be to evaluate adherence using an indirect objective adherence measure: the medication event monitoring system (mems). secondary endpoints include quality of life and evaluation of changes in patients' behaviors.","inclusion criteria:

patients older than 70 years,
for which oral anticancer therapy has been initiated within the previous 45 days or will be started within 45 days
for any type of cancer, solid or hematologic, any stage
estimated life expectancy> 6 months
affiliation to social security or equivalent
patients who can answer questionnaires and protocol evaluations
informed consent signed by patients
domiciled within 50 km around the investigating center

exclusion criteria:

for patients with breast cancer, exclusive treatment with hormone therapy
first-generation hormone therapy in prostate cancer
patient not available for regular follow-up whatever the cause (geographic, family, social, psychological)
any serious condition, ie serious physical or mental, leading to a disability permanent and likely to prevent the proper course of treatment
patient deprived of liberty or under guardianship",1,0,0,0,0,1,70.0,200.0,Pleura,Pleura,0,0,All
121,121,121,770,NCT03308604,2021-07-01,aguix gadolinium-based nanoparticles in combination with chemoradiation and brachytherapy,phase i study of aguix gadolinium-based nanoparticles in combination with chemoradiation and brachytherapy in locally advanced cervical cancer,NANOCOL,interventional,"this is a phase 1 clinical trial evaluating the safety, tolerability of escalating doses of aguix-np in combination with radiation and cisplatin in patients with locally advanced cervical cancer. dose escalation will be conducted using the modified toxicity probability interval (mtpi) method.

three dose levels of intravenous aguix nanoparticles will be explored: 20mg/kg (level -1), 30 mg/kg (level 1) and 50 mg/kg (level 2).","inclusion criteria:

patients with histologically confirmed cancer of the uterine cervix: squamous cell carcinoma or adenocarcinoma stage ib2-iva according to the international federation of gynecology and obstetrics classification, regardless of the pelvic lymph node stage. no evidence of metastatic disease. primary staging should include: clinical examination, pelvic mri and 18-fdg pet. a coelioscopic para-aortic lymph node staging should be done in patients without para-aortic lymph node uptake to guide radiotherapy fields in the situation of pelvic lymph node metastases. if there is no pelvic lymph node metastases, para-aortic lymph node dissection is optional.
ecog performance status 0-1.
age between 18 - 70 years.
neutrophils > 2000/mm^3.
hemoglobin > 9 g/l after transfusion if necessary.
platelets > 100,000/mm^3.
creatinine < 1.5 upper limit of normal or calculated creatinine clearance (cockcroft-gault formula) ≥ 60 ml/min.
liver function (got, gpt, alkaline phosphatase and bilirubin) < 1.5 upper limit of normal.
cardiovascular: no clinically relevant cardiovascular disease, no congestive heart failure, no symptomatic coronary artery disease, no poorly controlled cardiac arrhythmia, no myocardial infarction within the past year.
gastrointestinal: no active inflammatory bowel disease, no lack of physical integrity of the upper gastrointestinal tract, no malabsorption syndrome.
women of childbearing potential must have a negative serum pregnancy test within 7 days prior to initiation of treatment.
proteinuria < 2 g/l (200mg/dl) and creatinine clearance ≥ 60 ml/min.
signed informed consent after informing the patient.
patient affiliated to a social security regimen or beneficiary of the same.

exclusion criteria:

other histological types of cervical cancer than those listed in the inclusion criteria or stage ivb.
history of cancer other than basal cell carcinoma within five past years.
prior treatment with radiotherapy, chemotherapy, targeted therapy or immune therapy for cervical cancer or for any cancer within five past years.
prior pelvic radiotherapy or prior surgical treatment for cervical cancer (excluding diagnostic conisation).
pregnancy or breastfeeding.
obesity (body mass index > 30).
history of prior or current psychiatric illness.
nephropathy, regardless of the grade.
peripheral neuropathy ≥ grade 2.
patients with pre-existing hearing impairments.
active infection or other serious underlying pathology that could prevent the patient from receiving the treatment (especially liver or heart conditions).
positive test for hepatitis b virus surface antigen (hbv sag) or hepatitis c virus ribonucleic acid (hcv antibody) indicating acute or chronic infection.
positive test for human immunodeficiency virus (hiv) or known acquired immunodeficiency syndrome (aids).
inclusion in another clinical trial protocol with an experimental molecule (during this study or within 5 years prior to enrollment).
unable to undergo the follow-up required by study for geographical, social or psychological reasons.
contra-indication for magnetic resonance imaging enhanced with gadolinium and/or any contra-indication to the use of cisplatin.
history of allergic reaction to cisplatin or other platinum containing compounds.
concurrent administration of yellow fever vaccine.",1,1,0,0,0,0,18.0,70.0,Pleura,Pleura,0,0,Female
122,122,122,771,NCT03309111,2022-05-10,"study of isb 1342, a cd38/cd3 bispecific antibody, in subjects with previously treated multiple myeloma","a phase 1, first-in-human, multicenter, open-label, two-part dose-escalation and cohort expansion study of single-agent isb 1342 in subjects with previously treated multiple myeloma",,interventional,"the purpose of this study is to assess safety, efficacy, pharmacokinetic (pk)/pharmacodynamic (pd), and immunogenicity with isb 1342 in subjects with relapsed/refractory multiple myeloma.","inclusion criteria:

documented diagnosis of multiple myeloma with measurable disease (serum, urine, or free light chain) per international myeloma working group (imwg) criteria, including non-secretory or oligo-secretory multiple myeloma which has relapsed after or is refractory to prior therapies, including proteasome inhibitors (pis), immunomodulators (imids) and anti-cd38 targeted therapies (daratumumab, isatuximab).
eastern cooperative oncology group (ecog) performance-status score of 2 or less and 1 or less (for france).
adequate hematologic, renal, and hepatic functions
seronegative for hepatitis b antigen; positive hepatitis b tests can be further evaluated by confirmatory tests, and if viral load is negative, the subject can be enrolled.
seronegative for hepatitis c antibody; if positive, then further test for the presence of antigen by hepatitis c virus polymerase chain reaction (hcv pcr). if hcv antigen tests are negative, then the subject can be enrolled.
oxygen saturation level ≥92% on room air.
left ventricular ejection fraction (lvef) ≥50% and no pericardial or pleural effusion at screening

exclusion criteria:

active central nervous system involvement
exposure to daratumumab or isatuximab within 2 months prior to the start of study treatment
active plasma cell leukemia
active infectious disease
clinically significant cardiovascular and respiratory conditions
history of hiv infection
subjects requiring prohibited concomitant medications",1,1,0,0,0,0,18.0,200.0,Pleura,Pleura,1,0,All
123,123,123,772,NCT03311152,2022-06-08,circulating cell-free dna-based epigenetic biomarker msept9 for hepatocellular carcinoma detection in cirrhosis,diagnostic accuracy of the circulating cell-free dna-based epigenetic biomarker msept9 for hepatocellular carcinoma detection among cirrhotic patients: the sept9-cross study,SEPT9-CROSS,interventional,prospective evaluation of the circulating cell-free dna-based epigenetic biomarker (msept9) through a cross-sectional biomarker phase ii design. the aim of the sept9-cross study is to assess the diagnostic accuracy of the plasma msept9 biomarker in a large-scale study of 530 cirrhotic patients recruited in the nancy university hospital.,"inclusion criteria

patient aged 18 and over.
patient with a diagnosis of cirrhosis (alcohol, hbv, hbc, nash, hemochromatosis, autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis) with or without hepatocellular carcinoma (for each arm).
affiliation to the french social security system (health insurance)

non-inclusion criteria for cases :

malignant liver tumor other than hcc: cholangiocarcinoma, hepatic metastasis of a carcinoma (e.g., colorectal adenocarcinoma);
history of hcc treated by surgical resection, focal destruction [radiofrequency, stereotactic radiotherapy (cyberknife®)], arterial chemoembolization, or radioembolization within the last five years.

non-inclusion criteria for cases and controls:

legal protection measures;
pregnant woman;
hemodialysis, ongoing (possibility of interference with the test);
presence of associated cancer (e.g., colorectal adenocarcinoma, urothelial carcinoma, breast carcinoma, etc.) since less than five years;
presence of a hematological malignancy (no time limit).",1,0,0,0,0,1,18.0,200.0,Pleura,Pleura,0,1,All
124,124,124,773,NCT03313206,2023-05-17,neoadjuvant treatment associated with maintenance therapy by anti-pd1 immunotherapy in patients with resectable head and neck mucosal melanoma,phase ii multicentric study: efficacy evaluation of neoadjuvant treatment associated with maintenance therapy by anti-pd1 immunotherapy on disease-free-survival (dfs) in patients with resectable head and neck mucosal melanoma,IMMUQ,interventional,"the main objective will be to estimate the disease free survival (dfs) of patients with resectable head and neck mucosal melanomas treated by neo-adjuvant anti-pd1 (in combination or not with lenvatinib) followed by surgery, radiotherapy and maintenance immunotherapy in order to compare it to historical dfs results of this kind of patients treated by surgery and radiotherapy. our primary end-point will be disease-free survival at 2 years","inclusion criteria:

be willing and able to provide written informed consent/assent for the trial.
be >/= 18 years of age on day of signing informed consent.
present with a resectable head and neck mucosal melanoma.
be eligible for surgical treatment (without any contraindications).
be eligible for adjuvant radiotherapy.
have measurable disease based on recist 1.1.
be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on day 1. subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the sponsor.
have a performance status of 0 or 1 on the ecog performance scale.
demonstrate adequate organ function as defined in table 1, all screening labs should be performed within 10 days of treatment initiation.
female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

patient affiliated to a social security system or beneficiary of the same

for the cohort b, patients must met the following additional criteria :

not having any contraindication for lenvatinib treatment

exclusion criteria:

is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
has a metastatic disease.
has a non resectable melanoma.
has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (except topical or inhaled steroids) or any other form of immunosuppressive therapy within 2 weeks prior to the first dose of trial treatment.
has a known history of active tb (bacillus tuberculosis)
hypersensitivity to pembrolizumab or any of its excipients.
has had a prior anti-cancer monoclonal antibody (mab) within 4 weeks prior to d1 of study treatment or who has not recovered (i.e., ≤ grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.

has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 4 weeks or 5 half-life times (whatever the shorter) prior to study day 1 or who has not recovered (i.e., ≤ grade 1 or at baseline) from adverse events due to a previously administered agent.

note: subjects with ≤ grade 2 neuropathy are an exception to this criterion and may qualify for the study.
note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
has a known additional malignancy that is progressing or requires active treatment. exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
has known active central nervous system (cns) metastases and/or carcinomatous meningitis. subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
has active autoimmune and/or immune mediated inflammatory disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
has known history of, or any evidence of active, non-infectious pneumonitis.
has an active infection requiring systemic therapy.
has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
has received prior therapy with an anti-pd-1, anti-pd-l1, or anti-pd l2 agent.
has a known history of human immunodeficiency virus (hiv) (hiv 1/2 antibodies).
has known active hepatitis b (e.g., hbsag reactive) or hepatitis c (e.g., hcv rna [qualitative] is detected).
has received a live vaccine within 30 days of planned start of study therapy. note: seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., flu-mist®) are live attenuated vaccines, and are not allowed.
major injuries and/or surgery within the past 4 weeks prior to start of study treatment with incomplete wound healing
has a prior history of organ transplant including allogeneic stem cell transplant
has a lvef below the institutional (or local laboratory) normal range, as determined by multigated acquisition (muga) or echocardiogram (echo)

has an uveal melanoma

for the cohort b, patients must be excluded if one of the following additional criteria is met :

uncontrolled blood pressure (systolic bp>140 mmhg or diastolic bp >90 mmhg) in spite of an optimized regimen of antihypertensive medication
electrolyte abnormalities that have not been corrected
significant cardiovascular impairment: history of congestive heart failure greater than new york heart association (nyha) class ii, unstable angina, myocardial infarction or stroke within 6 months of the first dose of study drug, or cardiac arrhythmia requiring medical treatment at screening
bleeding or thrombotic disorders or subjects at risk for severe hemorrhage. the degree of tumor invasion/infiltration of major blood vessels (e.g. carotid artery) should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy
subjects having > 1+ proteinuria on urine dipstick testing unless a 24-hour urine collection for quantitative assessment indicates that the urine protein is <1 g/24 hours.
subjects who have not recovered adequately from any toxicity from other anti- cancer treatment regimens and/or complications from major surgery prior to starting therapy. withhold lenvatinib for at least 1 week prior to elective surgery. do not administer for at least 2 weeks following major surgery and until adequate wound healing.
the participant has severe hypersensitivity (≥grade 3) to lenvatinib and/or any of its excipients.
has presence of a gastrointestinal condition including malabsorption, gastrointestinal, anastomosis, or any other condition that might affect the absorption of lenvatinib.
has a pre-existing grade ≥3 gastrointestinal or non-gastrointestinal fistula.
has clinically significant hemoptysis or significant tumor bleeding within 2 weeks prior to the first dose of study drug.
prolongation of qtcf interval to >480 ms",1,0,1,0,0,0,18.0,200.0,Pleura,Pleura,0,0,All
125,125,125,774,NCT03313544,2023-04-20,evolution of the heart function when monitoring immunotherapies anti-cancerous inhibiting pd-1,evolution of the heart function when monitoring immunotherapies anti-cancerous inhibiting programmed cell death 1 (pd-1),,interventional,"prospective, monocentric clinical study. patients selected for nivolumab therapy in ap-hm for melanoma and non-small cell lung cancer will be eligible. do not include patients with conditions that do not allow mri, prior cardiovascular disease with lvef<50%, cardiomyopathy, history of cardiac arrhythmia, history of cardiovascular toxicity under anticancer therapy, coronary artery disease or stroke less than 3 months therapeutic management will not be modified and treatment will be administrated as usual.

cardiovascular follow up will be identical to that recommended and realized in current care in the cardio-oncology unit of ap-hm. it will include clinical, biological (bnp and troponin) and trans-thoracic echocardiography (tte) at baseline and then at 1, 3 and 6 months. auto-antibodies against troponin i assay will be performed to avoid false negatives of normal blood level of troponin i at baseline and then at 6 months. cardiac mri will be performed as well at baseline and at the end of the study (6 months). mri is the gold standard for ventricular function evaluation.

primary endpoint will be left ventricular function evolution evaluated by global longitudinal strain (gls, 2d speckles tracking) in tte. secondary endpoints will be left and right ventricular function parameters: levf by tte and mri, left ventricular indexed volumes by tte and mri, right ejection ventricular function and indexed volumes by tte and mri, systolic pulmonary arterial pressure by tte, serum troponin i and bnp, arrhythmias and conduction disorders on the electrocardiogram (ecg).

number of required subjects: gls is recommended for following up left ventricular function under anticancer treatments. based on the hypothesis of a significant gls decrease (15%) in 20% of cases with alpha risk of 0.05 and accuracy of 0.12 which means expected confidence interval of 0.08-0.32, then the number of required subjects is 50 patients.

the inclusion period will be 18 months with a follow up if 6 months, ie a total duration of the study of 24 months.","inclusion criteria:

patients treated with nivolumab

exclusion criteria:

age <18 years
preliminary cardiac disease with fevg <50%
cardiomyopathy dilated, hypertrophic or restrictive
history of cardiac arrhythmia
history of cardiac toxicity under another anti-cancer treatment
known coronary disease
history of stroke less than 3 months old
patient not wishing to participate in the study
vulnerable persons (pregnant women, adults under guardianship or guardianship, persons deprived of their liberty)",1,0,0,0,1,0,18.0,200.0,Pleura,Pleura,0,1,All
126,126,126,781,NCT03319628,2023-01-23,first-in-human study of xmt-1536 in cancers likely to express napi2b,"a phase 1b/2, first-in-human, dose escalation and expansion study of xmt-1536 in patients with solid tumors likely to express napi2b",,interventional,"first-in-human, phase 1b/2 safety study of the antibody-drug conjugate (adc) xmt-1536 (upifitamab rilsodotin) administered as an intravenous infusion once every four weeks. patients with tumor types likely to express napi2b were enrolled in dose escalation. patients with platinum-resistant ovarian cancer and non-small cell lung cancer (adenocarcinoma subtype) were enrolled in the expansion segment of this study. patients with platinum-resistant, high-grade serous ovarian cancer are being enrolled in the uplift segment of this study. in addition to safety assessments, the pharmacokinetics of the drug will be assessed along with adc activity. a qtc sub-study has been added for the uplift cohort for a sub-set of sites.","general inclusion criteria (for dose escalation, expansion, and uplift):

ecog performance status 0 or 1
measurable disease as per recist, version 1.1
resolution of all acute toxic effects of prior therapy or surgical procedures to ≤grade 1 (except alopecia, stable immune-related toxicity such as hypothyroidism on hormone replacement, adrenal insufficiency on ≤10 mg daily prednisone [or equivalent], chronic grade 2 peripheral sensory neuropathy after prior taxane therapy).
cardiac left ventricular ejection fraction (lvef) ≥50% or ≥ the institution's lower limit of normal by either echo or muga scan

adequate organ function as defined by the following criteria:

absolute neutrophil count (anc) ≥1500 cells/mm3
platelet count ≥100,000/mm3
hemoglobin ≥9 g/dl
in patients not on anticoagulation therapy: inr, activated partial thromboplastin time (aptt), and prothrombin time (pt) all within 1.2 times the institution's upper limit of normal (uln). patients on anticoagulation therapy are allowed if their relevant laboratory values are within the therapeutic window.
estimated glomerular filtration rate (gfr) ≥45 ml/min
total bilirubin ≤uln
g. patients with asymptomatic elevations in unconjugated bilirubin due to gilbert syndrome or stable chronic hemolytic anemia (e.g., hereditary spherocytosis, sickle cell disease, thalassemia intermedia) may be eligible after discussion with the sponsor medical monitor.
aspartate aminotransferase (ast or sgot) and alanine aminotransferase (alt or sgpt) ≤1.5 times the institutional uln.
albumin ≥3.0 g/dl
able to provide informed consent.

general exclusion criteria (for dose escalation, expansion, and uplift) :

major surgery within 28 days of starting study treatment, systemic anti-cancer therapy within the lesser of 28 days or 5 half-lives of the prior therapy before starting study treatment, or recent radiation therapy with unresolved toxicity or within a time window of potential toxicity.
patients with untreated cns metastases (including new and progressive brain metastases), history of leptomeningeal metastasis or carcinomatous meningitis.
current known active infection with hiv, hepatitis b virus, or hepatitis c virus.
prior history of liver disease such as liver cirrhosis, hepatic fibrosis
current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease) or intercurrent illness that could interfere with per-protocol evaluations.
current use of either constant or intermittent supplementary oxygen therapy.
history of suspected pneumonitis or interstitial lung disease.
pregnant or nursing women.
history of other malignancy within the last 2 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or other malignancy with a similar expected curative outcome.
active corneal disease, or history of corneal disease within 12 months prior to enrollment
use of strong cyp450 3a inhibitors or inducers that cannot be discontinued while receiving study treatment
oxygen saturation on room air <93%

ovarian cancer inclusion criteria for uplift:

histological diagnosis of high grade serous ovarian cancer, which includes fallopian tube, or primary peritoneal cancer, that is metastatic or recurrent.

platinum-resistant disease

patients who have only had 1 line of platinum-based therapy must have received at least 4 cycles of platinum, must have had a response [complete response/remission (cr) or partial response/remission (pr)], and then progressed between 3 months and ≤ 6 months after the date of the last dose of platinum
patients who have received 2 to 4 lines of prior therapy must have received at least 4 cycles of platinum and then progressed within 6 months after the date of the last dose of platinum

one to 4 prior lines of systemic therapy for ovarian cancer

a. prior treatment with bevacizumab is required for patients with 1 to 2 prior lines of therapy

patients must be willing to provide an archival tumor tissue block or slides or if not available, undergo procedure to obtain a new tumor biopsy using a low-risk, medically routine procedure

ovarian cancer exclusion criteria for uplift:

low-grade, clear cell, endometrioid, mucinous, carcinosarcoma, germ-cell, mixed histology, or stromal tumors
prior treatment with mirvetuximab soravtansine or another adc containing an antitubulin payload
primary platinum-resistant disease, defined by a lack of response or by progression within 3 months after completing front-line, platinum-containing therapy.
participation in des or exp segments of this study

ovarian cancer inclusion criteria for qtc sub-study:

note: patients must meet all uplift cohort inclusion criteria in order to participate in the qtc sub-study

• study patient has agreed to remain in the clinic for the additional qtc related study activities on the day 1 of cycle 1 and cycle 3.

ovarian cancer exclusion criteria for qtc sub-study:

use of strong cyp450 3a inducers.
uncontrolled cardiac arrhythmias, for example, atrial fibrillation with a ventricular response at rest > 100 beats per minute. left bundle branch block (lbbb)
known abnormality of any cardiac valve (either stenosis or regurgitation) that is greater than moderate in severity.
subjects not in sinus rhythm at screening with hr >45- <100
any ecg abnormality that can interfere with the measurement of the qt interval",1,1,1,0,0,0,18.0,200.0,Pleura,Pleura,0,0,All
127,127,127,783,NCT03319940,2023-10-24,"study evaluating safety, tolerability and pharmacokinetics (pk) of tarlatamab in adults with small cell lung cancer (sclc)","a phase 1 study evaluating the safety, tolerability and pharmacokinetics of tarlatamab in subjects with small cell lung cancer (dellphi-300)",,interventional,"a study to assess the safety, tolerability, and pk of tarlatamab in participants with sclc","inclusion criteria:

participant has provided informed consent prior to initiation of any study-specific activities/procedures
age greater than or equal to 18 years old at the time of signing the informed consent
histologically or cytologically confirmed sclc. for parts a, c, d, e, f, and g: relapsed/refractory small cell lung cancer (r/r sclc) who progressed or recurred following platinum-based regimen
eastern cooperative oncology group (ecog) performance status of 0-2
participants with treated brain metastases are eligible provided they meet defined criteria
adequate organ function as defined in protocol

exclusion criteria:

history of other malignancy within the past 2 years prior to first dose of tarlatamab with exceptions
major surgery within 28 days of first dose tarlatamab
untreated (includes new lesions or progression in previously treated lesions) or symptomatic brain metastases and leptomeningeal disease (regardless of symptomatic or not).
prior anti-cancer therapy: at least 28 days must have elapsed between any prior anti-cancer therapy and first dose of tarlatamab with the following exceptions: participants who received conventional chemotherapy are eligible if at least 14 days have elapsed and if all treatment-related toxicity has been resolved to grade less than or equal to 1; and prior palliative radiotherapy must have been completed at least 7 days before the first dose of tarlatamab
participants who experienced severe, life-threatening or recurrent (grade 2 or higher) immune-mediated aes or infusion-related reactions including those that lead to permanent discontinuation while on treatment with immune-oncology agents
has evidence of interstitial lung disease or active, non-infectious pneumonitis
has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of tarlatamab
part c only: history of solid organ transplantation or active autoimmune disease that has required systemic treatment within the past 2 years
participant with symptoms and/or clinical signs and/or radiographic signs that indicate an acute and/or uncontrolled active systemic infection within 7 days prior to the first dose of investigational product administration",1,1,0,0,0,0,18.0,200.0,Lung,Lung,0,0,All
128,128,128,785,NCT03328078,2023-09-11,a study of ca-4948 in patients with relapsed or refractory primary central nervous system lymphoma,"an open-label, dose escalation and dose expansion trial evaluating the safety, pharmacokinetics, pharmacodynamics, and clinical activity of orally administered ca-4948 in patients with relapsed or refractory primary central nervous system lymphoma",,interventional,"this is a multi-center, open-label trial to evaluate the safety, pharmacokinetics (pk), and anti-cancer activity of oral administration of emavusertib (ca-4948) in adult patients with relapsed or refractory (r/r) hematologic malignancies. part a will evaluate the safety and tolerability of escalating doses of emavusertib as monotherapy (part a1), and in combination with ibrutinib. in protocol version (v) 1.0 through v6.0, patients with waldenström macroglobulinemia/ lymphoplasmacytic lymphoma (wm/lpl) and chronic lymphocytic leukemia (cll)/small lymphocytic lymphoma (sll) were also enrolled at ibrutinib doses of 420 mg (part a2). enrollment into parts a1 and a2 has been closed. part b will comprise 2 cohorts to assess safety and efficacy of emavusertib in combination with ibrutinib in patients with primary central nervous system lymphoma (pcnsl).","inclusion criteria:

males and females greater than or equal to 18 years of age
life expectancy of at least 3 months
eastern cooperative oncology group (ecog) performance status of 0, 1 or 2

histopathologically confirmed diagnosis of pcnsl (medical record is acceptable). cerebral biopsies are not required if imaging reveals typical images of pcnsl.

patients with parenchymal lesions must have unequivocal evidence (e.g., presence of at least 1 bi-dimensionally measurable target lesion on brain magnetic resonance imaging (mri) or head ct or a new lesion with csf involvement) of disease progression on imaging within 28 days prior to cycle 1 day 1.
for patients with leptomeningeal disease only, csf cytology must document lymphoma cells or monotypic cells on flowcytometry, and/or imaging findings consistent with csf disease within 28 days prior to cycle 1 day 1 (at the discretion of the investigator).

exclusion criteria for part b - pcnsl expansion cohorts of combination therapy

patients with only intraocular pcnsl without brain lesion or csf involvement or t-cell lymphoma or systemic presence of lymphoma, or non-cns lymphoma metastatic to the cns
prior history of malignancies other than lymphoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) or prior history of systemic lymphoma, unless the patient has been free of the disease for ≥ 3 years.
active malignancy other than pcnsl requiring systemic therapy
history of grade ≥ 3 rhabdomyolysis without complete recovery
patient has received external beam radiation therapy to the cns within 28 days prior to cycle 1 day 1.
prior investigational drugs (including treatment in clinical research, unapproved combination products, and new dosage forms) within 28 days or 5 half-lives, whichever is shorter, prior to cycle 1 day 1; allogeneic hematopoietic stem cell transplant (hsct) within 60 days prior to c1d1; or clinically significant graft-versus-host disease (gvhd) requiring ongoing up-titration of immunosuppressive medications prior to screening note: the use of a stable or tapering dose of immunosuppressive therapy post-hsct and/or topical steroids for ongoing skin gvhd is permitted with sponsor medical monitor approval
any prior systemic anti-cancer treatment such as chemotherapy, immunomodulatory drug therapy, etc., received within 14 days or 5 half-lives, whichever is shorter, prior to cycle 1 day 1 (with the exception of ibrutinib, which may be continued as part of this study without interruption)
prior history of hypersensitivity or anaphylaxis to emavusertib or ibrutinib or any excipients.",1,1,1,0,0,0,18.0,200.0,Pleura,Pleura,0,0,All
129,129,129,788,NCT03333356,2022-10-24,adjuvant radiotherapy in patients with pathological high-risk bladder cancer (getug-afu 30),adjuvant radiotherapy in patients with pathological high-risk bladder cancer: a randomized multicentre phase ii study,Bladder-ART,interventional,"this is a randomized multicentre study in patients with high-risk mibc to investigate adjuvant radiotherapy after radical cystectomy and pelvic lymph node dissection.

the objective of the study is to provide evidence that adjuvant radiotherapy improves loco-regional control with potential benefits in survival. the study will also evaluate the quality of life of patients and the tolerance of the treatment.","inclusion criteria:

to be eligible, the patients must fulfil all of the following inclusion criteria:

patients with histologically-confirmed muscle-invasive bladder cancer, either with pure urothelial carcinomas, or dominant urothelial carcinomas (>50%) combined with other histological variants including: micropapillary, epidermoid, or adenocarcinomas, are eligible. patients with small cell variants, pure adenocarcinomas, or pure epidermoid carcinomas are not eligible.

patients with radical cystectomy and pelvic lymph nodes dissection with no microscopic residual disease (r0 and r1).

note that only r1 patients without urinary diversion as orthotropic neo-bladder replacement are eligible for the study, to limit cystectomy bed radiation induced toxicities.

patients with tumours of tnm staging: pn0-2, m0 by imagery, and pt3a, pt3b, pt4a, and pt4b, as well as, ptx-pn1-2, ptx-nx-r1 are eligible.
patients having received neo-adjuvant or adjuvant chemotherapy treatment are eligible. randomization is allowed only if ae due to chemotherapy are ≤grade 2 at randomization.
patients ≥18 years old.
eastern cooperative oncology group (ecog) performance status ≤2.
absolute neutrophil count (anc) ≥1500 cells/mm³.
platelets ≥100000 cells/mm³.
haemoglobin ≥8 g/dl (note: following a blood transfusion or another intervention if required).
adequate hepatic function: aspartate aminotransferase (asat) and alanine aminotransferase (alat) ≤2.5 x upper limit of normal (uln); or ≤3.5 x uln in the case of concurrent disease with known etiology and for which a corrective treatment is possible.
adequate renal function: clearance >30 ml/min (mdrd).
patients having provided written informed consent prior to any study-related procedures.
patients affiliated to the social security scheme.
patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol.

exclusion criteria:

patient must not be enrolled if he/she fulfils any of the following non-inclusion criteria:

patients with r1 resection and with orthotropic neo-bladder reconstruction as urinary diversion are not eligible.
patients with clinical or radiological evidence of metastases or n3 staged bladder cancer are not eligible.

prior invasive solid tumours or haematological malignancies unless disease free for a minimum of 3 years prior to randomisation except:

skin basal cell carcinoma,
in situ epithelioma of the cervix,
or prostate cancer: incidentally discovered during cystoprostatectomy and pelvic lymph node dissection and with a good prognosis (t stage <pt3b and/or gleason <8 and pn- and/or post-operative prostate-specific antigen (psa) <0.1 nanogram/ml),
prior pelvic radiotherapy.
patients with active inflammatory bowel disease.
patients who required surgical treatment for bowel obstruction before bladder cancer diagnosis or after cystectomy.
prior chemotherapy for other malignant diseases within the previous 5 years, except for neoadjuvant pre-cystectomy chemotherapy or adjuvant chemotherapy which are permitted.

patients with the following severe acute co-morbidity are not eligible:

unstable angina or congestive heart failure that required hospitalization in the 6 months before randomisation.
transmural myocardial infarction in the 6 months prior to randomisation.
acute bacterial or fungal infection requiring intravenous antibiotics at randomisation.
chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of randomisation.
severe hepatic disease: child-pugh class b or c hepatic disease.
known acquired immune deficiency syndrome (aids); the study treatment could impact blood count.
patients with any other disease or illness which requires hospitalization or is incompatible with the study treatment are not eligible.
patients unable to comply with study obligations for geographic, social, or physical reasons, or who are unable to understand the purpose and procedures of the study.
patients enrolled in another therapeutic study within 30 days prior of randomisation.
person deprived of their liberty or under protective custody or guardianship.",1,0,0,0,0,1,18.0,200.0,Bladder,Bladder,0,0,All
130,130,130,792,NCT03337698,2023-10-13,a study of multiple immunotherapy-based treatment combinations in participants with metastatic non-small cell lung cancer (morpheus- non-small cell lung cancer),"a phase ib/ii, open-label, multicenter, randomized umbrella study evaluating the efficacy and safety of multiple immunotherapy-based treatment combinations in patients with metastatic non-small cell lung cancer (morpheus-lung)",Morpheus Lung,interventional,"this study will evaluate the efficacy, safety, and pharmacokinetics of immunotherapy-based treatment combinations in participants with metastatic non-small cell lung cancer (nsclc).

two cohorts will be enrolled in parallel in this study: cohort 1 will consist of participants with tumor pd-l1 expression who have received no prior systemic therapy for metastatic nsclc, and cohort 2 will consist of participants who experienced disease progression during or following treatment with a platinum-containing regimen and a pd-l1/pd-1 checkpoint inhibitor, given in combination as one line of therapy or as two separate lines of therapy, regardless of pd-l1 expression. in each cohort, eligible participants will initially be assigned to one of several treatment arms (stage 1). participants who experience disease progression, loss of clinical benefit, or unacceptable toxicity during stage 1 may be eligible to continue treatment with a different treatment regimen (stage 2).","general inclusion criteria

eastern cooperative oncology group (ecog) performance status of 0 or 1
life expectancy greater than or equal to 3 months
histologically or cytologically confirmed metastatic, non-squamous or squamous non-small cell lung cancer (nsclc)
measurable disease (at least one target lesion)
adequate hematologic and end-organ function
tumor accessible for biopsy
for women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating eggs as outlined for each specific treatment arm
for men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as outlined for each specific treatment arm

inclusion criteria for cohort 1

no prior systemic therapy for metastatic nsclc
high tumor pd-l1 expression, defined as tumor proportion score (tps) or tcs >= 50% or tc3

inclusion criteria for cohort 2

- disease progression during or following treatment for metastatic or locally advanced, inoperable nsclc

exclusion criteria

prior allogeneic stem cell or solid organ transplantation
uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
symptomatic, untreated, or actively progressing central nervous system (cns) metastases
history of leptomeningeal disease
active or history of autoimmune disease or immune deficiency
history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan
history of malignancy other than nsclc within 2 years prior to screening
active tuberculosis
severe infection within 4 weeks prior to initiation of study treatment",1,1,1,0,0,0,18.0,200.0,Lung,Lung,1,0,All
131,131,131,796,NCT03340506,2023-07-14,dabrafenib and/or trametinib rollover study,"open label, multi-center roll-over study to assess long term safety in patients who have completed a global novartis or gsk sponsored dabrafenib and/or trametinib study",,interventional,"this study is to provide access for patients who are receiving treatment with dabrafenib and/or trametinib in a novartis-sponsored oncology global development, global medical affairs or a former gsk-sponsored study who have fulfilled the requirements for the primary objective, and who are judged by the investigator as benefiting from continued treatment in the parent study as judged by the investigator at the completion of the parent study.","inclusion criteria:

patient is currently receiving treatment with dabrafenib/trametinib monotherapy or combination within a novartis or former gsk sponsored study which has fulfilled the requirements for the primary objective.
in the opinion of the investigator would benefit from continued treatment.

exclusion criteria:

patient has been previously permanently discontinued from study treatment in the parent protocol.
patient's indication is commercially available and reimbursed in the local country.
patient currently has unresolved toxicities for which dabrafenib and/or trametinib dosing has been interrupted in the parent study.",1,0,0,0,1,0,18.0,100.0,Brain,Other,0,0,All
132,132,132,798,NCT03340896,2023-09-21,trial of laryngeal preservation comparing induced ct followed by rt vs ct concomitant to rt,"phase iii trial of laryngeal preservation comparing induction chemotherapy with cisplatin, 5-fluorouracil and docetaxel (tpf) followed by radiotherapy and concomitant administration of radiotherapy with cisplatin",SALTORL,interventional,"this study compare the survival without laryngeal dysfunction 2 years after the end of treatment, obtained by chemotherapy followed by radiotherapy or chemotherapy with cisplatin administrated during radiotherapy.","inclusion criteria:

squamous cell carcinoma of the larynx or hypopharynx, histologically proven, locally advanced:

t2 not accessible to a supra-cricoid partial laryngectomy or not,
t3 without massive infiltration by endolarynx transglottic injury,
n0 to n2c
no distant metastasis
no associated cancer or earlier
patients previously untreated
age> 18 years and <75 years
ps 0 or 1 according to who
tumor volume assessable by recist.
absence of distant metastasis, confirmed by chest tdm, abdominal ultrasound (or tdm) in case of abnormal liver function and bone scan if local symptoms.
absence of any participation in a clinical trial within 30 days prior to inclusion.
absence of any concomitant cancer treatment.
absence of any chronic treatment ( ≥3 months) with a daily corticosteroid dose is ≥20 mg / day of methylprednisolone or equivalent.
hematological function: neutrophils ≥1.5 x 109 / l, platelets ≥100 x 109 / l, hemoglobin ≥10 g / dl (or 6.2 mmol / l).
hepatic function: normal total bilirubin; ast (sgot) and alt (sgpt) ≤ 2.5 x uln (lns) of each center; alkaline phosphatase ≤ 5 x lns.
renal function: serum creatinine ≤ 120 mol / l (1.4 mg / dl); if creatinine > 120 mol / l, creatinine clearance should be ≥ 60 ml / min.
calculated creatinine clearance (crockcroft formula) or measured ≥ 60 ml / min
estimated life expectancy ≥ 3 months
weight loss less than 10% over the last 3 months
patient has given its written consent before any specific procedure of the protocol.
women and men of childbearing age should have accepted a medically effective contraception during the treatment period and at least 6 months after discontinuation of study treatments (docetaxel, 5-fluorouracil and cisplatin. if pregnancy is declared by a patient or partner of a patient, it must be followed to know the evolution of pregnancy.

exclusion criteria:

transglottic t3 with massive infiltration of hemilarynx or t4 with massive cartilaginous tumor lysis or reverse cricoarythénoïdenne region or posterior hypopharyngeal wall
tumor requiring the completion of an immediately tracheotomy.
tumour available immediately to partial surgery.
tumor requiring circular hypopharyngectomie
n3 nodal injury
vaccination against yellow fever recent or anticipated
deficit known dihydropyrimidine dehydrogenase (dpd)
other malignancies within 5 years prior to randomization, with the exception of adequately treated basal skin cancer and carcinoma in situ of the cervix.
patients with ast or alt> 1.5xuln associated with alkaline phosphatase > 2.5x lns will not be eligible for testing.
symptomatic neuropathy grade ≥2 with nci-ctc.
clinical alteration of hearing function.

other concomitant serious medical conditions (partial list):

unstable cardiac disease despite treatment.
myocardial infarction within 6 months prior to trial entry.
neurological or psychiatric history such as dementia, seizures;
severe uncontrolled infection.
significant gastrointestinal abnormalities, including those that require parenteral nutrition, active peptic ulcer disease and a history of surgical procedures affecting absorption
obstructive pulmonary disease requiring hospitalization in the year before inclusion.
unstable diabetes or other cons-indications to corticosteroids.
significant ophthalmologic abnormality.
moderate or severe eczema.
allergy to iodine.
hypersensitivity to docetaxel, cisplatin or at one of their excipients.
concomitant use of phenytoin, carbamazepine, barbiturates and rifampicin.
presence, selection, psychological factors, family, social or geographical may alter patient compliance with the study protocol and follow-up, a criterion of non-inclusion. these factors should be discussed with the patient before inclusion in the trial.
pregnant or nursing women.
patient (male or female) of childbearing age not taking adequate contraceptive measures.
patient deprived of their liberty, without guardianship or curatorship.",1,0,0,1,0,0,18.0,75.0,Lung,Lung,0,0,All
133,133,133,801,NCT03351296,2023-05-16,two chemotherapy regimens plus or minus bevacizumab,randomized phase 2 trial of two chemotherapy regimens plus or minus bevacizumab in patients with well differentiated pancreatic neuroendocrine tumors,BETTER2,interventional,"compare the effect of capecitabine (cape) + temozolomide (temo) and of 5fu + streptozotocin (strepto) given with a new schedule (lv5fu2 + strepto), two of the most used chemotherapy regimens in the treatment of well differentiated pancreatic neuroendocrine tumors alone or in combination with bevacizumab (beva) on progression-free survival (pfs) and compare the chemotherapy regimens alone or with beva (two by two design) on the same criteria.","well differentiated pancreatic neuroendocrine tumor grade 1 (net g1), grade 2 (net g2) or grade 3 (net g3)*

*grade 3 tumor must be confirmed by a pathologist of the tenpath network.

indication for chemotherapy for locally advanced or metastatic disease with proven progression (at least 20% increase of tumor size on a maximum of 12 months period of follow-up) or other indication of chemotherapy following the national thesaurus of gi cancerology (appendix 6) (liver involvement > 50%, symptoms related to the tumour or its metastases, ki67>10%)
patient with at least one measurable target tumor by recist 1.1 and that has never been irradiated
patient with a life expectancy greater than 3 months
men or women with performance status (ecog) ≤ 2 (appendix 3)
age ≥ 18 years
adequate hematological function: neutrophil count (anc) ≥ 1.5x109/l, platelets greater than 75x109/l, hemoglobin greater than 10g/dl (blood transfusions are accepted to reach this level).
adequate liver function: serum bilirubin lower than 3 x upper limit of normal (uln); aminotransferases and alkaline phosphatase levels lower than 2.5 uln (lower than 5 uln if liver metastases), tp greater than 50 %
proteinuria lower than 1g/24h, blood creatinine less than 120 μmol/l and creatinin clearance ≥ 60 ml/min as calculated by cockroft-gault formula note: a negative dipstick urine analysis is sufficient.
absence of active bleeding, coagulopathy or pathologic condition that would confer a high risk of bleeding
prior treatment with somatostatin analogues, everolimus or sunitinib is allowed
negative serum pregnancy test ≤ 72 hours before randomization (for women of childbearing potential only). sexually active women of childbearing potential must agree to use a highly effective method of contraception or to abstain from sexual activity during the study and for at least 6 months after the last study treatment administration. sexually active males patients must agree to use condom during the study and for at least 6 months after the last study treatment administration. also, it is recommended their women of childbearing potential partner use a highly effective method of contraception.
patient should understand, sign, and date the written informed consent form prior to any protocol-specific procedures performed. patient should be able and willing to comply with study visits and procedures as per protocol.
patient affiliated to a social security regimen or beneficiary of such regimen

non inclusion criteria :

disease accessible to resection or percutaneous method of destruction
any known allergy or contraindication to the treatments used in the trial
patients with a complete dpd deficiency; defined as an uracil concentration ≥150ng/ml note: patients with a suspicion of partial dpd deficiency, defined as a uracil concentration ≥ 16 ng/ml and < 150 ng/ml, will receive an adapted 1st cycle dose, according to a clinic-biological discussion. the dose can be then readapted for the second cycle according to the tolerability of the treatment during the 1st cycle.
patient previously treated with chemotherapy for the neuroendocrine tumour
patient have received any other antitumor therapy: chemotherapy, immunotherapy
other serious diseases such as respiratory failure or congestive heart failure, angina pectoris not medically controlled; history of myocardial infarction within 6 months prior to study entry, uncontrolled hypertension and arrhythmias, concomitant severe infection or uncontrolled diabetes mellitus
subjects with a history of chronic or acute hepatitis c or b infection.
surgery during the 5 weeks preceding the randomization
history of cancer (except basal cell skin or carcinoma in situ carcinoma of the cervix) within 5 years prior to entry into the trial. but patients with cancers that have been treated more than 5 years ago and are considered as cured are eligible.
neurological or psychiatric pathology that may interfere with adherence to treatment
patients have received yellow fever vaccine within 30 days prior to the first dose of trial treatment.
patient with pernicious anaemia and other megaloblastic anaemias secondary to the lack of vitamin b12
hypersensitivity to chinese hamster ovary (cho) cell products or other recombinant human or humanised antibodies
hypersensitivity to study drugs or any of its excipients
patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving its consent
pregnant or breast feeding women",1,0,1,0,0,0,18.0,200.0,Pleura,Brain,0,0,All
134,134,134,806,NCT03357120,2017-11-28,circulating tumor dna after neoadjuvant chemotherapy,detection of circulating tumoral dna mutations (sequential assessment) following neoadjuvant chemotherapy for breast cancer: clinical validity (alienor study),ALIENOR,interventional,trial assessing the prognostic value of ctdna mutations from samples taken sequentially in patients with invasive breast cancer initially treated with neoadjuvant chemotherapy and whose tumor is not in complete histological response.,"inclusion criteria :

age ≥ 18 years (no age limit).
women or men.

invasive breast cancer proven histologically at diagnosis (before neoadjuvant chemotherapy):

locally advanced tumor known to be inoperable from the start:

ct4a, b, c, d whatever the cn
or cn2 or cn3 whatever the ct.

operable tumors:

ct2cn1 or ct3cn0 or ct3n1,
or ct2cn0 for which ganglionic invasion has been proven by cytology or histology.
lack of clinically or radiologically detectable metastases in the initial diagnosis before the neoadjuvant chemotherapy (m0).
unilateral or bilateral breast cancer. multifocality is accepted.
patients who received 6 to 8 cycles of neoadjuvant chemotherapy.
preoperative radiation therapy allowed.
breast surgery performed and pathology report of a non-complete histological response (i.e. all the different results of ypt0 /is ypn0).
signed informed consent.
patients affiliated to a french social security scheme in accordance with article 1121-11 of the french code of public health.
possible inclusion in another interventional research (surgical, radiotherapy or drug study).

exclusion criteria :

ct2cn0 tumor without cytological or histological lymph node involvement.
progression during neoadjuvant chemotherapy.
exclusive neoadjuvant hormone therapy.
complete blood transfusion within 120 days prior to 1st sampling.
history of invasive cancer regardless of the time elapsed since the diagnosis of this cancer, including a history of contralateral invasive breast cancer. however, patients who have been treated for in situ breast cancer, basocellular skin cancer or cervical cancer treated in situ are eligible.
patient unable to follow and comply with research procedures for geographical, social or psychological reasons.
patient deprived of liberty or subject to a legal protection measure.",1,0,0,0,0,1,18.0,200.0,Other,Breast,0,0,All
135,135,135,810,NCT03362801,2023-09-04,"sarcopenia, mobility, physical activity and post-operative risk of bladder carcinoma in the elderly","sarcopenia, mobility, physical activity and post-operative risk of bladder carcinoma in the elderly",SAMPHYR,interventional,"sarcopenia is associated with lower prognosis in solid tumors, but this has not been studied in bladder carcinoma requiring cystectomy.

according to ewgsop recommendations, the diagnosis of sarcopenia is based on walking speed, grip strength and muscle mass. these three elements can easily be measured (specially muscle mass measurement by bioimpedencemetry or tomodensitometry).

this cohort study will collect clinical complementary elements to better understand the associated factors present with sarcopenia, in order to prepare an interventional preoperative physical reconditioning study.

the mobility measurement will be carried out by the qappa questionnaire (validated in french in the elderly) and the quantitative measurement of activity and rest hours during a week by a wrist actimeter.

standardized geriatric data will also be collected: adl, iadl for autonomy, mmse for cognitive status, nutritional status (% weight loss, bmi), pain, gds15 for depression screening, updated charlson comorbidity index to identify polypathology and the stopp tool for potentially inappropriate medication.

post-operative morbidity mortality at 30 days will be evaluated according to clavien-dindo classification. investigators will also evaluate 6 months geriatric complications : falls, loss of autonomy and decreased mobility and physical activity, cognitive degradation, undernutrition, institutionalization","inclusion criteria:

confirmed urothelial bladder carcinoma ( rtuv)

indication of radical cystectomy
able, informed and with informed consent for the study
affiliated to the social security system
talking french

exclusion criteria:

life expectancy <6 months

other active malignant tumors or other severe concomitant chronic pathologies affecting the general condition of the patient and / or likely to limit compliance with the requirements of the study.
treatments incompatible with the study: previous corticosteroid treatment prolonged for more than one month (induces iatrogenic sarcopenia).",1,0,0,0,0,1,65.0,200.0,Bladder,Bladder,1,0,All
136,136,136,811,NCT03363373,2023-03-06,naxitamab for high-risk neuroblastoma patients with primary refractory disease or incomplete response to salvage treatment in bone and/or bone marrow,a pivotal phase 2 trial of antibody naxitamab (hu3f8) and granulocyte-macrophage colony stimulating factor (gm-csf) in high-risk neuroblastoma patients with primary refractory disease or incomplete response to salvage treatment in bone and/or bone marrow,,interventional,"children and adults diagnosed with high-risk neuroblastoma patients with primary refractory disease or incomplete response to salvage treatment in bone and/or bone marrow will be treated for up to 101 weeks with naxitamab and granulocyte-macrophage colony stimulating factor (gm-csf). patients will be followed for up to five years after first dose.

naxitamab, also known as hu3f8 is a humanised monoclonal antibody targeting gd2","inclusion criteria:

diagnosis of neuroblastoma as defined per international neuroblastoma response criteria
high-risk neuroblastoma patients with either primary refractory disease or incomplete response to salvage treatment (in both cases including stable disease, minor response and partial response) evaluable in bone and/or bone marrow.
life expectancy ≥ 6 months

exclusion criteria:

any systemic anti-cancer therapy, including chemotherapy or immunotherapy, within 3 weeks before 1st dose of gm-csf
evaluable neuroblastoma outside bone and bone marrow
existing major organ dysfunction > grade 2, with the exception of hearing loss, hematological status, kidney and liver function
active life-threatening infection",1,0,1,0,0,0,1.0,200.0,Brain,Brain,1,0,All
137,137,137,812,NCT03364530,2023-05-02,hepatic arterial infusion of gemcitabine-oxaliplatin for second-line therapy in non-metastatic unresectable intra-hepatic cholangiocarcinoma,hepatic arterial infusion of gemcitabine-oxaliplatin for second-line therapy in non-metastatic unresectable intra-hepatic cholangiocarcinoma: a multicentric single-arm phase ii study,GEMOXIA-02,interventional,we hypothesized that intra-arterial gemcitabine/oxaliplatin administered as second-line treatment could strongly improve objective response rate at 4 months after inclusion in patient with non-metastatic unresectable intra-hepatic cholangiocarcinoma.,"inclusion criteria:

histologically-proven intrahepatic cholangiocarcinoma previously treated by first-line systemic therapy
absence of extra-hepatic metastasis or peritoneal carcinomatosis (as demonstrated by ct-scan)
general health status : world health organization performance status = 0, 1
estimated life expectancy > 3 months
disease that is not suitable for resection with a curative intent, as validated by a multidisciplinary committee with at least one senior hepatic surgeon
at least one measurable lesion according to recist 1.1 criteria
platelets ≥100,000/mm3, polynuclear neutrophils ≥ 2000/mm3 , hemoglobin 9g/dl (even transfused patients can be included)
creatininemia < 1.5 mol/l
creatinine clearance > 30 ml/min
bilirubinemia ≤2 n (after biliary drainage if necessary)
aspartate and alanine transaminase ≤ 5 mol/l
reference hepatic mri (according to the foreseen protocol) done during the 30 days preceding the 1st cycle of treatment
written informed consent
national health insurance cover

exclusion criteria:

patients with cholangiocarcinoma of the gallbladder or common bile duct or those with hepatocholangiocarcinoma or a klatskin tumor
patients who are eligible for surgical resection or liver transplantation
extra-hepatic metastases (pulmonary micronodules <7mm without uptake on positron emission tomography are not a contra-indication)
presence of clinical ascites
history of intra-arterial therapy or more than one line of systemic treatment
contra-indication or grade 3-4 allergy to any of the treatment drugs gemcitabine, oxaliplatin (notably myelosuppression developped before the beginning of the first cycle of therapy, peripheral sensory neuropathy before the first cycle of therapy, severe renal failure)
grade 2 peripheral neuropathy
ongoing participation or participation within the 21 days prior to inclusion in the study in another therapeutic trial with an experimental drug
concomitant systemic treatment with immunotherapy, chemotherapy or hormone therapy
serious non-stabilized disease, active uncontrolled infection or other serious underlying disorder likely to prevent the patient from receiving the treatment
pregnancy (beta-human chorionic gonadotropin positive), breast-feeding or the absence of effective contraception for women of child-bearing age
another cancer in the 5 years preceding or at the time of inclusion in the trial (except for in situ cervical cancer or basal cell carcinoma of the skin)
allergy or contra-indication to iodine contrast agents (thyrotoxicosis, allergy to the active substance or excipients)
treatment with anticoagulants (heparin or avk) that cannot be interrupted for 12 hours
treatment with anti-platelets that cannot be interrupted for 5 days for aspirin or plavix.
contra-indication for use of an intra-arterial approach (severe arteriopathy)
legal incapacity (persons in custody or under guardianship)
deprived of liberty subject (by judicial or administrative decision)
impossibility to sign the informed consent document or to adhere to the medical follow-up of the trial for geographical, social or psychological reasons
contraindication for the mri : pacemaker or neurosensorial stimulator or implantable defibrillator, cochlear implant, ferromagnetic foreign body similar to the nervous structure.",1,0,1,0,0,0,18.0,200.0,Pleura,Vulva,0,1,All
138,138,138,816,NCT03374839,2022-05-05,combined therapy of nivolumab and adoptive t cell therapy in metastatic melanoma patients,combined therapy of nivolumab and adoptive t cell therapy in metastatic melanoma patients: pilot study phase i/ii,Nivo-TIL,interventional,"to improve the efficacy of immunotherapy for cancer, recent studies focused on specific targets to redirect the immune network toward eradicating a variety of tumors and ameliorating the self-destructive process.

a clinically relevant immune escape mechanism in melanoma is the activation of the programmed cell death-1 (pd-1) receptor on infiltrating t cells. by blocking pd-1 receptors with anti-pd-1 monoclonal antibodies (mabs), t-cells are unaffected by the pd-l1 expressed on tumor cells and the patients t cells are free to respond to melanoma antigens and attack tumor cells. so the objective of this trial is to evaluate the safety and the efficacy of a combined therapy nivolumab and adoptive t cell therapy in metastatic melanoma patients.","inclusion criteria:

over 18 years old with a weight ≥ 40 kg
patients must have signed informed consent
patients with stage iiib, iiic or iv metastatic melanoma (ajcc 6th edition) with at least two lesions (lymph nodes relapse, or in transit metastasis, or unresectable cutaneous metastases, or visceral metastases except bone and brain metastases) including one easily accessible and no more than 2 lines of treatment of melanoma at the metastatic stage.
patients with a melanoma expressing a braf v600 mutation can be included
measurable/assessable disease in 28 days which precede the first administration of the treatment
a negative pregnancy test for women with childbearing potential
eastern cooperative oncology group (ecog) of 0-1, karnofsky > 80%
laboratory results:

haemoglobin ≥ 10 g/dl or ≥ 6,25 mmol/l; neutrophils ≥ 1500/μl; leukocytes ≥ 4000/μl; lymphocytes ≥ 700/μl; blood platelet ≥ 100.000/μl; serum creatinine ≤ 1.5 x superior normal value or creatinine clearance (crcl) ≥ 40 ml/min (if using the cockcroft-gault formula); serum bilirubin ≤ 2.0 mg/dl or ≤ 34.2 mol/l; total bilirubin ≤ 1.5 x superior normal value (except subjects with gilbert syndrome, who can have total bilirubin < 3mg/dl); aspartate aminotransferase (ast) and alanine aminotransferase (alt) ≤ 2 x superior normal value; lactate dehydrogenase (ldh) ≤ 1.5 x superior normal value

subjects affiliated to an appropriate health insurance
women of childbearing potential (wocbp) must use appropriate method(s) of contraception during the clinical trial. furthermore wocbp will be instructed to adhere to contraception for a period of 5 months after the last dose of nivolumab.
men who are sexually active with wocbp will be instructed to adhere to contraception during the clinical trial and for a period of 7 months after the last dose of nivolumab.
women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile) as well as azoospermic men do not require contraception.

non inclusion criteria:

brain or bone metastases
ocular melanoma
chemotherapy or radiotherapy within 4 weeks before baseline (6 weeks for nitroso-ureas and mitomycin c)
contraindication for the use of vasopressor agents
for female: the patient is pregnant or breastfeeding or not using contraception
for men: the patient is sexually active with wocbp and not using contraception
history or current manifestations of severe progressive heart disease (congestive heart failure, coronary artery disease, uncontrolled arterial hypertension, serious rhythm disorders or ecg signs of previous myocardial infarction)
patients should be excluded if they have had prior treatment with an anti-pd-1, anti-pd-l1, anti-pd-l2, anti-ctla4 antibody, or any other antibody or drug specifically targeting t-cell costimulation or immune checkpoint pathways except in the context of adjuvant or neoadjuvant

history of allergies and adverse drug reaction:

hypersensitivity to human albumin, til excipient
hypersensitivity to nivolumab or related excipients
history of severe hypersensitivity reaction to any monoclonal antibody
hypersensitivity to aldesleukin or to one of proleukin excipients
history of chronic autoimmune disease (addison's disease, multiple sclerosis, graves' disease, rheumatoid arthritis, systemic lupus erythematosus, etc…) except patient with active vitiligo or a history of vitiligo.
history of uveitis or melanoma-associated retinopathy
history of inflammatory bowel disease, celiac disease, or other chronic gastrointestinal conditions associated with diarrhea.
presence of a second active cancer, with the exception of an in situ cervical cancer or a skin cancer different from the treated melanoma
unchecked thyroid dysfunction
any serious, acute or chronic illness id est active infection asking for antibiotics administration, coagulation's disorders, or any state asking for an unauthorized concomitant treatment described in this study
patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days before study drug administration. inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. subjects are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). physiologic replacement doses of systemic corticosteroids are permitted, even if > 10 mg/day prednisone equivalents. a brief course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of nonautoimmune conditions (eg, delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
adults under a legal protection regime (guardianship, trusteeship, ""sauvegarde de justice"")

exclusion criteria:

* positive viral serology for hiv (human immunodeficiency virus) 1/2, p24 ag, htlv1, htlv2, b and c hepatitis or syphilis",1,1,1,0,0,0,18.0,75.0,Pleura,Pleura,0,0,All
139,139,139,825,NCT03386734,2022-07-27,international validation study of sentinel node biopsy in early cervical cancer,international validation study of sentinel node biopsy in early cervical cancer,SENTICOLIII,interventional,"senticol iii is large prospective multicenter international randomized study designed to validate the sentinel lymph node (sln) mapping technique in early cervical cancer. this ""validation study"" will compare the outcome of patients with negative sln (experimental arm) vs patients with negative sln + pelvic lymph node dissection (pln)(reference arm).

there will be a ""quality assurance"" program which will be developed in participating centers with detailed requirements in terms of surgeons' qualifications, pathology qualification, sln ultrastaging, standardization of the procedure, etc. as well as respect of the ""safety algorithm"".","inclusion criteria:

i 1. patient must be ≥ 18 years old, i 2. with squamous or adenocarcinoma or adenosquamous carcinoma of the cervix (proven by biopsy or cone biopsy), i 3. stage ia1 with lymphovascular emboli, ia2, ib1 iia1, ib2 (clinical stage) of the 2018 figo classification (see appendix 1), i 4. maximum diameter ≤ 40 mm by clinical examination and/or magnetic resonance imaging (mri), i 5. no suspicious node on pelvic mri with an exploration up to the left renal vein (according to recist 1.1), i 6. ecog performance status 0-2 (see appendix 2), i 7. signed informed consent and ability to comply with follow-up, i 8. french subjects: in france, a subject will be eligible for inclusion in this study only if either affiliated to, or a beneficiary of, a social security category.

exclusion criteria:

e 1. pregnancy, e 2. previous pelvic or abdominal cancer, e 3. previous chemotherapy and/or radiation therapy for the cervical cancer (previous brachytherapy is accepted), e 4. proven allergy to blue dye, isotope or indocyanine green (icg) e 5. other malignancy within the last 5 years except for treated cancer free of disease and treatment, e 6. patients with synchronous cancer",1,0,0,0,0,1,18.0,200.0,Pleura,Pleura,0,1,Female
140,140,140,827,NCT03389997,2023-02-17,assessement of viral shedding duration after a respiratory tract infection in oncology and hematology patients,assessement of viral shedding duration after a respiratory tract infection in oncology and hematology patients,ONCOVIR,interventional,the purpose of this study is to assess the duration of the viral shedding in hematology and oncology patients after a respiratory tract viral infection. this duration has not been much studied in that population whereas it is probably longer than that in immunocompetent patients. thereby it may be a source of transmission amongst these immunocompromised patients.,"inclusion criteria:

patient with solid organ cancer or haematological malignancy with or without chemotherapy
having symptoms of upper and/or lower respiratory tract infection
virus detected by pcr in nasal sample
signature of consent

exclusion criteria:

hematological stem cell and solid organ recipients
no health insurance
protected people",1,0,0,0,0,1,18.0,200.0,Pleura,Pleura,0,0,All
141,141,141,831,NCT03400072,2018-11-16,adapted physical activity in patients with resected pancreatic cancer (apacapop prodige-56 study): a national multicenter randomized controlled phase ii trial,adapted physical activity in patients with resected pancreatic cancer (apacapop prodige-56 study): a national multicenter randomized controlled phase ii trial,APACaPOp,interventional,"exercise during chemotherapy (ct) is a promising strategy to reduce fatigue and improve health-related quality of life (hrqol). exercise may also have beneficial effects on tumor outcome by decreasing insulin resistance, inflammation, and by modulating various pro-tumoral signalling pathways. it has been shown to reduce mortality in breast and colorectal cancer adjuvant setting.

this study aims to explore the effects of adapted physical activity (apa) in patients with resected pancreatic ductal adenocarcinoma (pdac).","inclusion criteria:

histologically proven pdac
complete macroscopic resection (r0 or r1 resection)
patients randomized within 12 weeks of surgery
no evidence of malignant ascites, liver metastasis, spread to other distant abdominal organs, peritoneal metastasis, spread to extra-abdominal organs
sufficient recovery from the operation and fit to take part in the trial
able to attend for administration of the adjuvant ct
ecog ps 0-2
age ≥ 18 years
life expectancy > 3 months
dated and signed informed consent
registration in a national health care system (cmu included).

exclusion criteria:

macroscopically remaining tumor (r2 resection or tnm stage iv disease)
histology other than pdac
cardiovascular, respiratory, psychiatric, musculoskeletal, or neurological condition contra-indicating exercise practice
pregnancy or breastfeeding
protected adults (individuals under guardianship by court order). note: participation to another concomitant clinical trial is allowed but the patient must inform and get an authorization from the investigator.",1,0,0,0,0,1,18.0,200.0,Pleura,Pleura,0,1,All
142,142,142,832,NCT03400332,2023-10-16,a study of bms-986253 in combination with nivolumab or nivolumab plus ipilimumab in advanced cancers,a phase 1/2 study of bms-986253 in combination with nivolumab or nivolumab plus ipilimumab in advanced cancers,,interventional,the purpose of this study is to investigate experimental medication bms-986253 in combination with nivolumab or nivolumab plus ipilimumab in participants with advanced cancers.,"inclusion criteria:

histologic or cytologic confirmation of a solid tumor that is advanced (metastatic, recurrent and/or unresectable) with measurable disease per recist v1.1
at least 1 lesion accessible for biopsy
eastern cooperative oncology group performance status of 0 or 1

exclusion criteria:

participants with cns metastases as the only site of active disease (participants with controlled brain metastases; however, will be allowed to enroll)
participants with active, known or suspected autoimmune disease
participants with conditions requiring systemic treatment with either corticosteroids (> 10mg prednisone equivalents) or other immunosuppressive medications within 14 days of study treatment administration
participants with a known history of testing positive for human immunodeficiency virus (hiv) or known acquired immunodeficiency syndrome (aids)
cytotoxic agents, unless at least 4 weeks have elapsed from last dose of prior anti-cancer therapy and initiation of study therapy

other protocol defined inclusion/exclusion criteria could apply",1,1,1,0,0,0,18.0,200.0,Brain,Brain,0,0,All
143,143,143,836,NCT03406247,2023-05-17,adjuvant immunotherapy after salvage surgery in head and neck squamous cell carcinoma,"adjuvant immunotherapy after salvage surgery in head and neck squamous cell carcinoma : phase 2 trial evaluating the efficacy and the toxicity of nivolumab alone, and of the combination nivolumab and ipilimumab",ADJORL1,interventional,"two randomized trials of reirradiation after salvage surgery have been conducted by the gettec and gortec collaborative groups, both members of the french hn intergroup: the first trial compared reirradiation and a ""wait and see attitude"" and was published in 2008 [1]. the second trial compared two modalities of reirradiation. our hypothesis is that adjuvant treatment with immunotherapy will lead to a dfs similar to that observed in previous trials of post-operative reirradiation with possibly lower toxicity.","inclusion criteria:

recurrence or second primary of hnscc in a previously irradiated area at a dose ≥ 50 gys
hnscc of oral cavity, oro and hypopharynx, larynx only if extralaryngeal spread (rt4), isolated nodal recurrence
patient who has received salvage surgery with curative intent and macroscopic complete resection:
for cohorts 1 and 2: similarly to inclusion criteria of previous reirradiation trials, more than 6 months between radiotherapy and salvage surgery
for cohorts 1bis and 2bis: less than 6 months between radiotherapy and salvage surgery
recurrence of bad prognosis justifying an adjuvant treatment:
clinically infiltrative recurrence or second primary; or nodal recurrence upper or equal to 3 cm, or association of local and nodal recurrence;
superficial recurrence, but histologic gravity signs on surgical specimen indicating a high risk of recurrence after salvage surgery (histologic involvement of surgical margins or margins less than 3mm, perineural spread or vascular emboli, multiples invaded nodes). nodal recurrence without tumor recurrence and inferior to 3cm, but with capsular rupture at histologic examination.
sufficient healing for beginning adjuvant treatment within 8 weeks (+/- 2 weeks) of salvage surgery
no distant metastases, confirmed by ct or pet scan
male and female between 18 and 75 years (included)
ecog 0 or 1
immunosuppressive doses of systemic medication, such as steroids or absorbed topical steroids (doses > 10 mg/day prednisone or equivalent) must be discontinued at least 2 weeks before study drug administration

screening laboratory values must meet the following criteria (using ctcae v4) and should be obtained within 14 days to the administration of the first study treatment.: wbc > 2,000/μl. polynuclear neutrophils >1.5 x 10^9/l. platelets > 75 x 10^9/l. hemoglobin > 8.0 g/dl. alat/asat< 3.0 x uln. bilirubin < 1.5 x uln (except gilbert syndrome

: < 3.0 mg/dl). creatinine clearance > 40 ml/min (measured or calculated by cockroft and gault formula) or serum creatinine < 2.0 x uln

women of childbearing potential must have a negative serum β-hcg pregnancy test within 24 hours prior to the administration of the first study treatment.
sexually active women of childbearing potential must agree to use a highly effective method of contraception or to abstain from sexual activity during the study and for at least 5 months after the last study treatment administration. sexually active males patients must agree to use condom during the study and for at least 7 months after the last study treatment administration. also, it is recommended their women of childbearing potential partner use a highly effective method of contraception.
women who are breastfeeding should discontinue nursing prior to the first dose of study drug and until 5 months after the last dose.
patient should understand, sign, and date the written informed consent form prior to any protocol-specific procedures performed. patient should be able and willing to comply with study visits and procedures as per protocol.
patients must be affiliated to a social security system or beneficiary of the same

exclusion criteria:

recurrent or metastatic carcinoma of the nasopharynx, squamous cell carcinoma that originated from the skin and salivary gland, or nonsquamous histologies (eg, mucosal melanoma).
recurrence or second primary of hnscc in a non previously irradiated area, or at a dose < 50 gys
macroscopic incomplete surgery (no debulking allowed)
superficial recurrence without nodal recurrence, and without histologic gravity signs (histologic involvement of surgical margins, perineural spread)
nodal recurrence less than 3 cm, without local recurrence and without capsular rupture at histologic examination
serious medical adverse conditions, such as severe cardiac and/or pneumologic and/or liver dysfunction. non exhaustive list, to be appreciated in each center
subjects with active, known or suspected autoimmune disease. subjects with vitiligo, type i diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
patients with positive tests for hepatitis b virus surface antigen (hbv sag) or hepatitis c virus ribonucleic acid (hcv rna) indicating active or chronic infection.
patients with positive test for human immunodeficiency virus (hiv) or known acquired immunodeficiency syndrome (aids).
prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
patients having received prior therapy with anti-pd-1, anti-pd-l1, anti-pd-l2, anti-cd137, or anti-ctla-4 antibody (or any other antibody or drug specifically targeting t-cell co-stimulation or checkpoint pathways).
patients receiving anti-cancer therapies must be discontinued at least 4 weeks prior to administration of study drug. palliative, focal radiation therapy, and immunosuppressive doses of systemic corticosteroids, except replacement organotherapy (hydrocortisone and fludrocortisone), must be discontinued at least 2 weeks before administration of study drug. all toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have resolved to grade 1 (nci ctcae version 4) or to baseline or stabilized before administration of study drug. subjects with toxicities attributed to systemic prior anticancer therapy which are not expected to resolve and result in long lasting sequelae, such as neuropathy after platinum based therapy, are permitted to enroll.
use of non-oncology vaccines containing live virus for prevention of infectious diseases within 4 weeks prior to study drug. the use of the inactivated seasonal influenza vaccine (fluzone®) is allowed.known or underlying medical condition (e.g., a condition associated with diarrhea or acute diverticulitis) that, in the investigator's opinion, would make the administration of study drug hazardous to the patient or obscure the interpretation of toxicity determination or adverse events.
patients requiring concomitant treatment with therapeutic doses of anticoagulants will not be eligible for this clinical trial. patients treated with low dose of anticoagulants for thrombo-embolic events prophylaxis are allowed.
history of auto immune, immune mediated inflammatory disease including but not limited to colitis, pneumonitis, hepatitis, nephritis, inflammatory of skin, snc, eyes, glands producing hormones
active serious infections in particular if requiring systemic antibiotic or antimicrobial therapy
history of severe hypersensitivity reaction to any monoclonal antibody
history of allergy to study drugs components
treatment with other investigational drugs or treatment in another clinical trial within the past 4 weeks before start of therapy or concomitantly with the trial
pregnancy or breastfeeding
psychological, familial or social factor incompatible with informed consent, and regular follow-up.
previous allogenic stem cell transplant or patients recipient of solid organ transplant",1,0,1,0,0,0,18.0,200.0,Pleura,Pleura,0,0,All
144,144,144,838,NCT03408665,2023-02-07,stereotactic body radiation therapy (sbrt) efficiency and toxicity in liver cancer,"phase ii study, stratified, non-randomized, estimating sbrt efficiency and toxicity in primary and secondary liver tumors",STEREOLIVER,interventional,"intervention research involving the human person, phase ii, prospective, multicentric, non-randomized and multi-cohort study. the eligibility criteria are broad, on purpose, so every patient, able to be treated by sbrt and unable to participate in another trial (non eligible patient or non included centers), can be included in this national study, in a prospective way.","inclusion criteria:

age ≥ 18 years old
with primary or secondary liver tumor and matching one of the following situations:
liver metastasis (lm): anatomopathologic diagnosis of the primary tumor
hepatocellular carcinoma (hcc): diagnosis achieved through biopsy or through non-invasive methods approved by aasld criteria (bruix, 2011)
cholangiocarcinoma (cc): diagnosis achieved through biopsy
other primitive hepatic tumor achieved through biopsy
meet the requirements for sbrt treatment:
liver metastasis (lm): oligometastatic disease
hepatocellular carcinoma (hcc): non eligible lesion to curative surgery
cholangiocarcinoma (cc): nodular lesion
other primitive hepatic tumor: non eligible lesion to curative surgery
able to receive a sbrt treatment according to the multidisciplinary consultation meeting
tumor assessable with ct-scan or mri according to mrecist in hcc or recist 1.1 in other situations
affiliation to the national social security system
with informed and signed consent

exclusion criteria:

eligibility to a curative surgery according to the multidisciplinary consultation meeting
contraindication to sbrt (especially cirrhose child c)
pregnant or breastfeeding women
patient under guardianship or tutorship
impossibility to submit at the study procedures due to geographic, social or mental reasons",1,0,0,0,0,1,18.0,200.0,Pleura,Brain,0,1,All
145,145,145,840,NCT03410121,2023-03-28,comparison of humeral or thoracic implantation of an central veinous access by an implantable venous access device in patients with solid tumors requiring chemotherapy,phase iv study comparing humeral or thoracic implantation of an central veinous access by an implantable venous access device in patients with solid tumors requiring intravenous chemotherapy,PACPAC-EPOC,interventional,"the aim of this study is to compare the humeral and thoracic implantation of a central venous access by an implantable device in patients with solids tumors who require intravenous chemotherapy. this is a monocentric randomized study. 572 patients will be recruited for 2 years. they will be randomized either in the thoracic implantation, either in the humeral implantation due to the 1:3 randomization, 143 patients will be randomized in the humeral arm and 429 into the thoracic one. number of complications related to the implantable device, medico-economic analysis as well as patient satisfaction will be assessed.

every patients with solid tumor requiring medical device implantation for intravenous chemotherapy treatment will be eligible.

both humeral and thoracic implantation of medical device are standard procedures. the randomization in a specific arm is the study procedure and is considered as an interventional study in france.","inclusion criteria:

patients with solid tumors at an advanced or metastasis stage requiring placement of implantable catheter for intravenous chemotherapy treatment
older than 18 years
express signed consent

exclusion criteria:

life expectancy less than 12 months assessed by investigator
infection or uncontrolled suspected infection
medical contraindication to port implantation by catheter in thoracic or humeral location
pregnant or lactating women
abnormal coagulation
immunosuppressed patients (for example known hepatitis b or c, or known positive human immunodeficiency virus due to the spreading risk)
patient not affiliated to the french social security
access time to the humeral or thoracic port placement higher than 15 days (from the randomization theoretical date)
protected adult or adult deprived of liberty",1,0,0,0,0,1,18.0,200.0,Vulva,Vulva,0,1,All
146,146,146,846,NCT03417336,2023-10-16,study evaluating the efficacy and the tolerance of pelvic-prostatic hypo-fractionated radiotherapy followed by boost in patients with prostate adenocarcinoma adverse intermediate risk or high localized risk,"multicenter, randomized, pilot study evaluating the efficacy and the tolerance of pelvic-prostatic hypo-fractionated radiotherapy followed by boost (stereotaxic external radiotherapy or high dose rate brachytherapy) in patients with prostate adenocarcinoma adverse intermediate risk or high localized risk",SHORT,interventional,"the standard treatment of high-risk prostatic adenocarcinoma is based on pelvic-prostatic external radiotherapy combined with concomitant and adjunctive hormone therapy for a total of 3 years.

prostatic stereotactic radiotherapy in 5 sessions is a therapeutic option currently delivered and described in multiple cohorts of patients with a tolerance comparable to normo-fractional treatments. this therapeutic scheme makes it possible to deliver a higher equivalent biological dose than during a treatment carried out with a conventional fractionation.

the results with a follow-up of 9 years are extremely encouraging and do not show any excess toxicity compared to other irradiation techniques. they confirm that urinary and digestive toxicities are acceptable. all these studies did not involve pelvic irradiation. several trials have also demonstrated the feasibility of normofractionated pelvic irradiation associated with hypofractionated prostatic irradiation using an integrated boost technique.

the primary objective is to evaluate, for localized high-risk prostate cancers (unfavorable intermediate or high risk), the rate of digestive and urinary toxicity cumulated at 3 months of the association of a pelvi-prostatic irradiation contracted in 5 sessions, with:to evaluate, for localized high-risk prostate cancers (unfavorable intermediate or high risk), the rate of digestive and urinary toxicity cumulated at 3 months of the association of a pelvi-prostatic irradiation contracted in 5 sessions, with:

a prostatic boost in brachytherapy with high dose rate (hdr) or
an integrated boost in stereotaxis (in case of contraindication to brachytherapy)","inclusion criteria:

adenocarcinoma of the prostate

patient with one of the following cases:

gleason 7 - 10 + t1c - t2b + psa < 50 ng/ml or
gleason 6 + t2c - t4 ou envahissement ≥ 50% sur les biopsies + psa < 50 ng/ml or
gleason 6 + t1c - t2b + psa > 20 ng/ml
risk of lymph node involvement> 15%
patient n0, or nx
prostate volume estimated on mri or ultrasound less than 60 cc.
absence of pelvic lymphadenopathy ≥ 15 mm on ct or mri extension assessment
lack of bone and / or visceral metastasis on ct scan and bone scintigraphy
hormonal treatment started maximum 90 days before the beginning of the irradiation,
ipss score <12 without alpha blocker treatment
absence of prior pelvic radiotherapy,
lack of surgical treatment for prostate cancer except transurethral resection performed within 6 months before radiotherapy,
age ≥ 18 years and ≤ 85 years,
who performance index ≤ 1,
estimated life expectancy> 5 years,
indication of treatment with radiotherapy and validated hormone therapy in a multidisciplinary consultation meeting
affiliation to a social security scheme,
signed informed consent.

exclusion criteria:

prostate cancer of histology other than adenocarcinoma,
patient diagnosed with n1 during imaging or pn1,
serum psa level> 100 ng / ml,
ipss score ≥ 12 or alpha blocker treatment,
prostate volume estimated on mri or ultrasound> 60 cc
history of cancer in the 5 years prior to entry into the trial,
history of trans-urethral resection of prostate less than 6 months old,
history of rectal surgery,
history of pelvic irradiation,
patient with severe hypertension not controlled by appropriate treatment,
contraindication to pelvic irradiation,

patient not eligible for brachytherapy

prostate volume> 60cc
urine flow measurement with max flow <12 ml / s
or curative anticoagulant treatment
or contraindication to general anesthesia
patient treated with antineoplastic or drug may include methotrexate,
hormone therapy started> 90 days before the first irradiation,
patient on immunosuppressant therapy
contraindication to agonists or antagonists of lhrh,
bilateral hip prosthesis,
patient already included in another therapeutic trial with an experimental molecule,
patient unable to cooperate during treatment,
persons deprived of their liberty or guardianship,
inability to undergo medical follow-up of the test.",1,0,0,0,0,1,18.0,85.0,Prostate,Prostate,0,0,Male
147,147,147,850,NCT03424005,2023-11-03,a study evaluating the efficacy and safety of multiple treatment combinations in patients with metastatic or locally advanced breast cancer,"a phase ib/ii, open-label, multicenter, randomized umbrella study evaluating the efficacy and safety of multiple treatment combinations in patients with metastatic breast cancer (morpheus-panbc)",Morpheus-panBC,interventional,"this is an umbrella study evaluating the efficacy and safety of multiple treatment combinations in participants with metastatic or inoperable locally advanced breast cancer.

the study will be performed in two stages. during stage 1, four cohorts will be enrolled in parallel in this study:

cohort 1 will consist of programmed death-ligand 1 (pd-l1)-positive participants who have received no prior systemic therapy for metastatic or inoperable locally advanced triple-negative breast cancer (tnbc) (first-line [1l] pd-l1+ cohort).

cohort 2 will consist of participants who had disease progression during or following 1l treatment with chemotherapy for metastatic or inoperable locally-advanced tnbc and have not received cancer immunotherapy (cit) (second-line [2l] cit-naive cohort).

cohort 3 will consist of participants with locally-advanced or metastatic hr+, her2-negative disease with pik3ca mutation who may or may not have had disease progression during or following previous lines of treatment for metastatic disease (hr+cohort).

cohort 4 will consist of participants with locally-advanced or metastatic her2+ /her2-low disease with pik3ca mutation who had disease progression on standard-of-care therapies (her2+ /her2-low cohort).

in each cohort, eligible participants will initially be assigned to one of several treatment arms (stage 1). in addition, participants in the 2l cit-naïve cohort who experience disease progression, loss of clinical benefit, or unacceptable toxicity during stage 1 may be eligible to continue treatment with a different treatment combination (stage 2), provided stage 2 is open for enrollment.","inclusion criteria

patients must meet all of the following criteria to qualify for stage 1 (all cohorts) and to qualify for stage 2 (2l cit-naïve cohort):

age >/= 18 years at the time of signing informed consent form
ecog performance status of 0 or 1
able to comply with the study protocol, in the investigator's judgment
metastatic or inoperable locally advanced breast cancer
measurable disease (at least one target lesion) according to recist v1.1
life expectancy >/= 3 months, as determined by the investigator
tumor accessible for biopsy
availability of a representative tumor specimen that is suitable for biomarker analysis via central testing
adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment
for women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from breastfeeding and donating eggs, as outlined for each specific treatment arm
for men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as outlined for each specific treatment arm

inclusion criteria for cohort 1

metastatic or inoperable locally advanced, histologically documented tnbc
no prior systemic treatment for metastatic or inoperable locally advanced tnbc
positive pd-l1 expression, defined as >/= 1% of the tumor area occupied by pd l1-expressing tumor-infiltrating immune cells of any intensity, as determined through use of the u.s. food and drug administration-approved or ce-marked ventana pd-l1 (sp142) assay

inclusion criteria for cohort 2

metastatic or inoperable locally advanced, histologically documented tnbc
eligible for capecitabine monotherapy
radiologic/objective evidence of recurrence or disease progression after 1l treatment with chemotherapy, for a total of one line of therapy for inoperable locally advanced or metastatic breast cancer

inclusion criteria for cohort 3

metastatic or inoperable locally-advanced, histologically documented hr+ breast cancer who had previous lines of treatment for metastatic disease.
fasting glucose < 126 mg/dl or < 7.0 mmol/l and hba1c </= 6.4%
confirmation of pik3ca mutation
patients for whom et (e.g., fulvestrant) is recommended and treatment with cytotoxic chemotherapy is not indicated at time of entry into the study, as per national or local treatments standards
postmenopausal, or premenopausal/perimenopausal status and willing to undergo and maintain treatment with approved lhrh-agonist (also known as gonadotropin-releasing hormone-agonist) therapy for the duration of study

inclusion criteria for cohort 4

left ventricular ejection fraction, measured by echocardiogram or radionucleotide ventriculography, greater than 50%
confirmation of her2+ or her2-low status fasting glucose < 126 mg/dl or < 7.0 mmol/l and hba1c </= 6.4%
confirmation of pik3ca mutation

exclusion criteria for stage 1

prior treatment with t-cell co-stimulating or immune checkpoint blockade therapies, including anti-ctla-4, anti-pd-1, and anti-pd-l1 therapeutic antibodies, cd40 agonists or interleukin-2 (il-2) or il-2-like compounds
treatment with investigational therapy within 28 days prior to initiation of study treatment
biologic treatment (e.g., bevacizumab) within 2 weeks prior to initiation of study treatment, or other systemic treatment for tnbc within 2 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
adverse events from prior anti-cancer therapy that have not resolved to grade </= 1 or better with the exception of alopecia of any grade and grade </= 2 peripheral neuropathy
eligibility only for the control arm

exclusion criteria for stage 1 (both cohorts) and stage 2 (2l cit-naïve cohort)

uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
uncontrolled tumor-related pain
symptomatic, untreated, or actively progressing central nervous system (cns) metastases
history of leptomeningeal disease
active or history of autoimmune disease or immune deficiency
history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (ct) scan. history of radiation pneumonitis in the radiation field (fibrosis) is permitted.
active tuberculosis
severe infection within 4 weeks prior to initiation of study treatment
treatment with therapeutic oral or iv antibiotics within 2 weeks prior to initiation of study treatment
significant cardiovascular disease
prior allogeneic stem cell or solid organ transplantation
history of malignancy other than breast cancer within 2 years prior to screening, with the exception of those with a negligible risk of metastasis or death
treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor alpha agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study
pregnancy or breastfeeding, or intention of becoming pregnant during the study

exclusion criteria for the 2l cit-naive cohort, stage 1

prior treatment with capecitabine,
treatment with sorivudine or its chemically related analogues, such as brivudine
history of severe and unexpected reactions to fluoropyrimidine therapy
known complete absence of dihydropyrimidine dehydrogenase activity

exclusion criteria for stage 2

inability to tolerate atezolizumab during stage 1
for patients receiving eribulin: congenital long qt syndrome

additional drug-specific exclusion criteria may apply to stage 1 and 2.",1,1,1,0,0,0,18.0,200.0,Breast,Breast,0,0,All
148,148,148,853,NCT03428958,2023-06-27,"a safety, pharmacokinetic and efficacy study of nuc-3373 in combination with standard agents used in colorectal cancer treatment","a phase ib/ii open label study to assess the safety and pharmacokinetics of nuc-3373, a nucleotide analogue, given in combination with standard agents used in colorectal cancer treatment",,interventional,"this is a three-part study of nuc-3373 administered by intravenous (iv) infusion across two administration schedules, either as monotherapy or as part of various combinations with agents commonly used to treat crc (leucovorin, oxaliplatin, irinotecan, bevacizumab, cetuximab and panitumumab). the primary objective is to identify a recommended dose and schedule for nuc-3373 when combined with these agents.","inclusion criteria:

all patients

provision of written informed consent
have histological confirmation of crc with evidence of locally advanced/unresectable or metastatic disease
age ≥18 years
life expectancy of ≥12 weeks
ecog performance status 0 or 1
measurable disease as defined by recist v1.1
known ras and braf status. patients with wild-type kras tumours who are to be enrolled to a cohort that does not contain an egfr pathway inhibitor (arms 2a, 2b, 2c, 2d, 3a, 3b, 3c, 3d and 3e) must have received prior treatment with an egfr inhibitor, unless this was not standard of care according to relevant region-specific treatment recommendations. patients with braf v600e mutant tumours should have received prior treatment with encorafenib in combination with an egfr inhibitor, unless this was not standard of care according to relevant region-specific treatment recommendations
adequate bone marrow function as defined by: anc ≥1.5×10^9/l, platelet count ≥100×10^9/l (with no evidence of bleeding), and haemoglobin ≥9 g/dl
adequate liver function as defined by serum total bilirubin ≤1.5×uln, ast and alt ≤2.5×uln (or ≤5×uln if liver metastases present)
adequate renal function assessed as serum creatinine <1.5×uln or glomerular filtration rate ≥50 ml/min. this criterion does not apply to arm 1d.
serum albumin ≥3 g/dl
for the cohort in which the patient will participate, there are no contra-indications to receiving the approved partner combination drugs
ability to comply with protocol requirements
female patients of child-bearing potential must have a negative serum pregnancy test within 7 days prior to the first study drug administration. this criterion does not apply to patients who have had a previous hysterectomy or bilateral oophorectomy. male patients and female patients of child-bearing potential must agree to practice true abstinence or to use two highly effective forms of contraception, one of which must be a barrier method.
patients must have been advised to take measures to avoid or minimise exposure to uv light for the duration of study participation and for a period of 4 weeks following the last dose of study medication
male patients receiving oxaliplatin must have been offered advice on and/or sought counselling for conservation of sperm prior to the first dose of study medication

>3rd-line patients

received at least two prior lines of therapy for locally advanced or metastatic crc, including one fluoropyrimidine plus oxaliplatin and one fluoropyrimidine plus irinotecan containing regimen. previous treatment with soc regimens in combination with molecular targeted therapies is permitted and patients who received folfoxiri-based regimens in 1st-/2nd-line settings may be included.
patients due to receive nufox should be suitable for re-challenge with an oxaliplatin-based regimen
patients due to receive nufiri should be suitable for re-challenge with an irinotecan-based therapy

2nd-/3rd-line patients

received at least one but no more than two prior lines of fluoropyrimide-containing therapy in combination with oxaliplatin and/or irinotecan for locally advanced or metastatic crc. previous treatment with soc regimens in combination with molecular targeted therapies is permitted and patients who received folfoxiri-based regimens in 1st-/2nd-line settings may be included. 3rd-line patients enrolled to arms 2c and 2d must have received prior bevacizumab treatment, unless ineligible or unless bevacizumab was not standard of care according to relevant region-specific treatment recommendations
patients in part 2 due to receive nufox should be suitable for re-challenge with an oxaliplatin-based regimen
patients in part 2 due to receive nufiri should be suitable for re-challenge with an irinotecan-based regimen

combination chemotherapy ineligible patients

may have received one prior fluoropyrimidine-containing regimen for locally advanced or metastatic crc
ineligible to receive combination therapy for locally advanced or metastatic crc
creatinine clearance >30ml/min

rapid progressors

received no more than two prior lines of fluoropyrimidine-containing therapy in combination with oxaliplatin and/or irinotecan for locally advanced or metastatic crc. previous treatment with soc regimens in combination with molecular targeted therapies is permitted and patients who received folfoxiri-based regimens in 1st-/2nd-line settings may be included.
have had tumour progression ≤3 months of starting the last fluoropyrimide-containing regimen
patients due to receive nufox should be suitable for re-challenge with an oxaliplatin-based regimen
patients due to receive nufiri should be suitable for re-challenge with an irinotecan-based regimen

2nd-line patients

1. received one prior line of fluoropyrimidine-containing therapy in combination with oxaliplatin and/or irinotecan for locally advanced or metastatic crc. previous treatment with soc regimens in combination with molecular targeted therapies is permitted and patients who received triplet chemotherapy based regimens is allowed.

maintenance patients

received at least 12 weeks of 1st-line soc therapy for locally advanced or metastatic crc and achieved at least stable disease
eligible for maintenance therapy

exclusion criteria:

all patients

prior history of hypersensitivity or current contra-indications to 5-fu or capecitabine
prior history of hypersensitivity or current contra-indications to any of the combination agents required for the study arm to which the patient is assigned
history of allergic reactions attributed to the components of the nuc-3373 drug product formulation
symptomatic cns or leptomeningeal metastases
symptomatic ascites, ascites currently requiring drainage procedures or ascites requiring drainage over the prior 3 months
chemotherapy, radiotherapy (other than short cycle of palliative radiotherapy [e.g. for bone pain]), immunotherapy or exposure to another investigational agent within 28 days (or five times half-life for a biological or molecular targeted agent or three times the half-life for an immunotherapy agent) of first receipt of study drug
residual toxicities from prior chemotherapy or radiotherapy, which have not regressed to grade ≤1 severity (ctcae v5.0) except for alopecia. in cohorts not containing oxaliplatin, residual grade 2 neuropathy is allowed.
history of another malignancy diagnosed within the past 5 years, with the exception of adequately treated non-melanoma skin cancer curatively treated carcinoma in situ of the cervix, surgically excised or potentially curatively treated ductal carcinoma in situ of the breast, or low grade prostate cancer or patients after prostatectomy not requiring treatment. patients with previous invasive cancers are eligible if treatment was completed more than 3 years prior to initiating the current study treatment and there is no evidence of recurrence.
presence of active bacterial or viral infection (including sars-cov-2, herpes zoster or chicken pox), known hiv positive or known active hepatitis b or c
presence of any uncontrolled concurrent serious illness, medical condition or other medical history, including laboratory results, which, in the investigator's opinion, would be likely to interfere with their participation in the study, or with the interpretation of the results
any condition (e.g. known or suspected poor compliance, psychological instability, geographical location) that, in the judgment of the investigator, may affect the patient's ability to sign the informed consent and undergo study procedures
currently pregnant, lactating or breastfeeding
qtc interval >450 milliseconds for males and >470 milliseconds for females
required concomitant use of drugs known to prolong qt/qtc interval
required concomitant use of strong cyp3a4 inducers or strong cyp3a4 inhibitors, or use of strong cyp3a4 inducers within 2 weeks of first receipt of study drug or use of strong cyp3a4 inhibitors within 1 week of first receipt of study drug
for patients receiving irinotecan: use of strong ugt1a1 inhibitors within 1 week of first receipt of study drug
has received a live vaccination within four weeks of first planned dose of study medication
known dpd or tymp mutations associated with toxicity to fluoropyrimidines
use of warfarin and other types of long acting anti-coagulants is prohibited within 4 weeks of the first dose of study treatment

patients receiving bevacizumab

patients with a history of haemoptysis (≥1/2 tsp of red blood)
wound healing complications or surgery within 28 days of starting bevacizumab
severe chronic wounds, ulcers or bone fracture
arterial thromboembolic events or haemorrhage within 6 months prior to study entry (except for tumour bleeding surgically treated by tumour resection)
bleeding diatheses or coagulopathy
receiving full-dose anti-coagulation treatment
uncontrolled hypertension
clinically significant coronary heart disease or myocardial infarction within the last 12 months or high risk of uncontrolled arrhythmia
severe proteinuria
acute or subacute ileus, chronic inflammatory bowel disease or chronic diarrhoea
any contraindications present in the bevacizumab prescribing information

patients receiving cetuximab or panitumumab

clinically significant coronary heart disease or myocardial infarction within the last 12 months or high risk of uncontrolled arrhythmia
acute or subacute ileus, chronic inflammatory bowel disease or chronic diarrhoea
hypomagnesaemia or hypokalaemia not controlled by oral therapy
any contraindications present in the cetuximab or panitumumab prescribing information",1,1,1,0,0,0,18.0,200.0,Colon,Colon,0,0,All
149,149,149,859,NCT03435796,2023-10-31,long-term follow-up protocol for participants treated with gene-modified t cells,long-term follow-up protocol for subjects treated with gene-modified t cells,,interventional,"this is a prospective study for the long-term follow-up (ltfu) of safety and efficacy for all pediatric and adult participants exposed to gene-modified (gm) t cell therapy participating in a previous celgene sponsored or celgene alliance partner sponsored study.

participants who received at least one gm t cell infusion will be asked to enroll in this ltfu protocol upon either premature discontinuation from, or completion of the prior parent treatment protocol.","inclusion criteria:

received at least one gene-modified (gm) t-cell infusion in a previous celgene sponsored or celgene alliance partner-sponsored study, and have discontinued, or completed the post-treatment follow-up period in the parent treatment protocol, as applicable.
must understand and voluntarily sign an informed consent form/informed assent form prior to any study-related assessments/procedures being conducted.

exclusion criteria:

not applicable

other protocol-defined inclusion/exclusion criteria apply",1,0,1,1,0,0,0.0,200.0,Other,Other,0,0,All
150,150,150,860,NCT03436485,2023-03-22,safety and pharmacokinetics of odm-208 in patients with metastatic castration-resistant prostate cancer,safety and pharmacokinetics of odm-208 in patients with metastatic castration-resistant prostate cancer,CYPIDES,interventional,the purpose of this first-in-man study is to evaluate safety and tolerability of odm-208 in patients with metastatic castration-resistant prostate cancer.,"main inclusion criteria:

written informed consent (ic) obtained.
male aged ≥ 18 years.
histologically confirmed adenocarcinoma of the prostate.
castration resistant prostate cancer with serum testosterone < 50 ng/dl.
metastatic disease.
ongoing androgen deprivation therapy with gnrh analogue or antagonist, or have had bilateral orchiectomy.
received at least one prior line of novel hormonal androgen receptor (ar) targeted therapy (e.g. abiraterone, enzalutamide).
ecog performance status 0-1.
adequate marrow, liver and kidney function.
able to swallow study treatment.
part 1: treatment with at least 1 line of chemotherapy or ineligibility for chemotherapy. part 2: treatment with at least 1 line of taxane-based chemotherapy in castration-sensitive prostate cancer (cspc) or in crpc.
part 2: identified activating mutation in the lbd of ar in plasma ctdna confirmed by the central testing.

main exclusion criteria:

history of pituitary or adrenal dysfunction.
known brain metastases or active leptomeningeal disease.
active infection or other medical condition that would make corticosteroid contraindicated.
poorly controlled diabetes.
hypotension or uncontrolled hypertension.
clinically significantly abnormal serum potassium or sodium level.
active or unstable cardio/cerebro-vascular disease including thromboembolic events.
prolonged qtcf interval.",1,1,1,0,0,0,18.0,200.0,Prostate,Prostate,0,0,Male
151,151,151,861,NCT03438552,2023-11-06,efficacy of repeat stereotactic radiation in patients with intraprostatic tumor recurrence,phase i/ii multi-center study evaluating the efficacy of repeat stereotactic radiation in patients with intraprostatic tumor recurrence after external radiation therapy,STEREO-RE-PRO,interventional,"stereo-re-pro aims to provide further evidence of stereotactic body radiotherapy (sbrt) as a supplementary non-invasive curative treatment for local recurrence following radiotherapy.

the objective of the first part of the trial (phase i) is to select the recommended dose for salvage sbrt (either 5 x 6 gy, 6 x 6 gy, or 5 x 5 gy) based on dose-limiting toxicity observed during the 18 weeks following the initiation of salvage-sbrt. particular attention will be paid to the quality of life and tolerance of the treatment.

the objective of the second part of the trial (phase ii) is to estimate the efficacy of the salvage-sbrt in terms of biochemical relapse-free survival rate.","inclusion criteria:

biochemical recurrence occurring at least 2 years after external radiotherapy for prostatic adenocarcinoma by the phoenix definition (psa nadir + 2 ng/ml)
t1-t2c and psa ≤20 ng/ml and gleason score ≤7 at initial diagnosis of prostate cancer before the initial/first treatment.
recurrence of prostatic adenocarcinoma proven by histology following radiotherapy by transrectal or transperineal sextant biopsies of the two lobes of the prostate, with a minimum of 12 biopsies, irrespective of gleason score. biopsies of the seminal vesicles are optional.
clinical stage t1-t2 on relapse; unilateral extracapsular extension (t3a) on mri permitted except posteriorly relative to the rectum
estimated clinical target volume (ctv) / prostate volume < 0.5 based on imaging and biopsies
pelvic and prostatic assessment by multiparametric mri- absence of pelvic or metastatic recurrence proven by choline pet scan
performance status world health organization (who) 0-1
psa level ≤10 ng/ml at baseline (before salvage-sbrt)
psa doubling time >10 months
international prostate cancer score (ipss) ≤12
uroflowmetry with a maximum flow rate >10 ml/s, a postvoid residual urine volume <150 ml, and a urine volume >150 ml.
no other anti-cancer treatment since the external radiotherapy administered as first-line treatment
no other anti-cancer treatment planned for the current recurrence
no contraindication to fiducial marker implants; haemostatic disorders must be corrected before implantation
age >18 years
life-expectancy greater than or equal to 5 years (lee scale)
patient registered with a health insurance system
patient who has signed the informed consent form
patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol.

exclusion criteria:

lymph node or metastatic spread
late post-radiotherapy urinary or gastrointestinal toxicity of grade ≥2 (following primary radiotherapy)
other cancers in the last 5 years except for non-melanoma-type skin cancer
history of inflammatory bowel disease
anticoagulant treatment
contraindications to undergoing mri
prostate volume >80 cc
transurethral resection of the prostate (turp) in the 6 months before registrations
presence of rectal telangiectasia grade 3 classified by the vienna rectoscopy score (obligatory rectoscopy)
previous rectal surgery
patients unable to undergo medical follow-up in the study for geographical, social or psychological
person deprived of their liberty or under protective custody or guardianship
patients enrolled in another therapeutic study

all patients during the sbrt planning with a ratio of clinical target volume (ctv) / prostate volume >0.5 will be withdrawn from the study. these patients will be considered as not evaluable and will not be treated within the context of the study.",1,0,0,0,0,1,18.0,200.0,Prostate,Prostate,0,0,Male
152,152,152,863,NCT03439371,2023-05-04,micro-transplantation in elderly patients with acute myeloid leukemia,"a phase ii, multicenter, open label study evaluating the efficacy and the tolerance of micro-transplantation in elderly patients with acute myeloid leukemia (mtsa)",MTSA,interventional,this study aims at evaluating the safety and the tolerance of the micro-transplantation in elderly patients with acute myeloid leukemia who are ineligible to conventional allogeneic transplantation.,"inclusion criteria:

patient affiliated to a social security regimen or beneficiary of the same
signed written informed consent form
patient, ≥ 60 years-old - < 75 years-old, with established diagnosis of de novo or secondary aml with intermediate-risk or adverse-risk cytogenetic profile, or with established myelodysplasic syndromes (raeb), in pathologically confirmed complete remission following anti-leukemic induction therapy (<5% blasts)
contra-indication to conditioning regimen in conventional allogeneic transplantation

exclusion criteria:

patient with established diagnosis of acute myeloid leukemia with standard-risk cytogenetic profile
promyelocytic leukemia t(15;17)
cbf-aml t(8;21) or inv(16)
normal karyotype with a favorable molecular profile: npm1+ and flt3-; npm1+, flt3- and double mutation cebpα or chronic myeloid leukemia in blastic phase
patient under guardianship or deprived of his liberty or any condition that may affect the patient's ability to understand and sign the informed consent
refusing participation",1,0,0,0,0,1,60.0,75.0,Pleura,Pleura,0,0,All
153,153,153,870,NCT03448042,2023-11-01,a study of runimotamab in participants with locally advanced or metastatic her2-expressing cancers,"a phase ia/ib, open-label, dose-escalation study of the safety and pharmacokinetics of runimotamab administered intravenously as a single agent and in combination with trastuzumab in patients with locally advanced or metastatic her2-expressing cancers",,interventional,"this study will evaluate the safety, tolerability, and pharmacokinetics of runimotamab administered intravenously as a single agent and in combination with trastuzumab in participants with locally advanced or metastatic human epidermal growth factor receptor 2 (her2)-expressing cancers.","inclusion criteria

eastern cooperative oncology group (ecog) performance status of 0 or 1
life expectancy of at least 12 weeks
adequate hematologic and end-organ function
acute, clinically significant treatment-related toxicity from prior therapy must have resolved to grade </=1 prior to study entry
left ventricular ejection fraction (lvef) >/=50%

her2-expressing breast cancer-specific inclusion criteria

locally tested, human epidermal growth factor receptor 2 (her2)-expressing bc
locally advanced or metastatic bc that has relapsed or is refractory to established therapies

her2-expressing gastric/gastroesophageal (gej) cancer-specific inclusion criteria

adenocarcinoma of the stomach or gej with inoperable locally advanced or recurrent and/or metastatic disease, not amenable to curative therapy
her2-expressing tumor (primary tumor or metastasis) as assessed by local lab testing
her2-positive gastric/gej cancer must have received prior trastuzumab, cisplatin (or carboplatin or oxaliplatin or investigational platinum agent) and 5-fluorouracil (5-fu)/capecitabine

her2-positive solid tumor specific inclusion criteria

her2-positive tumor (primary tumor or metastasis) as assessed by local (non-central) laboratory testing
locally advanced, recurrent, or metastatic incurable malignancy that has progressed after at least one available standard therapy; or for whom standard therapy has proven to be ineffective or intolerable, or is considered inappropriate; or for whom a clinical trial of an investigational agent is a recognized standard of care; or for whom a clinical trial of an investigational agent is considered an acceptable treatment option

exclusion criteria

pregnant or breastfeeding, or intending to become pregnant during the study or within 140 days after the last dose of runimotamab
significant cardiopulmonary dysfunction
known clinically significant liver disease
positive for acute or chronic hepatitis b virus (hbv) infection
acute or chronic hepatitis c virus (hcv) infection
human immunodeficiency virus (hiv) seropositivity
poorly controlled type 2 diabetes mellitus
history of ventricular dysrhythmias or risk factors for ventricular dysrhythmias
current treatment with medications that are well known to prolong the q-wave/t-wave (qt) interval
known clinically significant liver disease
primary central nervous system (cns) malignancy, untreated cns metastases, or active cns metastases (progressing or requiring corticosteroids for symptomatic control)
leptomeningeal disease
spinal cord compression that has not definitively treated with surgery and/or radiation
history of autoimmune disease
prior allogeneic stem cell or solid organ transplantation",1,1,0,0,0,0,18.0,200.0,Breast,Other,0,0,All
154,154,154,871,NCT03449264,2021-11-03,development of clinical and biological database,"development of a monocentric and prospective clinical and biological database in digestive cancers, gynecological cancers, breast cancers and sarcomas",BCBInstitut,interventional,"the bcb is a tool:

for research in analytical and public health epidemiology, biological research and for the development of data useful for clinical research and therapeutic trials;
to help scientists understand and explain phenomena ranging from the interaction of molecules to the whole metabolism of the organism in normal and pathological situations;
to identify potential strategies for prevention, diagnosis, management and analysis of cancer subtypes.

the creation of a broad clinical and biological prospective base dedicated to different types of cancer is essential for the development of such projects.","inclusion criteria:

age> at 18 years old,
patient with invasive or in situ tumor pathology (proven or suspected) any stage confounded,

patient in icm at diagnosis

a digestive cancer (esophagus, stomach, pancreas, colon, rectum, anal canal) or
gynecological cancer (ovary, endometrium, cervix) or
breast cancer or
sarcoma.
naïve patient of any treatment for the present cancer,
patient requiring treatment involving at least one (or more) tumor surgery (s)
patient who has accepted supplementary blood samples,
patient having given his informed, written and express consent.

exclusion criteria:

patient not affiliated to a social protection scheme,
patient whose regular follow-up is a priori impossible for psychological, familial, social or geographical reasons,
pregnant and / or nursing women,
subject under tutelage, curatorship or safeguard of justice,
patient in an emergency situation.",1,0,0,0,0,1,18.0,200.0,Pleura,Breast,0,1,All
155,155,155,880,NCT03467360,2023-01-19,inhibition of carbonic anhydrase in combination with platinum and etoposide-based radiochemotherapy in patients with localized small cell lung cancer,phase i trial of carbonic anhydrase inhibition associated with platinum-based chemotherapy and etoposide in concomitance with radiotherapy in localized small cell lung carcinomas,ICAR,interventional,"the investigators propose to study the carbonic anhydrase inhibition (acetazolamide) associated with concomitant radiochemotherapy in localized small cell lung cancer due to:

the over-expression of carbonic anhydrases in this type of cancer,
the anti-tumor effect in preclinical acetazolamide in various tumor lines including neuroendocrine tumor lines,
the observed synergy between irradiation and inhibition of carbonic anhydrases,
potential anti-tumor immune effect caused by decreased extracellular acidity.","inclusion criteria:

age > or = 18 years,
performance status 0 to 2,
patient with an histologically non-metastatic localized small cell lung cancer,
patient who must start radiotherapy treatment combined with chemotherapy with platinum and etoposide, note: the decision of the multidisciplinary consultation team must be notified in the patient's medical file,
evaluation lesion according to the criteria recist 1.1 and / or according to the criteria percist 1.0,
women of childbearing potential must have a negative serum pregnancy test within 72 hours of the first administration of the study treatment,
if the patient is a woman of childbearing potential, she must be surgically sterile or agree to use two adequate methods of contraception throughout the duration of the study until 1 month after the last administration of the study treatment. subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year, note: abstinence is acceptable if it is the patient's usual and preferred form of contraception,
if the male patient has one or more female partners of childbearing age, he / she must agree to use an adequate method of contraception, starting at the first administration of the study treatment up to 1 month after the last administration of the treatment. of the study, note: abstinence is acceptable if it is the patient's usual and preferred form of contraception,
patient willing and able to provide written informed consent/assent for the trial,
patient affiliated with a health insurance system.

exclusion criteria:

patient with metastatic disease,
history of thoracic irradiation or near / in the thoracic irradiation field,
patient who refuses to participate in the study or unable to agree,

contraindication to thoracic radiotherapy treatment: congestive heart failure unbalanced (ejection fraction <30%, clinical signs), severe respiratory failure:

copd grade iv according to the gold classification,
some gold iii copd and any patient with a respiratory defect defined as: oxygen dependence and / or fev1 <40% normal and / or, dlco <40% predictive value and / or vital capacity <40% predictive value,
contraindication to acetazolamide: hypersensitivity to acetazolamide, severe hepatic, renal or adrenal insufficiency, sulfonamide intolerance, history of renal colic, allergy to wheat other than celiac disease,
patient currently receiving one or more treatments described in section 6.9 of the protocol,
history of cancer, with the exception of cancers in complete remission for more than 5 years, completely resected basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer,
people particularly vulnerable as defined in articles l.1121-5 to -8 of the french healthcare code, including: person deprived of freedom by an administrative or judicial decision, adult being the object of a legal protection measure or outside a state to express their consent, pregnant or breastfeeding women",1,1,0,0,0,0,18.0,200.0,Lung,Lung,1,0,All
156,156,156,887,NCT03472807,2023-05-22,exome rare cancers in children (exocare),an investigation of susceptibility genes for rare cancers in children by exome sequencing,EXOCARE,interventional,"other than high-dose radiation and previous chemotherapy, few strong risk factors have been identified as causes of childhood cancer. geneticists estimate that 5 to 10% of all cancers diagnosed during the paediatric period occur in children born with a genetic mutation, increasing their lifetime risk of neoplasia. such genetic risk is higher in children with congenital anomalies and specific genetic syndromes. some germline genetic alterations are well known (e.g. p53 protein (p53), neurofibromatosis type 1(nf1)), however many children with none of these mutations have clinical presentations that strongly suggest the involvement of a genetic predisposition. comprehensive genetic testing for all such patients is an important factor for improving disease surveillance. such opportunities are now available thanks to whole exome sequencing (wes). in oncology, an important clinical application of wes will be to routinely identify mutations associated with inherited cancer predispositions and to guide cancer risk-management decisions.

our project is a national translational multicenter genetics study aimed at identifying genes involved in paediatric cancer predisposition by wes in a very select population of children with both developmental delay and cancer. our project relies on the ted register (tumeur et développement), an initiative by the french organisation sfce (société française de lutte contre les cancers et les leucémies de l'enfant et de l'adolescent) involving 30 child cancer units in france. this database includes the information of more than 500 paediatric cancer patients with congenital abnormalities. the investigators plan to sequence the germline and tumour exome of 100 patients with developmental delay in a trio-design consisting of 300 people and 100 tumours.

the investigators believe that the exocare project will provide answers to the genetic origins of certain particular childhood cancers. the exocare project relies on a genetic study to identify genetic risk factors for rare forms of childhood cancer and aims to establish more personalised treatment. it is aimed at improving genetic counselling for families and will be fully integrated in the genetic counselling process. the information provided by our study will be used to improve the management approach to an initial cancer by clarifying the risks of other cancers in related families. the investigators hope to identify new germline genes predisposing to cancer that will be of interest in understanding tumour biology.","inclusion criteria:

for ""patient cancer"" :

child having developed a cancer combined with a delay of development and\or an intellectual deficiency before the age of 18 years and followed for a cancer of the child in one of hospital center of the société française de lutte contre les cancers et les leucémies de l'enfant et de l'adolescent (sfce)
at least a parent still alive and available to make genetic analyses

for ""parent of cancer patient"" :

parent whose child meets the criteria of inclusion of ""cancer patient""

exclusion criteria:

for ""cancer patient"" :

genetic predisposition already identified at the child
absence of histological confirmation
child died without dna of the available germinal lineage

for ""parent of cancer patient"" :

parent whose child doesn't meets the criteria of inclusion of ""cancer patient""",1,0,0,0,0,1,0.0,200.0,Pleura,Pleura,0,0,All
157,157,157,890,NCT03474094,2023-01-26,clinical and biological activity of an anti-pd-l1 (atezolizumab) in operable localised soft tissue sarcomas patients to be treated with radiotherapy,"a european, multicenter, randomized, open-label, phase ii trial aiming to assess the clinical and biological activity of an anti-pd-l1 (atezolizumab) in operable localised soft tissue sarcomas patients to be treated with radiotherapy",RT-Immune,interventional,"this multicentric, randomised, phase ii trial will use a pick-the-winner design in order to evaluate the clinical and biological activity of atezolizumab when combined with pre-operative or post-operative radiotherapy in sts patients.

following inform consent form (icf) signature, eligible patients will be randomised (1:1:1) to receive:

arm a: radiotherapy followed by atezolizumab then surgery.
arm b: atezolizumab followed by surgery then radiotherapy.
arm c: radiotherapy then surgery followed by atezolizumab.

the sequence of the study treatments is different among the 3 study arms. however, the dose regimens will be the same:

atezolizumab will be administered to all patients at the dose of 1200mg, by iv injection, for 2 cycles (q3w).
radiotherapy will be administered to all patients at the dose of 2gy/day, 5 days per week, for a total of 5 weeks and 50gy.
surgery will be performed as per institutional practice.

randomisation will be stratified according to histological subtypes as follows:

group 1: liposarcoma (lps), undifferentiated pleomorphic sarcoma (ups), leiomyosarcoma (lms), myxofibrosarcoma, angiosarcoma versus group 2: all translocation sarcoma except ewing, rhabdomyosarcoma (rms) and myxoid lps.","inclusion criteria:

male or female patients aged ≥ 18 years at time of inform consent signature.
histologically confirmed soft tissue sarcoma including liposarcoma, leiomyosarcoma, myxofibrosarcoma, ups, angiosarcoma, all translocation sarcoma except ewing, rhabdomyosarcoma (rms), and myxoid liposarcoma (lps).

soft tissue sarcoma suitable for neoadjuvant rt and amenable to surgery with curative intent (high-grade non-metastatic tumors, intermediate and low-grade tumors greater than 5 cm).

note: patients with local relapsing disease amenable to surgery are eligible.

presence of at least one tumor lesion with a diameter ≥10 mm, visible by medical imaging and accessible to percutaneous or endoscopic sampling that permit core needle biopsy without unacceptable risk and suitable for retrieval of a minimum of three, but ideally 4, cores using a biopsy needle of at least 16-gauge.
eastern cooperative oncology group performance status (ecog ps) of 0 or 1 (appendix 4).

adequate end organs and bone marrow functions as defined below according to lab tests performed within 7 days before w1d1:

bone marrow (without transfusion within 2 weeks before w1d1):

hemoglobin ≥ 9.0 g/dl,
absolute neutrophil count ≥ 1.5 x 109/l,
platelets ≥ 100 x 109/l,
lymphocyte count ≥ 0.5 x 109/l.

renal function:

serum creatinine clearance ≥ 30 ml/min/1.73m2 (mdrd or ckd-epi formula - appendix 3)

hepatic function

serum bilirubin < 1.5 × upper limit of normal (uln), with the following exception: patients with known gilbert disease who have serum bilirubin level ≤ 3 uln may be enrolled.
aspartate aminotransferase (ast), alanine aminotransferase (alt) and alkaline phosphatase ≤ 2.5 uln.

coagulation

inr and aptt ≤ 1.5 uln note: this is applicable only for patients not receiving an anticoagulant treatment: patients receiving therapeutic anticoagulation must be on stable dose.

minimal wash-out period for prior treatments (minimal time required from the end date of prior treatment to w1d1):

immunosuppressive medication > 28 days, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid,
live attenuated vaccines > 30 days, note: seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., flu-mist®) are live attenuated vaccines, and are not allowed.
major surgical procedure, open biopsy (excluding skin cancer resection and screening tumor biopsy), or significant traumatic injury > 14 days (the wound must have healed),
any approved or investigational anti-cancer therapy, including chemotherapy, hormonal therapy or targeted therapy > 21 days,
systemic immunostimulatory agents > 28 days or five half-lives of the drug, whichever is longer,
oral or iv antibiotics > 14 days.
women of child-bearing potential must have a negative serum pregnancy test within 7 days before randomisation and must agree to use an effective form of contraception from the time of the negative pregnancy test up to 5 months after the last dose of atezolizumab (see appendix 5).
fertile men must agree to use an effective method of birth control during the study and for up to 5 months after the last dose of atezolizumab.
patient should understand, sign, and date the written voluntary informed consent form prior to any protocol-specific procedures performed. patient should be able and willing to comply with study visits and procedures as per protocol.
patients must be covered by a medical insurance in country where applicable.

exclusion criteria:

patients with evidence of metastatic disease, defined by the presence of any of the followings:

lesions that are discontinuous from the primary tumor,
lesions that are not regional lymph nodes,
lesions that do not share a body cavity with the primary tumor,
evidence by medical imagining (eg ct-scan) of metastatic disease.

patients with history of severe allergic or other hypersensitivity reactions to:

chimeric or humanized antibodies or fusion proteins,
biopharmaceuticals produced in chinese hamster ovary cells, or
any component of the atezolizumab formulation.

patients using or requirement to use while on the study of any not permitted concomitant medications :

any approved anti-cancer systemic treatment including chemotherapy, hormonotherapy, biological therapy, immunotherapy other than atezolizumab,
any investigational agents,
live vaccines. examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, bcg, and typhoid (oral) vaccine. seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however intranasal influenza vaccines (e.g. flu-mist®) are live attenuated vaccines, and are not allowed during the study active period,
traditional herbal medicines since the ingredients of many herbal medicines are not fully studied and their use may result in unanticipated drug-drug interactions that may cause or confound assessment of toxicity,
immunostimulatory agents, including but not limited to ifn-α, ifn-γ, or il-2, during the entire study. these agents, in combination with atezolizumab, could potentially increase the risk for autoimmune conditions. in addition, all patients (including those who discontinue the study early) should not receive other immunostimulatory agents for 10 weeks after the last dose of atezolizumab,
immunosuppressive medications, including but not limited to cyclophosphamide, azathioprine, methotrexate, and thalidomide. these agents could potentially alter the activity and the safety of atezolizumab. systemic corticosteroids and anti-tnf-α agents may attenuate potential beneficial immunologic effects of treatment with atezolizumab but may be administered to manage irae (see safety plan). if feasible, alternatives to these agents should be considered.
patients with a malignancy other than sts within 5 years prior to randomisation with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated in situ carcinoma of the cervix, basal or squamous cell skin cancer, localised prostate cancer or ductal in situ carcinoma treated surgically with curative intent).
patients with severe infections within 4 weeks prior to randomisation including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia.

patients with history of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, wegener's granulomatosis, sjögren's syndrome, guillain-barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.

note: patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:

rash must cover less than 10% of body surface area (bsa).
disease is well controlled at baseline and only requiring low potency topical steroids.
no acute exacerbations of underlying condition within the previous 12 months (not requiring puva [psoralen plus ultraviolet a radiation], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, high-potency or oral steroids)"" note: patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible.

note: patients with a type i diabetes well controlled by a stable dose of insulin are eligible.

patients with active b or c hepatitis infection. note: patients with past hepatitis b virus (hbv) infection or resolved hbv infection (defined as having a negative hbsag test and a positive antibody to hepatitis b core antigen [anti-hbc] antibody test) are eligible. patients positive for hepatitis c virus (hcv) antibody are eligible only if polymerase chain reaction (pcr) is negative for hcv rna.
patients with active tuberculosis.

patients with ongoing toxicities (grade ≥1 according to ctcae v5.0) from previous therapies, except for alopecia (any grades) and lab values defined in inclusion criteria.

note: some grade 2 may be permitted following discussion with the sponsor.

patients with evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome).

patients with significant cardiovascular disease, such as new york heart association cardiac disease class ii or greater, myocardial infarction within 3 months prior to w1d1, unstable arrhythmias or unstable angina.

notes:

patients with a known left ventricular ejection fraction (lvef) < 40% will be excluded
patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or lvef < 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate.
patients with history of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on imaging.
pregnant or lactating women.
prior organ transplantation including allogeneic stem cell transplantation.
patients who are known to be serologically positive for human immunodeficiency virus (hiv).

e16. patient with prior treatment with anti-pd-1, or anti-pd-l1 immune checkpoint blockade therapies.",1,0,1,0,0,0,18.0,200.0,Other,Pleura,0,0,All
158,158,158,892,NCT03475953,2023-03-02,a phase i/ii study of regorafenib plus avelumab in solid tumors,a phase i/ii study of regorafenib plus avelumab in solid tumors,REGOMUNE,interventional,"assessment of the efficacy and safety of regorafenib and avelumab in patients with advanced or metastatic solid tumors (ten cohorts), once the recommanded phase ii dose (rp2d) has been determined (phase i trial).

assessement of the efficacy and safety of a low-dose of regorafenib (80mg/day) with avelumab in patients with advanced or metastatic colorectal tumors.","inclusion criteria :

histology:

dose escalation part: histologically confirmed non msi-h or deficient-mmr colorectal cancer, or gist, or esophageal or gastric carcinoma or hepatobiliary cancers,

phase ii trials : histologically confirmed

non msi-h or deficient-mmr colorectal cancer (cohort a),
or gist (cohort b). as recommended diagnosis by inca, patients with gist must have histologically confirmed by central review, except if it has been already confirmed by the rreps network
or esophageal or gastric carcinoma (cohort c),
or hepatobiliary cancers (cohort d),
or soft-tissue sarcoma (sts) (cohort e). as recommended diagnosis by inca, patients with sts must have histologically confirmed by central review, except if it has been already confirmed by the rreps network
or radioiodine-refractory differentiated thyroid cancer [rr-dtc] (cohort f),
or neuroendocrine gastroenteropancreatic tumors grade 2 and 3
or non-small cell lung cancer (cohort h)
or solid tumors including soft-tissue sarcoma with immune signature (cohort i), i.e. presence of tertiary lymphoid structures on tumor sample as determined by central review.
or urothelial cancer (cohort j)
or hpv-associated cancer (cohort k) with molecular confirmation p16 positive status,
triple negative breast cancer (cohort l)
or tmb-high solid tumors (cohort m) with status tmb-high already known
or msi-high solid tumors (cohort n) with status msi-high already known
or non clear-cell renal carcinoma (cohort o)
or malignant pleural mesothelioma (cohort p).
advanced non resectable / metastatic disease,
patients for which either there is no further established therapy that is known to provide clinical benefit, or (for patients to be treated with 160 mg regorafenib) regorafenib monotherapy is an approved or established therapeutic option,
age ≥ 18 years,
ecog, performance status ≤ 1,
measurable disease according to recist,
life expectancy > 3 months,
except for cohorts f and h, ≥ 1 previous line (s) of systemic therapy,

adequate hematological, renal, metabolic and hepatic functions:

hemoglobin ≥ 9 g/dl (patients may have received prior red blood cell [rbc] transfusion, if clinically indicated); absolute neutrophil count (anc) ≥ 1.5 x 109/l and platelet count ≥ 100 x 109/l, lymphocytes ≥ 1000/mm3.
alkaline phosphatase (ap), alanine aminotransferase (alt) and aspartate aminotransferase (asp) ≤ 2.5 x upper limit of normality (uln) (≤ 5 in case of extensive skeletal involvement for ap and/or liver metastasis and ≤ 5 x uln in case of liver metastasis for ast and alt).
total bilirubin ≤ 1.5 x uln.
albumin ≥ 25g/l.
calculated creatinine clearance (crcl) ≥ 30 ml/min (according to cockroft and gault formula).
creatine phosphokinase (cpk) ≤ 2.5 x uln.
inr < 1.5 x uln
aptt ≤ 1.5 x uln
lipase ≤ 1.5 x uln.
cohort specific criteria: patients with hepatocellular carcinoma must have a correct hepatocellular function, id est child-pugh a.
no prior or concurrent malignant disease diagnosed or treated in the last 2 years except for adequately treated in situ carcinoma of the cervix, basal or squamous skin cell carcinoma, or in situ transitional bladder cell carcinoma,
at least three weeks since last chemotherapy, immunotherapy or any other pharmacological treatment and/or radiotherapy,
recovery to grade ≤ 1 from any adverse event (ae) derived from previous treatment, excluding alopecia of any grade and non-painful peripheral neuropathy grade ≤ 2 (according to the national cancer institute common terminology criteria for adverse event (nci-ctcae, version 5.0)),
women of childbearing potential must have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study medication,
both women and men must agree to use an highly effective method of contraception throughout the treatment period and for eight weeks after discontinuation of treatment. acceptable methods for contraception are described in protocol section 7.4.1,
voluntary signed and dated written informed consents prior to any specific study procedure,
patients with a social security in compliance with the french law.
documented disease progression (as per recist v1.1) before study entry. for patients of cohort e (sts) and cohort i (solid-tumors - tls+): this progression will be confirmed by central review on the basis of two ct scan or mri obtained not less than 6 months in the period of 12 months prior to inclusion. for patients of cohort f (rr-dtc): this progression will be confirmed by central review on the basis of two ct scan or mri obtained at less than 12 months prior to inclusion.
for patients in cohort h: subjects with histologically or cytologically confirmed diagnosis of non-squamous nsclc. documents disease progression based on radiographic imaging, during or after a maximum of 2 lines of systemic treatment for locally/regionally advanced recurrent, stage iiib/iv or metastatic disease. two components of treatments must have been received in the same line or as separate lines of therapy: a maximum of 1 line of platinum-containing chemotherapy regimen, and a maximum of 1 line of pd(l)1 mab containing regimen. no egfr, alk, ros1 positive tumor mutations. subjects with known braf molecular alterations must have had disease progression after receiving the locally available soc treatment for the molecular alteration

for patients with urothelial cancer (cohort j):

a maximum of 1 line of pd(l)1 mab containing regimen, and
patients must have received at least 4 months of pd(l1) mab treatment.

for hpv-associated cancer (cohort k), tmb-high solid tumors (cohort m) msi-high solid tumors (cohort n), non clear-cell renal carcinoma (cohort o):

o no previous line of pd(l)1 mab containing regimen

for malignant pleural mesothelioma (cohort p):

a maximum of 1 line of pd(l)1 mab containing regimen, and
patients must have received at least 4 months of pd(l1)/ ctla-4 mab treatment in the case they received this treatment

for triple-negative breast cancer patients (cohort l)

a maximum of 1 line of pd(l)1 mab containing regimen, and
patients must have received at least 4 months of pd(l1) mab treatment

for tmb-high cancer patients (cohort m):

tmb-high is defined as tmb score > 16 mutations /megabase on tissue or blood sample

exclusion criteria:

previous treatment with avelumab or regorafenib,
has received prior therapy with an anti-pd-1, anti-pd-l1, anti-pd-l2, anti-cd137, or anti-cytotoxic t-lymphocyte-associated antigen-4 (ctla-4) antibody (including ipilimumab or any other antibody or drug specifically targeting t-cell costimulation or checkpoint pathways), except for cohort h (nsclc), cohort i (solid tumors (including soft tissue sarcoma) with immune signature (tls+)) and cohort p (malignant pleural mesothelioma),
evidence of progressive or symptomatic or newly diagnosed central nervous system (cns) or leptomeningeal metastases,
men or women of childbearing potential who are not using an effective method of contraception as previously described;
participation to a study involving a medical or therapeutic intervention in the last 30 days,
previous enrolment in the present study,
patient unable to follow and comply with the study procedures because of any geographical, familial, social or psychological reasons,
known hypersensitivity to any involved study drug or of its formulation components,

active autoimmune disease that might deteriorate when receiving an immunostimulatory agent :

subjects with diabetes type i, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible
subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses ≤ 10 mg or 10 mg equivalent prednisone per day
administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) are acceptable
has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment,
history of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest ct scan or interstitial lung disease with ongoing signs and symptoms at inclusion. history of radiation pneumonitis in the radiation field (fibrosis) is permitted,
has known hepatitis b or hepatitis c, active and/or treated by antiviral therapy
has a known history of human immunodeficiency virus (hiv) (hiv1/2 antibodies) or known acquired immunodeficiency syndrome (aids),
spot urine must not show 1+ or more protein in urine or the patient will require a repeat urine analysis,
major surgical procedure or significant traumatic injury within 28 days before start of study medication,
non-healing wound, non-healing ulcer, or non-healing bone fracture requiring orthopedic treatment,
patients with evidence or history of any bleeding diathesis, irrespective of severity,
any hemorrhage or bleeding event ≥ ctcae grade 3 within 4 weeks prior to the start of study medication,
arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before the start of study medication (except for adequately treated catheter-related venous thrombosis occurring more than one month before the start of study medication),
ongoing infection > grade 2 as per nci ctcae v5.0,
uncontrolled hypertension (systolic blood pressure > 140 mmhg or diastolic pressure > 90 mmhg) despite optimal medical management,
congestive heart failure ≥ new york heart association (nhya) class 2,
unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months),
myocardial infarction less than 6 months bedfore start of study drug,
uncontrolled cardiac arrhythmias,
pregnant or breast-feeding patients,
individuals deprived of liberty or placed under legal guardianship,
prior organ transplantation, including allogeneic stem-cell transplantation,
known alcohol or drug abuse,
vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines,
patients with any condition that impairs their ability to swallow and retain tablets,
other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study,
patient with oral anticoagulation therapy,
suspected or known intraabdominal fistula.
for cohort h: received more than 2 prior lines of therapy for nsclc, including subjects with braf molecular alteration and subjects with knwon egfr/alk/ros1 molecular alterations are excluded",1,1,1,0,0,0,18.0,200.0,Pleura,Pleura,0,0,All
159,159,159,895,NCT03485209,2023-11-03,efficacy and safety study of tisotumab vedotin for patients with solid tumors,open label phase 2 study of tisotumab vedotin for locally advanced or metastatic disease in solid tumors,innovaTV 207,interventional,"this trial will study tisotumab vedotin to find out whether it is an effective treatment for certain solid tumors and what side effects (unwanted effects) may occur. there are seven parts to this study.

in part a, the treatment will be given to participants every 3 weeks (3-week cycles).
in part b, participants will receive tisotumab vedotin on days 1, 8, and 15 every 4-week cycle.
in part c, participants will receive tisotumab vedotin on days 1 and 15 of every 4-week cycle.

in part d, participants will be given treatment on day 1 of every 3-week cycle. participants in part d will get tisotumab vedotin with either:

pembrolizumab or,
pembrolizumab and carboplatin, or
pembrolizumab and cisplatin
in part e, participants will receive tisotumab vedotin on days 1 and 15 of every 4-week cycle.
in part f, participants will receive tisotumab vedotin on days 1, 15, and 29 of every 6-week cycle. participants in part f will get tisotumab vedotin with pembrolizumab.
in part g, participants will receive tisotumab vedotin on days 1, 15, and 29 of every 6-week cycle. participants in part g will get tisotumab vedotin with pembrolizumab and carboplatin.","inclusion criteria:

parts a, b, and c

relapsed, locally-advanced or metastatic colorectal or pancreatic cancer, sqnsclc, or scchn participants who are not candidates for standard therapy.
all participants must have experienced disease progression on or after their most recent systemic therapy.
colorectal cancer (closed to enrollment): participants must have received prior therapy with each of following agents, if eligible: a fluoropyrimidine, oxaliplatin, irinotecan, and/or bevacizumab. participants should have received no more than 3 systemic regimens in the metastatic setting.

sqnsclc (closed to enrollment): participants with nsclc must have predominant squamous histology. participants must have received prior therapy with a platinum-based treatment and a checkpoint inhibitor (cpi), if eligible. participants should have received no more than 3 lines of systemic therapy in the metastatic setting.

participants eligible for a tyrosine kinase inhibitor should have received such therapy. these participants should have received no more than 4 lines of systemic therapy in the metastatic setting.
exocrine pancreatic adenocarcinoma (closed to enrollment): participants with exocrine pancreatic adenocarcinoma must have predominant adenocarcinoma histology. participants must have received prior therapy with a gemcitabine-based or 5fu-based regimen, if eligible, and should have received no more than 1 systemic regimen in the unresectable or metastatic setting.
scchn (closed to enrollment): participants with scchn in part c must have received prior therapy with a platinum-based regimen and/or a checkpoint inhibitor (cpi), if eligible, and must have experienced disease progression following such therapy. participants should have received no more than 3 systemic lines of therapy in the recurrent or metastatic setting.

part e

participants with scchn must have experienced disease progression on or after their most recent systemic therapy. participants should have received no more than 1 or 2 systemic lines of therapy in the recurrent/metastatic setting as specified below. participants must have received a platinum-based regimen and a pd-(l)1 inhibitor.

parts d, f, and g

part d is closed to enrollment. part f and part g will enroll only participants with scchn.
participants with scchn must have received no previous systemic therapy in the recurrent or metastatic disease setting.

part d only

participants with nsclc must have histologically or cytologically documented squamous cell nsclc and must have received no previous systemic therapy for metastatic disease or radiation therapy to the lung that is > 30 gy within 6 months of the first dose of study treatment.
pd-l1 biomarker expression as determined by a pd-l1 ihc assay should be available

part f only

participants must have cps ≥1 by local pd-l1 ihc assay to be eligible for enrollment. participants must be able to submit a tissue sample for retrospective pd-l1 testing. tissue may be fresh biopsy or archival, collected within 2 years of cycle 1 day 1.

part g only

non-eu eligibility criteria: no cps requirement for the cohort evaluating tisotumab vedotin in combination with pembrolizumab and carboplatin.
eu-specific eligibility criteria: participants must have a cps ≥1 by local pd-l1 ihc assay.
participants must be able to submit a tissue sample for retrospective pd-l1 testing. tissue may be fresh biopsy or archival, collected within 2 years of cycle 1 day 1.
baseline measurable disease as measured by recist v1. 1.
eastern cooperative oncology group (ecog) performance status score of 0 or 1.

exclusion criteria:

participants with primary neuroendocrine or sarcomatoid histologies. for scchn, participants may not have a primary site of nasopharynx or salivary gland.
active bleeding conditions
ocular surface disease at the time of enrollment (note: cataract is not considered active ocular surface disease for this protocol)
other cancer: known past or current malignancy other than inclusion diagnosis.
uncontrolled tumor-related pain
inflammatory lung disease. participants with pulmonary disease are allowed if systemic steroids and long-term oxygen are not required
peripheral neuropathy greater than or equal to grade 2
active brain metastasis
part d, f, and g only: prior therapy with an anti-pd-1, anti-pd-l1, or anti-pd-l2 agent or with an agent directed to another stimulatory or co-inhibitory t-cell receptor.",1,0,1,0,0,0,18.0,200.0,Pleura,Other,0,0,All
160,160,160,896,NCT03486873,2023-11-08,long-term safety and efficacy extension study for participants with advanced tumors who are currently on treatment or in follow-up in a pembrolizumab (mk-3475) study (mk-3475-587/keynote-587),"a multicenter, open-label, phase 3 study to evaluate the long-term safety and efficacy in participants who are currently on treatment or in follow-up in studies that include pembrolizumab",,interventional,"the purpose of this study is to evaluate the long-term safety and efficacy of pembrolizumab (mk-3475) in participants from previous merck pembrolizumab-based parent studies who transition into this extension study.

this study will consist of three phases: 1) first course phase, 2) survival follow-up phase or 3) second course phase. each participant will transition to this extension study in one of the following three phases, depending on the study phase they were in at the completion of the parent study. participants who were in the first course phase of study treatment in their parent study will enter the first course phase of this study and complete up to 35 doses or more every 3 weeks (q3w) or 17 doses or more every 6 weeks (q6w) of study treatment with pembrolizumab or a pembrolizumab-based combination according to arm assignment. participants who were in the follow-up phase in the parent study (post-treatment or survival follow-up phase) will enter the survival follow-up phase of this study. participants who were in the second course phase in their parent study will enter second course phase of this study and complete up to 17 doses q3w or 8 doses q6w of study treatment with pembrolizumab or a pembrolizumab-based combination according to arm assignment.

any participant originating from a parent trial where crossover to pembrolizumab was permitted upon disease progression may be may be eligible for 35 doses as q3w or 17 doses q6w of pembrolizumab (approximately 2 years), if they progress while on the control arm and pembrolizumab is approved for the indication in the country where the potential eligible crossover participant is being evaluated.","inclusion criteria:

treated on the parent pembrolizumab studies established by the sponsor as mk-3475-587 ready
currently receiving pembrolizumab or in a follow-up phase

additional eligibility criteria for participants who enter second course phase once they are enrolled on mk-3475-587:

has not received any anticancer systemic treatment since the last dose of pembrolizumab or a pembrolizumab-based combination in first course phase
has an eastern cooperative oncology group (ecog) performance status of 0 or 1
demonstrates adequate organ function
have resolution of any toxic effect(s) of first course phase trial treatment with pembrolizumab or a pembrolizumab-based combination to grade 1 or less (except alopecia) before trial treatment in second course phase is started. if participant received major surgery or radiation therapy of >30 gray (gy), they must have recovered from the toxicity and/or complications of the intervention.
a female participant is eligible to enroll if she is not pregnant, not breastfeeding, and ≥1 of the following conditions applies: a woman of childbearing potential (wocbp) who agrees to use contraception during the study treatment period and for ≥120 days (corresponding to time needed to eliminate any study combination treatment(s) plus 30 days (a menstruation cycle) for study treatments with risk of genotoxicity.

exclusion criteria:

-there are no exclusion criteria to participate in mk-3475-587.

participants are excluded from entering second course trial treatment once they are enrolled on mk-3475-587 if any of the following criteria applies:

has severe hypersensitivity (≥ grade 3) to pembrolizumab and/or any of its excipients
has received a live vaccine within 30 days prior to the first dose of second course phase trial treatment
has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the cycle 1 day 1 of second course phase
has a known additional malignancy that is progressing or requires active treatment. exceptions include early stage cancers (carcinoma in situ or stage 1) treated with curative intent, melanoma (non-ulcerated, thin primary), basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy.
has known active central nervous system metastases and/or carcinomatous meningitis
has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., use of disease modifying agents, corticosteroids or immunosuppressive drugs). replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. note: participants that experienced pneumonitis during first course that did not meet the criteria for permanent discontinuation are eligible.
non-small cell lung cancer (nsclc) participants only: has interstitial lung disease
has an active infection requiring systemic therapy
has a known history of human immunodeficiency virus (hiv) infection.
has a known history of or is positive for hepatitis b or hepatitis c. for parent studies where inclusion of participants with hepatitis was permitted, mk-3475-587 will follow the parent study eligibility criteria for hepatitis.
is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the second course phase eligibility visit through 120 days after the last dose of study treatment.
has severe cardiovascular disease, i.e., arrhythmias, requiring chronic treatment, congestive heart failure (new york heart association class iii or iv) or symptomatic ischemic heart disease.
has hepatic decompensation (child-pugh score >6 [class b and c])
has uncontrolled thyroid dysfunction
has uncontrolled diabetes mellitus
has had an allogeneic tissue/solid organ transplant
has a known history of active tuberculosis (tb; bacillus tuberculosis)",1,0,0,1,0,0,18.0,200.0,Brain,Pleura,0,0,All
161,161,161,897,NCT03491540,2022-05-12,mechanical bowel preparation and oral antibiotics before rectal cancer surgery,mechanical bowel preparation and oral antibiotics before rectal cancer surgery: a multi center double-blinded randomized controlled trial (prepacol2 study),PREPACOL2,interventional,"this study aims to demonstrate that a preoperative combination of mechanical bowel preparation and oral antibiotics, before elective laparoscopic rectal cancer surgery, is associated with a reduction of postoperative surgical site infection rate, as compared to mechanical bowel preparation alone our hypothesis is that a preoperative colonic preparation including a combination of mechanical bowel preparation and oral antibiotics before elective laparoscopic rectal cancer surgery is associated with a reduced rate of 30-day postoperative surgical site infection, as compared to mechanical bowel preparation alone","inclusion criteria:

patients aged 18 or more
scheduled to undergo elective restorative laparoscopic cancer of the rectal (<15 cm from the anal margin) with sphincter preservation
with signed consent
and affiliated to the french social security system

exclusion criteria:

emergent surgery
scheduled total colo-proctectomy
scheduled abdominoperineal restion with definitive colostomy
scheduled associated concomitant resection of another organ (liver, etc.)
active bacterial infection at the time of surgery or recent antibiotic therapy (up to 15 days before surgery)
associated inflammatory bowel disease
patients with known colonization with multidrug-resistant enterobacteriacea
history of allergy or contraindication to the ornidazole, gentamycin, x-prep or to any of the excipients of the drugs used.
cirrhosis of grade b and c (child-pugh classification)
myasthenia
allergy to one of the other treatments administered for the purpose of the trial (including betadine)
patient suffering from severe central neurologic diseases, fixed or progressive.
pregnant patients
refusal to participate or inability to provide informed consent",1,0,0,1,0,0,18.0,200.0,Colon,Pleura,0,1,All
162,162,162,898,NCT03492528,2022-09-19,"cardiovascular outcome of cancer patients: the ""gmedico cohort""","cardiovascular outcome of cancer patients: the ""gmedico cohort""",GMEDICO,interventional,"the mediterranean group of cardio-oncology (gmedico) brings together french cardiologists and oncologists who have developed a protocol for the monitoring and cardio-oncological management of patients treated for cancer.

this unique organization makes it possible to envisage the creation of a large cohort from which the incidence and predictive factors of cardiovascular toxicity can be determined.

primary objective: to determine the cardiovascular prognosis of patients treated for cancer and followed up in cardio-oncology.

secondary objectives

to determine the clinical, biological and imaging factors associated with cardiovascular events under cancer treatment, in order to define a risk score including clinical, biological (biomarker) and imaging data.
to create a biological source for testing other biomarkers and conducting genome-wide association studies and genetic factors associated with cardiovascular events under cancer treatment.","inclusion criteria:

all adults referred for specialist cardio-oncology consultations before the initiation of a cancer treatment according to pre-established indications will be eligible.

exclusion criteria:

failure to provide information that makes it impossible to complete a consultation form or refuse to sign the consent.
minor or major patient under guardianship
pregnant or breastfeeding woman",1,0,0,0,0,1,18.0,200.0,Gastric,Gastric,0,0,All
163,163,163,901,NCT03496402,2023-10-24,"biological characterisation of high risk childhood cancer in children, adolescents and young adults (micchado)","molecular and immunological characterisation of high risk childhood cancer at diagnosis, treatment and follow-up - biological evaluation in children, adolescents and young adults -",MICCHADO,interventional,"methodology:

prospective, multicentric, open, non-randomised, non-therapeutic, interventional study","inclusion criteria:

inclusion within 3 months after diagnosis
availability of a cryopreserved tumour sample (primary and/or metastatic and/or lymph nodes) or peripheral blood or bone marrow samples (if invasion more than 30% of lymphoblasts) for leukaemias, obtained at the time of diagnosis during a routine procedure
availability of a formalin-fixed paraffin-embedded (ffpe) tumour sample (primary and/or metastasis and/or lymph nodes), obtained at the time of diagnosis during a routine procedure (except for leukaemia patients)
age: ≤ 25 years at diagnosis
written patient informed consent, or parents or legal representative written informed consent and assent of the child and the adolescent

compulsory affiliation to a social security scheme

additional inclusion criteria for the study:

to avoid multiple sampling for children, adolescents and young adults with cancer, patients already included or to be included in a study with similar analyses and/or objectives might also be included in micchado study and in this case, samples or data might be exchanged on a collaborative basis.

cohort 1:

high risk neuroblastoma:

- any type of neuroblastoma with mycn amplification, except inss stage 1

- stage 4 neuroblastoma in children older than one year at diagnosis

high risk rhabdomyosarcoma:

foxo1 rearrangement any stage;
and / or n1 ;
and / or metastatic rhabdomyosarcoma

high risk ewing sarcoma:

metastatic ewing sarcoma family of tumours (esft)
localised inoperable ewing sarcoma with primary tumours ≥ 200 ml

high risk osteosarcoma:

- metastatic osteosarcoma

- localised inoperable osteosarcoma

high risk leukaemia:

secondary acute myeloid leukaemia
biphenotypic acute leukaemia

cohort 2:

• extra cerebral or cerebral high risk tumours including:

other metastatic sarcomas,
other rare high risk cancers,
high risk renal tumours with surgery after an initial chemotherapy
rhabdoid brain tumours (at/rt) and extra cerebral rhabdoid tumours
high risk or metastatic cancers of unclear histological diagnosis • lymphoblastic leukaemia with high mrd at day 78 (time point 2) • very high risk t-cells acute lymphoblastic leukaemia:
mrd ≥ 10-2 at the end of the induction ;
or mrd ≥ 10-3 at day 78

cohort 3:

children, adolescents and young adults, with low/intermediate risk cancers belonging to the following types:

• neuroblastoma:

- localised, without mycn amplification

localised, inss stage 1, with mycn amplification

stage 4s, in infants (younger than one year at diagnosis), without mycn amplification

• rhabdomyosarcoma:

localised, without foxo1 rearrangement

• esft:

all non-high risk localised esft • osteosarcoma:
all non-high risk localised osteosarcoma

exclusion criteria:

main non-inclusion criteria common to all study cohorts:

1) age: patients > 25 years old at diagnosis 2) absence of patient or parents or legal representative written informed consent 3) patient for whom follow-up by the investigating centre does not appear feasible",1,0,0,0,0,1,1.0,25.0,Brain,Brain,0,0,All
164,164,164,907,NCT03503409,2023-01-02,idh1 (ag 120) inhibitor in patients with idh1 mutated myelodysplastic syndrome,a single-arm phase ii multicenter study of idh1 (ag 120) inhibitor in patients with idh1 mutated myelodysplastic syndrome,,interventional,patients with mds (myelodysplastic syndrome) and mutated idh1 patients will be treated with ag120 (idh1 inhibitor),"inclusion criteria:

patients must meet all of the following criteria to participate in the study:
age ≥ 18 years
myelodysplastic syndrome according to who classification including non-proliferative aml up to 29% of bm blast
belonging to one of the following categories :
higher risk (ipss high or int 2 ) mds without response to azacitidine (cr,pr, stable disease with hi) after at least 6 cycles , or relapsing after a response but without overt progression (defined by at least doubling of marrow blasts, compared to pre azacitidine bone marrow, or aml progression beyond 30% blasts)
untreated higher risk mds (ipss int-2, high) without life threatening cytopenia including anc <500/mm3 or any recent severe infections and /or platelets below 30,000/mm3 or any bleeding symptom
lower risk mds with resistance or loss of response to a previous treatment with epoetin alpha/ beta (≥60000 u/w) or darbopoetin (≥250 ug/w) given for at least 12 weeks and rbc transfusion requirement at least 2 u/8 weeks in the previous 16 weeks
presence of idh1 mutation in either blood or marrow prior to start of therapy;
normal renal function, defined by creatinine less than 1.5 times the upper limit of normal, creatinine clearance (modification of diet in renal disease) creatinine clearance ≥ 50 ml/min;
normal liver function, defined by total bilirubin and transaminases less than 1.5 times the upper limit of normal;
adequate cardiac ejection fraction (>40%);
patient is not known to be refractory to platelet transfusions;
written informed consent;
patient must understand and voluntarily sign consent form.
patient must be able to adhere to the visit schedule as outlined in the study and follow protocol requirements;
ecog performance status 0-2 at the time of screening;
female subjects with reproductive potential must have a negative serum pregnancy test within 7 days prior to the start of therapy. subjects with reproductive potential are defined as sexually mature women who have not undergone a hysterectomy, bilateral oophorectomy or tubal occlusion or who have not been naturally postmenopausal (i.e., who have not menstruated at all) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months). females of reproductive potential as well as fertile men and their partners who are female of reproductive potential must agree to abstain from sexual intercourse or to use two highly effective forms of contraception from the time of giving informed consent, during the study and for 3 months (females and males) following the last dose of ag-120. a highly effective form of contraception is defined as hormonal oral contraceptives, injectables, patches, intrauterine devices.

male patients must :

agree the need for the use of a condom if engaged in sexual activity with a woman of childbearing potential during the entire period of treatment, even if disruption of treatment and during 3 months after end of treatment.
agree to learn about the procedures for preservation of sperm before starting treatment

exclusion criteria:

a patient meeting any of the following criteria is not eligible to participate in the study:
severe infection or any other uncontrolled severe condition.
significant cardiac disease - nyha class iii or iv or having suffered a myocardial infarction in the last 6 months.
less than 14 days since prior treatment with growth factors (epo, g-csf).
use of investigational agents within 30 days or any anticancer therapy within 2 weeks before the study entry with the exception of hydroxyurea. the patient must have recovered from all acute toxicity from any previous therapy.
subject has a heart-rate corrected qt interval using fridericia's method (qtcf) ≥ 470 msec or any other factor that increases the risk of qt prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long qt interval syndrome). subjects with prolonged qtcf interval in the setting of bundle branch block may participate in the study.
subject is taking known strong cytochrome p450 (cyp) 3a4 inducers or inhibitors or sensitive cyp3a4 substrate medications with a narrow therapeutic window, unless they can be transferred to other medications within ≥ 5 half-lives prior to dosing.
subject is taking p-glycoprotein (p-gp) transporter-sensitive substrate medications with a narrow therapeutic window, unless they can be transferred to other medications within ≥ 5 half-lives prior to administration of study treatment
active cancer or cancer during the year prior to trial entry other than basal cell carcinoma, or carcinoma in situ of the cervix or breast.
patient already enrolled in another therapeutic trial of an investigational drug.
known hiv infection or active hepatitis b or c.
women who are or could become pregnant or who are currently breastfeeding.
any medical or psychiatric contraindication that would prevent the patient from understanding and signing the informed consent form.
patient eligible for allogeneic stem cell transplantation.
known allergies to ag 120 or any of its excipients.
the study does not provide for the inclusion of persons referred to in articles l. 1121-5 to l. 1121-9 and l. 1122-1-2 of the public health code (e.g. minors, protected adults, etc.)
no affiliation to a health insurance system.",1,0,1,0,0,0,18.0,200.0,Brain,Pleura,0,0,All
165,165,165,909,NCT03505320,2023-10-31,"a study to assess the antitumor activity, safety, pharmacokinetics and biomarkers of zolbetuximab (imab362) in participants with claudin (cldn) 18.2 positive, metastatic or advanced unresectable gastric and gastroesophageal junction (gej) adenocarcinoma","a phase 2 study of zolbetuximab (imab362) as monotherapy, in combination with mfolfox6 (with or without nivolumab) and in combination with pembrolizumab in subjects with metastatic or locally advanced unresectable gastric or gastroesophageal junction (gej) adenocarcinoma whose tumors have high or intermediate claudin (cldn) 18.2 expression",ILUSTRO,interventional,"the purpose of this study is to determine the objective response rate (orr) of zolbetuzimab as a single agent as assessed by an independent central reader. this study will also assess the orr and progression free survival (pfs) of zolbetuximab in combination with mfolfox6 (with or without nivolumab) and in combination with pembrolizumab, assess the safety and tolerability, assess the effects on cldn18.2 expression and assess the immunogenicity and immunomodulatory effects of zolbetuximab as a single agent and in combination with mfolfox6 (with or without nivolumab) and in combination with pembrolizumab. this study will also evaluate the pharmacokinetics (pk) of zolbetuximab, oxaliplatin, fluorouracil (5-fu), and pembrolizumab, evaluate health-related quality of life (hrqol), evaluate the disease control rate (dcr), duration of response (dor), pfs of zolbetuximab as a single agent, in combination with mfolfox6 (with or without nivolumab) and in combination with pembrolizumab based on both investigator and independent central reader assessment, assess overall survival (os) of zolbetuximab as a single agent and in combination with pembrolizumab.","inclusion criteria:

female subject eligible to participate if she is not pregnant and at least one of the following conditions applies:

not a woman of child-bearing potential (wocbp) or
wocbp who agrees to follow the contraceptive guidance throughout the treatment period and for at least 9 months after the final oxaliplatin administration and 6 months after the final administration of all other study drugs.
female subject must agree not to breastfeed starting at screening and throughout the study period, and for 6 months after the final study drug administration.
female subject must agree not to donate ova starting at screening and throughout the study period, and for 9 months after the final oxaliplatin administration and 6 months after the final administration of all other study drugs.
a sexually active male subject with a female partner(s) who is of child-bearing potential must agree to use contraception during the treatment period and for at least 6 months after the final study drug administration.
male subject must agree not to donate sperm starting at screening and throughout the study period, and for 6 months after the final study drug administration.
male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period and for 6 months after the final study drug administration.
subject has histologically confirmed gastric or gej adenocarcinoma.
subject has radiographically-confirmed, locally advanced, unresectable or metastatic disease within 28 days prior to the first dose of study treatment.
subject's tumor is positive for cldn18.2 expression.
subject agrees to not participate in another interventional study while on treatment.
subject has ecog performance status 0 to 1.
subject has predicted life expectancy ≥ 12 weeks.

subject must meet all of the following criteria based on the centrally or locally analyzed laboratory tests collected within 14 days prior to the first dose of study treatment. in case of multiple central laboratory data within this period, the most recent data should be used.

hemoglobin (hgb) ≥ 9 g/dl (transfusion is allowed, but post-transfusion hgb [24 hours or later following transfusion] must be ≥ 9 g/dl)
absolute neutrophil count (anc) ≥ 1.5 × 109/l
platelets ≥ 100 × 10^9/l
albumin ≥ 2.5 g/dl
total bilirubin ≤ 1.5 × upper limit of normal (uln)
aspartate aminotransferase (ast) and alanine aminotransferase (alt) ≤ 2.5 × uln in subjects without liver metastases (≤ 5 × uln if liver metastases are present)
estimated creatinine clearance ≥ 30 ml/min
prothrombin time/international normalized ratio and partial thromboplastin time ≤ 1.5 × uln (except for subjects receiving anticoagulation therapy)

specific to cohort 1a:

subject has measurable disease according to recist 1.1 within 28 days prior to the first dose of study treatment per investigator assessment. for subjects with only 1 evaluable lesion and prior radiotherapy ≤ 3 months before enrollment, the lesion must either be outside the field of prior radiotherapy or must have documented progression following radiation therapy.
subject has disease progression on or after at least 2 prior regimens for their advanced disease, including fluoropyrimidine and platinum-containing chemotherapy, and if appropriate, her2/neu-targeted therapy and all associated side effects have resolved to grade 1 or less.
subject must have an additional available tumor specimen collected within 3 months prior to the first dose of study treatment.
subject must be an appropriate candidate for a tumor biopsy and is amenable to undergo a tumor biopsy during the screening period (if applicable) and treatment period as indicated in the schedule of assessments.

specific to cohort 2:

subject has measurable disease according to recist 1.1 within 28 days prior to the first dose of study treatment per investigator assessment. for subjects with only 1 evaluable lesion and prior radiotherapy ≤ 3 months before enrollment, the lesion must either be outside the field of prior radiotherapy or must have documented progression following radiation therapy.
subject has not received prior systemic anti-cancer therapy for their advanced disease (subject may have received neoadjuvant and/or fluorouracil-containing adjuvant chemotherapy as long as it has been completed ≥ 6 months before the first dose of study treatment).
subject has a gastric or gej tumor that is her2-negative as determined by local or central testing.
subject must have an additional available tumor specimen collected within 3 months prior to the first dose of study treatment.
subject must be an appropriate candidate for a tumor biopsy and is amenable to undergo a tumor biopsy during the screening period (if applicable) and treatment period as indicated in the schedule of assessments.

specific to cohort 3a:

subject has radiologically evaluable disease (measurable and/or non-measurable) according to recist 1.1, per local assessment, ≤ 28 days prior to the first dose of study treatment. for subjects with only 1 evaluable lesion and prior radiotherapy ≤ 3 months before enrollment, the lesion must either be outside the field of prior radiotherapy or must have documented progression following radiation therapy.
subject has disease progression on or after at least 2 prior regimens for their advanced disease, including fluoropyrimidine and platinum-containing chemotherapy, and if appropriate, her2/neu-targeted therapy.
subject has not received prior checkpoint inhibitor therapy.

specific to cohort 4a and 4b:

subject has radiologically evaluable disease.
subject has not received prior systemic anti-cancer therapy for their advanced disease.
subject has a gastric or gej tumor that is her2-negative as determined by local or central testing.
subject has not received prior checkpoint inhibitor therapy.

specific to cohort 4b only:

subject must have an additional available tumor specimen collected within 3 months prior to the first dose of study treatment.
subject must be an appropriate candidate for a tumor biopsy and is amenable to undergo a tumor biopsy during the screening period (if applicable) and treatment period.
subject has a tumor that is pd-l1 positive.

exclusion criteria:

subject has had prior severe allergic reaction or intolerance to known ingredients of zolbetuximab or other monoclonal antibodies, including humanized or chimeric antibodies.
subject has known immediate or delayed hypersensitivity or contraindication to any component of study treatment.
subject has received other investigational agents or devices concurrently or within 28 days prior to first dose of study treatment.
subject has received systemic immunosuppressive therapy, including systemic corticosteroids 14 days prior to first dose of study treatment.
subject has a complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent recurrent vomiting.
subject has significant gastric bleeding and/or untreated gastric ulcers that would preclude the subject from participation.
subject has history of central nervous system metastases and/or carcinomatous meningitis from gastric/gej cancer.
subject has a known history of a positive test for human immunodeficiency virus (hiv) infection or known active hepatitis b (positive hepatitis b surface antigen [hbsag]) or hepatitis c infection.
subject has had within 6 months prior to first dose of study treatment any of the following: unstable angina, myocardial infarction, ventricular arrhythmia requiring intervention or hospitalization for heart failure.
subject has active infection requiring systemic therapy that has not completely resolved within 7 days prior to the start of study treatment.
subject has active autoimmune disease that has required systemic treatment within the past 3 months prior to the start of study treatment.
subject has a clinically significant disease or co-morbidity that may adversely affect the safe delivery of treatment within this study or make the subject unsuitable for study participation.
subject has psychiatric illness or social situations that would preclude study compliance.
subject has had a major surgical procedure ≤ 28 days before start of study treatment.

subject is without complete recovery from a major surgical procedure ≤ 14 days before start of study treatment

subject has received radiotherapy for locally advanced unresectable or metastatic gastric or gej adenocarcinoma ≤ 14 days (cohorts 1 and 3a) and ≤ 28 days (cohorts 2 and 4a or 4b) prior to start of study treatment and has not recovered from any related toxicity.
subject has another malignancy, for which treatment is required.

cohort 2 and 4 only, subject has any of the following:

prior severe allergic reaction or intolerance to any component of mfolfox6 chemotherapeutics in this study
known dihydropyrimidine dehydrogenase deficiency (dpd).
known peripheral neuropathy > grade 1 (absence of deep tendon reflexes as the sole neurological abnormality does not render the subject ineligible).
sinusoidal obstruction syndrome, formerly known as veno-occlusive disease, if present, should be stable or improving.
history of clinically significant ventricular arrhythmias.
qtc interval > 450 msec for male subjects; qtc interval > 470 msec for female subjects.
history or family history of congenital long qt syndrome.
cardiac arrhythmias requiring anti-arrhythmic medications (subjects with rate controlled atrial fibrillation for > 1 month prior to first dose of study treatment are eligible).

cohorts 3a, 4a and 4b only, subject has any of the following:

subjects with ongoing or previous autoimmune disease or interstitial lung disease, active diverticulitis or gastrointestinal ulcerative disease, or solid organ or stem cell transplant (for cohort 4) or other uncontrolled or clinically significant medical disorders.
subjects with type 1 diabetes mellitus, endocrinopathies stably maintained on appropriate replacement therapy or skin disorders (e.g., vitiligo, psoriasis, or alopecia) not requiring systemic treatment are allowed.
subject has known history of serious hypersensitivity reaction to a known ingredient of pembrolizumab or nivolumab.
cohort 4b only: subject with known microsatellite instability-high or mismatch repair deficient tumors.",1,0,1,0,0,0,18.0,200.0,Gastric,Gastric,0,0,All
166,166,166,912,NCT03514368,2023-03-29,monitoring of immunological mechanisms and biomarkers underlying efficacy and toxicity of cancer immunotherapy,monitoring of immunological mechanisms and biomarkers underlying efficacy and toxicity of cancer immunotherapy,MINER,interventional,"this trial is a translational, open-label, multi-site, prospective cohort study of 520 patients aiming to identify and to monitor immunological biomarkers associated with therapeutic response to immune checkpoints blockade (icb), in patients with multiple types of advanced (unresectable and/or metastatic) solid cancers.

the study will be conducted on a population of patients receiving icb (anti-pd-1 or anti-pd-l1 or anti-ctla4, alone or in combination) in the context of either routine care or a clinical study protocol.

patients with any of the following tumor types may be enrolled in the trial:

non-small cell lung cancer (nsclc),
head and neck cancer,
melanoma,
bladder cancer,
other tumor types when immuno-oncology agent is expected to be efficient or when a clinical trial is an option.

for each included patient, tumor biopsy specimens and blood samples will be collected at different time points.

all included patients will be followed-up until progression. after this date, survival data will be collected.","inclusion criteria:

age ≥18 years at the time of study entry.
patient with histologically documented metastatic and/or unresectable solid malignant tumor (nsclc, head and neck, melanoma (except uveal melanoma), bladder cancer or any other advanced solid tumor when i-o agent is expected to be efficient or when a clinical trial is an option).
patient for which a treatment with immune checkpoint blockade including, but not limited to, anti-pd-1, anti-pd-l1 and anti-ctla-4 mab alone or in combination has been decided.
archived tumor specimen available or feasible for pre-treatment tumor biopsy.
current treatment with icb not yet started.
evaluable disease (measurable as per recist 1.1. or not).
ecog performance status 0-2.
patient able to participate and willing to give informed consent prior to performance of any study-related procedures.
patient affiliated to a social health insurance in france.

exclusion criteria:

patient pregnant, or breast-feeding.
uveal melanoma
any condition contraindicated with tumor /blood sampling procedures required by the protocol.
known history of positive test for hepatitis b virus or hepatitis c virus or human immunodeficiency virus (hiv) or known acquired immunodeficiency syndrome (aids).
any current severe or uncontrolled disease, including, but not limited to ongoing or active infection and auto immune disorders.
any psychological, familial, geographic or social situation, according to the judgment of investigator, potentially preventing the provision of informed consent or compliance to study procedure.
patient who has forfeited his/her freedom by administrative or legal award or who is under guardianship.",1,0,0,0,0,1,18.0,200.0,Pleura,Pleura,0,0,All
167,167,167,913,NCT03515798,2020-06-30,study of immunotherapy in combination with chemotherapy in her2-negative inflammatory breast cancer,"a prospective multicenter open-label, randomized phase ii study of pembrolizumab in combination with neoadjuvant ec-paclitaxel regimen in her2-negative inflammatory breast cancer.",PELICAN,interventional,this phase ii multicentre randomized open-label study will assess the safety and efficacy of pembrolizumab in combination with standard chemotherapy in inflammatory breast cancer. pembrolizumab will be administered every 3 weeks during the neoadjuvant chemotherapy. tissue and blood samples will be collected pre- and post-treatment for translational research.,"inclusion criteria:

male/female participants who are at least 18 years of age on the day of signing informed consent
have an eastern cooperative oncology group (ecog) performance status of 0 to 1 evaluation of ecog is to be performed within 7 days prior to the date of randomization. note: may consider ecog ps 2 if good rationale provided and discussed with sponsor team.
able to comply with the protocol,
patient affiliated to the national ""social security"" regimen or beneficiary of this regimen, or any other regimen of social security
patient (or legally acceptable representative if applicable) has provided written informed consent for the trial,

previously untreated, histologically confirmed diagnosis of breast cancer and confirmed inflammatory breast cancer defined as follows:

- t4d any n following american joint committee on cancer (ajcc)-8th version classification: breast erythema, edema and/or peau d'orange, occupying at least 1/3 of the breast, with or without underlying palpable mass, duration of history of no more than 6 months.

her2 negative tumors by immunohistochemistry (ihc 0 or 1+) or fluorescent/chromogenic in situ hybridization (fish- or cish-)
hormone receptors status known,
no metastases,
have adequate organ function. specimens must be collected within 10 days prior to the start of study treatment.
adequate hematologic function: absolute neutrophil count ≥ 1.5 x 109/l and platelets ≥ 100 x 109 and hb ≥ 9.0 g/dl or ≥5.6 mmol/l, criteria must be met without erythropoietin dependency and without packed red blood cell (prbc) transfusion within last 2 weeks.
adequate liver function: total bilirubin ≤1.5 ×uln or direct bilirubin ≤uln for participants with total bilirubin levels >1.5 × uln and - asat ≤ 2.5 uln and alat ≤ 2.5 uln,
adequate kidney function: serum creatinine ≤ 1.5 uln or creatinine clearance ≥ 30 ml/min for participant with creatinine levels >1.5 × institutional uln, creatinine clearance (crcl) should be calculated per institutional standard.
international normalized ratio (inr) or prothrombin time (pt) ≤ 1.5 uln unless subject is receiving anticoagulant therapy, as long as pt or tca is within therapeutic range of intended use of the anticoagulants,
adequate cardiac function: left ventricular ejection fraction (lvef) ≥ 50% (isotopic or ultrasound methods),

a female participant is eligible to participate if she is not pregnant (see appendix 3), not breastfeeding, and at least one of the following conditions applies:

not a woman of childbearing potential (wocbp) as defined in appendix 3 or
a wocbp who agrees to follow the contraceptive guidance in appendix 3 during the treatment period and for at least 12 months after the last dose of cyclophosphamide and 4 months after the last dose of pembrolizumab, whichever come last.

note: abstinence is acceptable if this is the established and preferred contraception for the subject

a male participant must agree to use a contraception as detailed in appendix 3 of this protocol during the treatment period and for at least 6 months after the last dose of study treatment and refrain from donating sperm during this period (corresponding to time needed to eliminate any study treatments plus an additional 120 days (a spermatogenesis cycle) for study treatments with risk of genotoxicity at any dose).

exclusion criteria:

has metastatic breast cancer,
has her2-positive breast cancer,
has bilateral breast cancer
prior allogeneic stem cell or solid organ transplantation
a wocbp who has a positive serum pregnancy test within 72 hours prior to randomiza-tion
is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment, note: participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
has known active cns disease or carcinomatous meningitis.
has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug,
has a known history of active tb (bacillus tuberculosis),
has severe hypersensitivity (≥grade 3) to pembrolizumab and/or any of its excipients,
if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy,
has a known additional malignancy that is progressing or has required active treatment within the past 3 years. note: participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment,
has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis,
has an active infection requiring systemic therapy.
has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator,
has known psychiatric or substance abuse disorders that would interfere with coopera-tion with the requirements of the trial,
is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment,
has received prior therapy with an anti-pd-1, anti-pd-l1, or anti pd l2 agent or with an agent directed to another stimulatory or co-inhibitory t-cell receptor (e.g., ctla-4, ox 40, cd137).,
has a known history of human immunodeficiency virus (hiv) (hiv 1/2 antibodies),
has known history of hepatitis b (e.g., hbsag reactive) or known active hepatitis c virus infection (e.g., hcv rna [qualitative] is detected)
has received a live vaccine within 30 days prior to the first dose of study drug. examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, bacillus calmette-guérin (bcg), and typhoid vaccine. seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., flumist®) are live attenuated vaccines and are not allowed.",1,0,1,0,0,0,18.0,200.0,Breast,Breast,0,0,All
168,168,168,921,NCT03520075,2023-08-03,study of astx029 in subjects with advanced solid tumors,"a phase 1-2 study of the safety, pharmacokinetics, and activity of astx029 in subjects with advanced solid tumors",,interventional,"this study is a first-in-human, open-label, multicenter, phase 1-2 study to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of astx029 administered orally to subjects with advanced solid malignancies who are not candidates for approved or available therapies.","inclusion criteria:

subjects must fulfill all of the following inclusion criteria.

able to understand and comply with study procedures, understand the risks involved in the study, and provide written informed consent before any study-specific procedure is performed.
men or women 18 years of age or older.
subjects with histologically or cytologically confirmed advanced solid tumors that are metastatic or unresectable, who are refractory or have relapsed after treatment with available therapies or for whom standard life-prolonging measures or approved therapies are not available. in phase 1 part b and in the phase 2 portion of the protocol, subjects must also have documented gene alterations in the mapk pathway as detailed in the protocol.
in phase 1 part b of the protocol, subjects must have disease lesions that are amenable to biopsy.
in the phase 2 portion of the protocol, subjects must have measurable disease according to recist v1.1.
eastern cooperative oncology group performance status 0 to 2.

acceptable organ function as evidenced by the following laboratory data:

aspartate aminotransferase (ast) and alanine aminotransferase ≤2×upper limit of normal (uln) or ≤3 uln in the presence of liver metastases.
total serum bilirubin ≤1.5×uln.
absolute neutrophil count (anc) ≥1500 cells/mm3.
platelet count ≥100,000 cells/mm3.
calculated creatinine clearance (by the standard cockcroft gault formula) of ≥50 ml/min or glomerular filtration rate of ≥50 ml/min.
women of child-bearing potential (according to recommendations of the clinical trial facilitation group [ctfg]; see protocol for details) must not be pregnant or breastfeeding and must have a negative pregnancy test within 24 hours before the first dose of study treatment. while receiving study treatment and for at least 5 half-lives of astx029 or metabolite plus 30 days after completing treatment, women of child-bearing potential must agree to practice highly effective contraceptive measures (as described in the protocol) and must refrain from donating eggs (ova, oocytes) for the purpose of reproduction.
men with female partners of child-bearing potential (according to recommendations of the ctfg; see protocol for details) must agree to, during the treatment period and for at least 5 half-lives of astx029 or metabolite plus 90 days after completing treatment, practice highly effective contraceptive measures (as described in the protocol), not to father a child, and to refrain from donating sperm.

exclusion criteria:

hypersensitivity to astx029 or excipients of the drug product.
poor medical risk in the investigator's opinion because of systemic diseases in addition to the cancer under study, for example, uncontrolled infections.
life-threatening illness, significant organ system dysfunction, or other condition that, in the investigator's opinion, could compromise subject safety or the integrity of study outcomes or interfere with the absorption or metabolism of astx029.

prior anticancer treatments or therapies within the indicated time window prior to first dose of study treatment (astx029), as follows:

cytotoxic chemotherapy or radiotherapy within 3 weeks prior. palliative radiotherapy to a single lesion within 2 weeks prior. any encountered treatment-related toxicities (excepting alopecia) not stabilized or resolved to ≤grade 1.
monoclonal antibodies within 4 weeks prior. any encountered treatment-related toxicities not stabilized or resolved to ≤grade 1.
molecularly targeted drug or investigational drugs, without the potential for delayed toxicity, within 4 weeks of the first dose of study treatment or 5 half-lives (minimum 14 days), whichever is shorter. any encountered treatment-related toxicities (excepting alopecia) not stabilized or resolved to ≤grade 1.
prior treatment with extracellular signal-regulated kinase (erk) inhibitors.

history of, or at risk for, cardiac disease, as evidenced by 1 or more of the following conditions:

abnormal left ventricular ejection fraction (lvef; <50%) on echocardiogram (echo) or multiple-gated acquisition (muga) scan.
congestive cardiac failure of ≥grade 3 severity according to new york heart association functional classification defined as patients with marked limitation of activity and who are comfortable only at rest.
unstable cardiac disease including unstable angina or hypertension as defined by the need for overnight hospital admission within the last 3 months (90 days).
history or evidence of long qt interval corrected for heart rate (qtc), ventricular arrhythmias including ventricular bigeminy, complete left bundle branch block, clinically significant bradyarrhythmias such as sick sinus syndrome, second- and third-degree atrioventricular (av) block, presence of cardiac pacemaker or defibrillator, or other significant arrhythmias.
screening 12-lead electrocardiogram (ecg) with measurable qtc interval of ≥470 msec. (fridericia's formula should be used to calculate the qtc interval throughout the study.)
known history of human immunodeficiency virus (hiv) infection or seropositive results consistent with active hepatitis b virus (hbv) or active hepatitis c virus (hcv) infection.
known brain metastases, unless previously treated and stable for at least 3 months with or without steroids.
known significant mental illness or other conditions, such as active alcohol or other substance abuse that, in the opinion of the investigator, predispose the subject to high risk of noncompliance with the protocol treatment or assessments.

history or current evidence/risk of retinal vein occlusion (rvo) or central serous retinopathy (csr) including:

presence of predisposing factors to rvo or csr (eg, uncontrolled glaucoma or ocular hypertension, uncontrolled diabetes mellitus) or

visible retinal pathology as assessed by ophthalmic examination at screening that is considered a risk factor for rvo or csr such as:

evidence of optic disc cupping or
evidence of new visual field defects on automated perimetry or
intraocular pressure >21 mmhg as measured by tonography.",1,1,1,0,0,0,18.0,200.0,Pleura,Pleura,0,0,All
169,169,169,924,NCT03524430,2023-08-09,rna disruption assay (rda)-breast cancer response evaluation for individualized therapy,rna disruption assay (rda)-breast cancer response evaluation for individualized therapy (brevity / brevity-02 in germany),BREVITY,interventional,the current study aims to provide validation results of rna disruption assay (rda) as a tumour response assessment tool that uses tumour core biopsies taken starting from 35 +/- 4 days after the initiation of neoadjuvant chemotherapy.,"inclusion criteria

women aged at least 18 years;
patients must be able to provide informed consent and sign the informed consent form to participate in the rda study before any study procedures starts;
newly diagnosed clinical stage i, ii or iii breast cancer with complete surgical excision of the breast cancer after neoadjuvant therapy as the treatment goal;
tumour size at least 1 cm in one dimension by clinical or radiographic exam (who criteria);
must have histological confirmation of invasive breast cancer of any subtype or grade;
patient is scheduled for neoadjuvant chemotherapy +/- antibodies and +/- other drugs according to standard of care;
patient willing to have 2 research core needle biopsies (for rda) taken at 2 collection timepoints during neoadjuvant chemotherapy treatment.

exclusion criteria

patient who has had prior local (i.e. surgery or radiotherapy) or systemic (i.e. endocrine or cytotoxic) therapy for the current breast cancer;
participation in another interventional clinical trial with concurrent treatment with experimental drugs to treat the current breast cancer during the period of neoadjuvant therapy (from diagnosis until surgery);
stage iv breast cancer;
bilateral or multicentric breast tumour;
prior malignant disease except curatively treated in-situ maligancies;
concurrent pregnancy;
breast feeding woman;
concurrent medical, psychiatric or addictive disorders that may limit the ability to give informed consent or complete the trial;
reasons indicating risk of poor compliance with study procedures;
patient not able to consent;",1,0,0,0,0,1,18.0,200.0,Breast,Breast,0,1,Female
170,170,170,926,NCT03526835,2023-02-15,a study of bispecific antibody mcla-158 in patients with advanced solid tumors,phase 1/2 dose escalation and cohort expansion study evaluating single-agent mcla-158 in metastatic colorectal cancer and other advanced solid tumors,,interventional,"this is a phase 1/2 open-label, multi-center, multi-national study with an initial dose escalation part to determine the rp2d of mcla-158 single agent in patients with mcrc.

the dose escalation part has been completed and the rp2d will be further evaluated in an expansion part of the study. cohorts of selected solid tumor indications for which there is evidence of egfr dependency and potential sensitivity to egfr inhibition will be evaluated.

the study will further assess the safety, tolerability, pk, pd, immunogenicity, and anti-tumor activity of mcla-158.","inclusion criteria:

histologically or cytologically confirmed solid tumors with evidence of metastatic or locally advanced disease not amenable to standard therapy with curative intent.

hnscc patients - gastric/gastroesophageal junction adenocarcinoma with histologically confirmed egfr amplification (fish score egfr/cep7 ratio ≥2.0, or ngs egfr copy ≥8, or cfdna >2.14, or egfr ihc h-score ≥200) - nsclc scc patients

a baseline fresh tumor sample (ffpe) from a metastatic or primary site.
amenable for biopsy.
measurable disease as defined by recist version 1.1 by radiologic methods.
eastern cooperative oncology group (ecog) performance status of 0 or 1.
life expectancy ≥ 12 weeks, as per investigator.
left ventricular ejection fraction (lvef) ≥ 50% by echocardiogram (echo) or multiple gated acquisition scan (muga).
adequate organ function

exclusion criteria:

central nervous system metastases that are untreated or symptomatic, or require radiation, surgery, or continued steroid therapy to control symptoms within 14 days of study entry.
known leptomeningeal involvement.
participation in another clinical trial or treatment with any investigational drug within 4 weeks prior to study entry.
any systemic anticancer therapy within 4 weeks or 5 half-lives whichever is longer of the first dose of study treatment. for cytotoxic agents that have major delayed toxicity ( e.g. mitomycin c,nitrosoureas), or anticancer immunotherapies, a washout period of 6 weeks is required.
requirement for immunosuppressive medication (e.g. methotrexate, cyclophosphamide)
major surgery or radiotherapy within 3 weeks of the first dose of study treatment. patients who received prior radiotherapy to ≥25% of bone marrow are not eligible, irrespective of when it was received.
persistent grade >1 clinically significant toxicities related to prior antineoplastic therapies (except for alopecia); stable sensory neuropathy ≤ grade 2 nci-ctcae v4.03 is allowed.
history of hypersensitivity reaction or any toxicity attributed to human proteins or any of the excipients that warranted permanent cessation of these agents.
uncontrolled hypertension (systolic > 150 mmhg and/or diastolic > 100 mmhg) with appropriate treatment or unstable angina.
history of congestive heart failure of class ii-iv new york heart association (nyha) criteria, or serious cardiac arrhythmia requiring treatment (except atrial fibrillation, paroxysmal supraventricular tachycardia).
history of myocardial infarction within 6 months of study entry.
history of prior malignancies with the exception of excised cervical intraepithelial neoplasia or nonmelanoma skin cancer, or curatively treated cancer deemed at low risk for recurrence with no evidence of disease for at least 3 years.
current dyspnea at rest of any origin, or other diseases requiring continuous oxygen therapy.
patients with a history of interstitial lung disease (e.g.: pneumonitis or pulmonary fibrosis) or evidence of ild on baseline chest ct scan.
current serious illness or medical conditions including, but not limited to uncontrolled active infection,clinically significant pulmonary, metabolic or psychiatric disorders.
patients with the following infectious diseases:

active hepatitis b infection (hbsag positive) without receiving antiviral treatment. note: patients with active hepatitis b (hbsag positive) must receive antiviral treatment with lamivudine, tenofovir, entecavir, or other antiviral agents, starting at least ≥7 days before the initiation of the study treatment. patients with antecedents of hepatitis b (anti-hbc positive, hbsag and hbv-dna negative) are eligible.

positive test for hepatitis c ribonucleic acid (hcv rna). note: patients in whom hcv infection resolved spontaneously (positive hcv antibodies without detectable hcv-rna) or who achieved a sustained response after antiviral treatment and show absence of detectable hcv rna ≥6 months (with the use of ifn-free regimens) or ≥ 12 months (with t the use of ifn-based regimens) after cessation of antiviral treatment are eligible.

patients with current cirrhotic status of child-pugh class b or c; known fibrolamellar hcc, sarcomatoid hcc, or mixed cholangiocarcinoma and hcc.
pregnant or lactating women; patients of childbearing potential must use highly effective contraception methods prior to study entry, for the duration of study participation, and for 6 months after the last dose of mcla-158.",1,1,1,0,0,0,18.0,200.0,Pleura,Colon,0,0,All
171,171,171,930,NCT03530397,2023-10-17,a study to evaluate medi5752 in subjects with advanced solid tumors,"a phase 1, open-label, dose-escalation and dose-expansion study to evaluate the safety, tolerability pharmacokinetics immunogenicity, and antitumor activity of medi5752 in subjects with advanced solid tumors.",,interventional,"the purpose of this study is to evaluate medi5752 and carboplatin and pemetrexed or paclitaxel or nab-paclitaxel in adult subjects with advanced solid tumors, when administered as a single agent or combined with chemotherapy.","inclusion criteria

age ≥ 18 years at the time of screening
world health organization/eastern cooperative oncology group (ecog) performance status of 0 or 1 at enrollment
life expectancy ≥ 12 weeks
histologically or cytologically-confirmed advanced solid tumors
subjects who have received prior anti-pd-1, anti-pd-l1, or anti-ctla-4 therapy or any concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal therapy for cancer treatment may be eligible to enter the study following a washout period as applicable
females of childbearing potential who are sexually active with a nonsterilized male partner must use at least one highly effective method of contraception
nonsterilized males who are sexually active with a female partner of childbearing potential must use a male condom with spermicide where locally available from day 1 and for 90 days after the final dose of investigational product. males receiving pemetrexed or carboplatin must use contraception during study treatment and up to 6 months thereafter.
subjects must have at least one measurable lesion
adequate organ and marrow function
written informed consent and any locally required authorization
subjects must provide tumor material as applicable

exclusion criteria

involvement in the planning and/or conduct of the study (applies to both medimmune staff and/or staff at the study site)
concurrent enrollment in another clinical study, unless it is an observational clinical study or the follow-up period of an interventional study

for subjects who have received prior anti-pd-1, anti-pd-l1, or anti-ctla-4:

subjects must not have received anti-pd-1, anti-pd-l1, anti-ctla-4 or any other immunotherapy or immune-oncology (io) agent within 21 days of commencing treatment with investigational product.
subject must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
all aes while receiving prior immunotherapy must have completely resolved or resolved to grade 1 prior to screening for this study.
current or prior use of immunosuppressive medication within 14 days before the first dose of investigational product is excluded.
receipt of live attenuated vaccine within 30 days prior to the first dose of investigational product.
active or prior documented autoimmune or inflammatory disorders
history of active primary immunodeficiency:
history of organ transplant
known allergy or reaction to any component of the planned study treatment.
untreated cns metastatic disease, leptomeningeal disease, or cord compression
unresolved toxicities from prior anticancer therapy, defined as having not resolved to nci ctcae v4.03 grade 0 or 1, or to levels dictated in the inclusion/exclusion criteria
major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of investigational product or still recovering from prior surgery
female subjects who are pregnant or breastfeeding, as well as male or female subjects of reproductive potential who are not willing to employ one highly effective method of birth control
uncontrolled intercurrent illness, that would limit compliance with study requirement, substantially increase risk of incurring aes or compromise the ability of the subject to give written informed consent.
any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of the subject's safety or study results
judgment by the investigator that the subject is unsuitable to participate in the study and the subject is unlikely to comply with study procedures, restrictions, and requirements.",1,1,0,0,0,0,18.0,120.0,Pleura,Pleura,1,0,All
172,172,172,931,NCT03531099,2021-11-19,"phase 3, multicenter, randomized study, evaluating the efficacy and tolerability of focused hifu (high intensity focused ultrasound) therapy compared to active surveillance in patients with significant low risk prostate cancer","phase 3, multicenter, randomized study, evaluating the efficacy and tolerability of focused hifu therapy compared to active surveillance in patients with significant low risk prostate cancer",HIFUSA,interventional,"the percentage of malignant prostate tumors detected very early is constantly increasing and the number of well differentiated tumors, with small volume and low risk of progression increases. when a tumor of this type is identified, radical prostatectomy remains the reference treatment, but this treatment is not without side effects. active surveillance is a strategy which aims at detecting an early development of the cancerous disease in order to propose curative treatment in a timely manner and thus improve specific survival. patients are therefore re-evaluated each year by rectal examination, psa (prostate-specific antigen) assay. active surveillance remains difficult to manage psychologically for both the patient and the practitioner, because of the lack of treatment on the one hand and a rate of non-curable cancers close to 50% when signs of progression trigger a radical treatment.

the aim of the focal treatment hifu (high intensity focused ultrasound) is to destroy the cancer without causing side effects in contrast to radical treatments. it is in this sense that it is positioned both as an alternative to radical surgery and as an alternative to active surveillance.","inclusion criteria:

patient having been clearly informed of the study and having accepted, with sufficient reflection time, to participate by signing the informed consent form of the study.
age between 50 and 80 years with a life expectancy of more than 5 years. patients between the ages of 75 and 80 will need to have g8 score > 14.

initial diagnosis of localized prostate cancer (t1c or t2a) with the following characteristics:

only one target tumor on mri on a maximum of 2 contigous sextants. case allowed:

if more than one target tumor on mri, only one of them must be confirmed by targeted prostate biopsies.
if no target tumor on mri, only 2 contigous sextants must be positive on prostate biopsies
a maximum tumor length> 3 mm or at least 3 positive biopsies on all biopsies performed (randomized biopsies and/or mri/ultrasound fusion-guided prostate biopsy).
gleason 6 score (risk group 1 of the d'amico classification).
tumor positioned so that a safety distance of at least 9 mm from external sphincter can be defined during hifu-focal treatment in prostate tissue around the target.
psa ≤ 15ng / ml.
patient affiliated with health insurance or beneficiary of an equivalent plan.

exclusion criteria:

contraindications to treatment with hifu-f:

tumor not accessible.
multiple intra prostatic calcifications inducing, on ultrasound, a shadow cone in the prostate preventing the penetration of ultrasound and thus the realization of the treatment.
history of pelvic irradiation
presence of an implant (stent, catheter) located less than 1 cm from the treatment area.
fistula of the urinary tract or rectum.
anal or rectal fibrosis, anal or rectal stenosis or other abnormalities making it difficult to insert the focal one® probe.
anatomical abnormality of the rectum or rectal mucosa.
patient with artificial sphincter, penile prosthesis or intra prostatic implant, eg stent.
history of intestinal inflammatory pathology.
uro-genital infection in progress (the infection to be treated before hifu treatment).
anterior surgery at the level of the anus or rectum making the introduction of the probe impossible.
allergy to latex.
thickness of the rectal wall> 10mm.
turp indication. bladder neck incision is allowed .
patient with a medical contraindication to sonovue® injection.
patient with a medical contraindication on mri.
patient already treated for prostate cancer (hormone therapy, radiotherapy, surgery).
history of uncontrolled cancer and / or treated for less than 5 years (with the exception of basal cell skin cancer).
history of sclerosis of the bladder neck or urethral stenosis.
patient with a several bleeding risk according to medical advice (patient with oral anticoagulant therapy must receive an alternative therapy if randomized in hifu-f arm).
patients with unstable neurological pathology.
patient who has been treated for a therapeutic trial within 30 days of enrollment or who wishes to participate in an ongoing study that may interfere with this study.
legal person protected by law.
patient not able to understand the objectives of the study or refusing to comply with postoperative instructions.",1,0,0,1,0,0,50.0,80.0,Prostate,Prostate,0,0,Male
173,173,173,932,NCT03534713,2023-09-18,induction chemotherapy followed by standard therapy in cervical cancer with aortic lymph node spread,"phase iii study comparing neoadjuvant chemotherapy with carboplatin and paclitaxel followed by standard therapy, with standard therapy alone in women with cervical cancer and para aortic positive lymph node.",ONCOCOL01,interventional,"the main objective of this study is to determine whether neoadjuvant chemotherapy with carboplatin and paclitaxel plus standard cisplatin-based chemoradiation with extended fields improves overall survival rates compared to standard therapy alone in women with cervical cancer with paraaortic lymph node involvement.

women in the experimental arm will receive neoadjuvant chemotherapy with carboplatin and paclitaxel every 21 days during 3 cycles followed by standard therapy with extended field external radiation therapy and concomitant chemotherapy. women in the control arm will receive standard therapy with extended field external radiation therapy and concomitant chemotherapy.

310 patients will be recruited during 4.5 years, with 3 years of follow up period.","inclusion criteria:

women with histologically proven invasive carcinoma of the uterine cervix and para aortic lymphadenopathy determined by either a positive positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro- d-glucose integrated with computed tomography or if negative positron emission tomography computed tomography based on histological examination of paraaortic lymph node dissection.
performance status eastern cooperative oncology group 0-2
stage international federation of gynecology and obstetrics ib1 to iva at diagnosis with para-aortic lymph node involvement
adenocarcinoma or squamous cell carcinoma or adenosquamous carcinoma
adequate renal function (creatinine clearance ≥60 ml/min)
adequate hepatic function (bilirubin <1.5 times normal and serum glutamooxaloacetate transferase < 3 times normal)
adequate hematopoietic function platelet count > 100x10 9/l and absolute neutrophil count > 1.5x10 9/l)
written informed consent for participation

exclusion criteria:

stage federation of gynecology and obstetrics ivb at diagnosis
others histologies than adenocarcinoma, squamous cell carcinoma and adenosquamous carcinoma.
women who receive any prior chemotherapy for her cervical cancer
pregnant or lactating women
prior ( within the last 5 years) malignancies other than non-melanoma skin cancer
inadequate renal, hepatic or hematopoietic function (cf previously)
cardiovascular pathology new york heart association ii or more
pre-existing peripheral neuropathy common toxicity criteria grade ≥ 2",1,0,0,1,0,0,18.0,200.0,Pleura,Pleura,0,1,Female
174,174,174,935,NCT03539744,2023-10-30,a study designed to evaluate the safety and efficacy of venetoclax plus dexamethasone (vendex) compared with pomalidomide plus dexamethasone (pomdex) in participants with t(11;14)-positive relapsed or refractory multiple myeloma.,"a phase 3, multicenter, randomized, open label study of venetoclax and dexamethasone compared with pomalidomide and dexamethasone in subjects with t(11;14)-positive relapsed or refractory multiple myeloma",,interventional,a study designed tocompare progression-free survival (pfs) in participants with t(11;14)-positive mm treated with venetoclax in combination with dexamethasone versus pomalidomide in combination with dexamethasone.,"inclusion criteria:

documented diagnosis of multiple myeloma (mm) based on standard international myeloma working group (imwg) criteria.
measurable disease at screening as defined per protocol.
has received at least 2 prior lines of therapy as described in the protocol.
has had documented disease progression on or within 60 days after completion of the last therapy.
has received at least 2 consecutive cycles of lenalidomide and be relapsed/refractory to lenalidomide, as defined per protocol.
has received at least 2 consecutive cycles of a proteasome inhibitor (pi).
has t(11;14)-positive status determined by an analytically validated fluorescent in situ hybridization (fish) assay per centralized laboratory testing.
an eastern cooperative oncology group (ecog) performance status less than or equal to 2.
laboratory values (liver, kidney and hematology laboratory values) that meet criteria as described per protocol.

exclusion criteria:

history of treatment with venetoclax or another b-cell lymphoma (bcl)-2 inhibitor or pomalidomide.
history of other active malignancies, including myelodysplastic syndromes (mds), within the past 3 years (exceptions described in the protocol).
evidence of ongoing graft-versus-host disease (gvhd) if prior stem cell transplant (sct).
prior treatment with any of the following: allogeneic or syngeneic sct within 16 weeks prior to randomization; or autologous sct within 12 weeks prior to randomization.
known central nervous system involvement of mm.
concurrent conditions as listed in the protocol.",1,0,0,1,0,0,18.0,200.0,Vulva,Pleura,0,0,All
175,175,175,937,NCT03541330,2023-01-26,information and accompaniment of siblings following the announcement of a cancer in pediatric hematology.,information and accompaniment of siblings following the announcement of a cancer in pediatric hematology.,,interventional,the primary objective is to evaluate the experience with the information received on the disease by the healthy brothers and sisters of childrens with malignant haemopathy at the centre hospitalier régional et universitaire of lille,"inclusion criteria:

children from 6 to 12 years old
brother or sister of a child:

o has malignant haemopathy o follow-up in the pediatric hematology department in lille, o diagnosed from 6 weeks to 1 year before maintenance of the healthy subject included

whose parents are able to understand and sign voluntarily informed consent
affiliated to a social security scheme
ability to understand and answer questions alone during the semi-structured interview

exclusion criteria:

child under 6 years or over 12 years
subject with a pathology that may interfere with the course of the study, according to the investigator's assessment
absence of the informed consent of one of the parents and / or the legal representative
refusal of participation of the subject",1,0,0,0,0,1,6.0,12.0,Pleura,Pleura,0,0,All
176,176,176,939,NCT03545256,2023-02-22,sentinel. ambulatory. oral cavity. oropharynx (s.a.c.o),open non-randomized study on the management of operable t1-n0 or t2-n0 oral cavity and oropharynx cancer and sentinel lymph node in outpatient surgery,SACO,interventional,"this is a single-center pilot study of open-label, non-randomized interventional research based on the outpatient management of 30 patients with t1-n0 or t2-n0 cancer in the oral cavity or oropharynx.","inclusion criteria:

male or female over 18 years old with no upper age limit
patient (s) affiliated to a social security system, or beneficiary of such a system
patient information and informed consent signed by the patient
patient no longer participating in another trial since legal time
patient with primary squamous cell carcinoma of the oral cavity or oropharynx documented by biopsy with histological analysis less than 1 month old
tumor operable by tnm stage, location and general condition of the patient
systematic oto-rhino-laryngology panendoscopy eliminating a second synchronous tumor and establishing precisely the t
stage t1 or t2, n0 and m0
proposal by a multidisciplinary meeting for tumor surgery and gs technique
eligibility criteria for ambulatory surgery present
anesthetic criteria for eligibility for outpatient hospitalization (ref afar 29 (2010) 67-72, formalized expert recommendations) including asa i, ii and iii score stable
patient able to understand the nature, purpose and methodology of the study

exclusion criteria:

lack of one of the inclusion criteria
other cancer being treated
non-infiltrating tumor: high grade dysplasia, carcinoma in situ
insufficient tumor excision: invaded margins without complementary recovery in healthy zone
contraindication to sentinel lymph node surgery or ganglion dissection
contraindication to radiotherapy
contraindications to performing a scintigraphy:
known allergy or intolerance to the injected product and in particular to technetium-99
pregnancy
refusal to accept the entire treatment (nodal diagnosis on gs, lymph node dissection pn + follow-up of adjuvant radiotherapy if necessary)
impossible to follow over 2 years
refusal to accept the monitoring described and / or to provide the information necessary for the study
patient already treated for this tumor outside of an excisional biopsy
patient who previously had chemotherapy or immunotherapy for another cancer outside the vads in a period of less than 6 months
patient who has had cervical or vads radiotherapy regardless of the cause or delay
patient who has had previous cervical surgery regardless of cause or delay
patient protected by law (patient under guardianship).
patient (e) deprived of liberty by administrative decision.
pregnant or lactating women according to article l1121-5 of the csp. an assay of βhcg will be performed routinely to ensure the absence of pregnancy.",1,0,0,0,0,1,18.0,200.0,Other,Other,0,1,All
177,177,177,940,NCT03547973,2023-10-18,study of sacituzumab govitecan in participants with urothelial cancer that cannot be removed or has spread,a phase ii open-label study of sacituzumab govitecan in unresectable locally advanced/metastatic urothelial cancer,TROPHY U-01,interventional,the objective of this study is to evaluate the efficacy and safety of sacituzumab govitecan-hziy monotherapy and with novel combinations in participants with metastatic urothelial cancer (muc).,"key inclusion criteria:

female or male individuals, ≥ 18 years of age (19 years old for south korea).
individuals with histologically confirmed urothelial cancer (uc).
eastern cooperative oncology group (ecog) performance status score of 0 or 1.

cohort 1: have had progression or recurrence of urothelial cancer following receipt of platinum-containing regimen (cisplatin or carboplatin):

received a first-line platinum-containing regimen in the metastatic setting or for inoperable locally advanced disease;
or received neo/adjuvant platinum-containing therapy for localized muscle-invasive urothelial cancer, with recurrence/progression ≤12 months following completion of therapy.
cohort 1: in addition to above criterion, have had progression or recurrence of urothelial cancer following receipt of an anti-programmed cell death protein 1 (anti-pd-1)/ anti-programmed death ligand 1 (pd-l1) therapy.
cohort 2: were ineligible for platinum-based therapy for first line metastatic disease and have had progression or recurrence of urothelial cancer after a first-line therapy for metastatic disease with anti-pd-1/pd-l1 therapy. individual may not have received any platinum for treatment of recurrent, metastatic or advanced disease.
cohort 3: progression or recurrence of uc following a platinum containing regimen in the metastatic setting, or progression or recurrence of uc within 12 months of completion of platinum-based therapy as neoadjuvant or adjuvant therapy.
cohort 4: individual has not received any platinum-based chemotherapy in the metastatic or unresectable locally advanced setting. creatinine clearance of at least 50 ml/min calculated by cockcroft-gault formula or another validated tool. for individuals receiving cisplatin at 70 mg/m^2 on day 1 of every 21-day cycle, a creatinine clearance of least 60 ml/min calculated by cockcroft -gault formula or another validated tool is required. individuals with creatinine clearance between 50 to 59 ml/min are to receive a split dose of cisplatin (35 mg/m^2 day 1 and day 8 of every 21-day cycle).
cohorts 4, 5, 6: archival tumor tissue comprising muscle-invasive or metastatic urothelial carcinoma, or a biopsy of metastatic urothelial carcinoma.

cohort 5: individuals received at least 4 cycles and no more than 6 cycles of gem + cisplatin. no other chemotherapy regimens are allowed in this cohort, with the exception of prior adjuvant or neoadjuvant systemic therapy with curative intent after > 12 months from completion of therapy.

no evidence of progressive disease following completion of first-line chemotherapy (ie, cr, pr, or sd per recist v1.1 guidelines as per investigator).
treatment-free interval of 4 to 10 weeks since the last dose of chemotherapy.
cohort 6: cis-ineligible and no prior therapy for metastatic disease or for unresectable locally advanced disease. checkpoint inhibitor therapy naïve or >12 months from completion of adjuvant therapy are permitted.
cohorts 4 and 6: have measurable disease by ct or mri as per recist 1.1 criteria. tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
cohorts 1, 2, 3 and 5: creatinine clearance ≥ 30 ml/min as calculated by the cockcroft-gault formula unless otherwise specified
adequate renal and hepatic function.
adequate hematologic parameters without transfusional support.
individuals must have a 3-month life expectancy.

key exclusion criteria:

females who are pregnant or lactating.
has had a prior anti-cancer monoclonal antibody (mab) within 4 weeks prior to study day 1 or who has not recovered (i.e., ≤ grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (ie, ≤grade 1 from aes due to a previously administered agent).
for cohort 5: alopecia, sensory neuropathy grade ≤2 is acceptable, or other grade < 2 adverse events not constituting a safety risk based on the investigator's judgment are acceptable.
requires concomitant medication interfering with ugt1a1 with no alternate option available.
has an active second malignancy.
has known active central nervous system (cns) metastases and/or carcinomatous meningitis.
has known active hepatitis b or hepatitis c.
has other concurrent medical or psychiatric conditions.
cohort 3: has received anti-pd-1/pd-l1 therapy previously.
cohorts 3 to 5: has an active autoimmune disease that required systemic treatment in past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
cohorts 3 to 6: has received a live vaccine within 30 days prior to the first dose of study drug(s), has history or evidence of interstitial lung disease (ild) or non-infectious pneumonitis.
cohort 4: refractory to platinum (i.e., relapsed ≤ 12 months after completion of chemotherapy) in the neoadjuvant/adjuvant setting.
cohorts 4, 5, and 6: for individuals who received prior cpi, a treatment-free interval >12 months between the last treatment administration and the date of recurrence is required.

note: other protocol defined inclusion/exclusion criteria may apply.",1,0,1,0,0,0,18.0,200.0,Bladder,Bladder,0,0,All
178,178,178,941,NCT03548428,2022-07-22,stereotaxic body irradiation of oligometastase in sarcoma (stereosarc),"randomized phase ii, 2-arm study of immunomodulation with atezolizumab concomitant with high dose radiation (sbrt) versus sbrt alone in patients with oligometastatic sarcomas",Stereosarc,interventional,"up to 50% of soft tissue sarcoma (sts) patients will develop metastases in the course of their disease. cytotoxic therapy is a standard treatment in this setting but yields average tumor response rates of 25% at first line and ≤10% at later lines. it is also limited in the number of lines and courses by tolerance issues. trials include poly/oligometastases indistinctively and suggest that consolidation ablation is used in ~20% of patients with residual oligometastases refractory to chemotherapy. oligometastases represent a stage of disease between completely absent and widely metastatic, and which might be cured if the limited numbers of metastatic sites are eradicated. ablative strategies to treat patients with oligometastases from sarcomas yield prolonged survival times and stereotactic body radiation therapy (sbrt) is associated with excellent tolerance. surgery may be offered in selected metastatic cases. alternatively and increasingly, sbrt yields high control rates at treated sites (≥ 80%). the so-called radioresistance of sarcomas is overcome by the high doses per fraction made possible owing to the high precision achieved with sbrt. sbrt is an accepted treatment strategy provided that tumor burden remains limited in the number and size of metastases. systemic treatment can be combined with sbrt. sbrt may produce abscopal effects where tumors outside the irradiation area also demonstrate tumor shrinkage in some occurrences. sbrt produces systemic antitumoral immune response in certain conditions and enhances radiation-induced tumor cell death compared to conventional lower dose irradiation. abscopal effects have been potentialized with sbrt/immunotherapy in several tumor models. sarcomas are a privileged target tumor given their high metastatic propensity.

several potent immunomodulators that skew the tumor immune microenvironment toward a proimmunity context are being investigated in sts either alone or in combination with chemotherapy or targeted therapy. the pd-1 receptor is present within the tumor microenvironment, and limits the activity of infiltrating cytotoxic t lymphocytes, thus blocking effective immune responses. the action of pd-1 is triggered upon binding to its ligands. pd-1 can stimulate the immunosuppressive function of regulatory t cells. moreover, blockade of pd-1 can stimulate anti-tumor immune responses. significant responses have been obtained in several sarcomas with acceptable tolerance. preliminary clinical experience suggests that immunotherapy can be efficient in refractory leiomyosarcomas. several drugs targeting the pd-1/pd-l1/2 axis are ongoing either as single agents or in combination with ipilimumab, kinase inhibitors, or chemotherapy in sts subtypes. combination of radiotherapy with immunotherapy is included as a means of increasing tumor antigen release in metastatic sts. immunomodulated sbrt is a particularly attractive strategy, given the potential of radiation to induce cytotoxicity in tumors and induce abscopal effects. a phase ii radiation trial showed increased apoptosis-, intra-tumoral dendritic cells and accumulation of intratumoral t cells in sts with correlation with tumor-specific immune responses.

we here propose a randomized phase ii study to prolong progression-free survival (pfs) with the combination of sbrt/immunotherapy in oligometastatic sts patients.

sbrt is well-tolerated with hardly any severe toxicity (fewer than 5% acute and late grade 3 toxicities). it is performed in an ambulatory setting in only a few treatment fractions. associations between irradiation and immunomodulatory agents appear to be synergistic and show favorable tolerance profiles. immunomodulatory agents have a more favorable toxicity profile than cytotoxic agents with about 65% overall acute toxicities. immunotherapy selectively binds to pd-l1 and competitively blocks its interaction with pd-1.

compared with anti-pd-1 antibodies that target t-cells, immunotherapy targets tumor cells, and is therefore may induce fewer side effects, including a lower risk of autoimmune-related safety issues, as blockade of pd-l1 leaves the pd-l2 - pd-1 pathway intact to promote peripheral self-tolerance.

stereotactic irradiation is associated with an excellent tolerance with rates of grade 3 or more toxicities below 5%.

preliminary data of toxicity with the association of stereotactic irradiation and immunotherapy show no cumulative toxicity in association with immunotherapy. however, their incidence and characteristics are no different from that observed with stereotactic irradiation alone. moreover, intracranial metastases are exceptional in sarcomas.

the toxicity of the association for extracranial stereotactic irradiation does not seem to be increased either.","inclusion criteria:

• sts (leiomyosarcomas uterine/extra-uterine, liposarcomas, undifferentiated sarcomas), any grade

progressive disease according to recist 1.1 criteria,
metastatic disease (1-5 synchronous macroscopic metastases by chest and abdominopelvic ct, maximal cumulated diameter 10 cm); any anatomic site
first or second metastatic line
be ≥ 18 years of age on day of signing informed consent.
have a performance status of 0 or 1 on the ecog performance scale.
have at least one lesion mesurable by recist 1.1 for irradiation with a size of < 5 cm.
demonstrate adequate organ function: absolute neutrophil count (anc) ≥1,500 /mcl; platelets ≥100,000 / mcl; hemoglobin ≥9 g/dl or ≥5.6 mmol/l; serum creatinine ≤1.5 x upper limit of normal (uln) or measured or calculated creatinine clearance (gfr can also be used in place of creatinine or crcl) ≥50 ml/min for subject with creatinine levels > 1.5 x institutional uln; serum total bilirubin ≤ 1.5 x uln or direct bilirubin ≤ uln for subjects with total bilirubin levels > 1.5 uln; ast (sgot) and alt (sgpt) ≤ 2.5 x uln or ≤ 5 x uln for subjects with liver metastases. all screening labs should be performed within 15 days of treatment initiation.
female subjects of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
surgical ablation (or other ablative methods such as thermal ablative methods) remains possible if needed before sbrt, at least 4 weeks before randomisation and provided that at least one lesion needs to be treated by sbrt.
ffpe tumor tissue collected before sbrt is available for immunohistochemistry (optional)
archival metastatic biopsy blocks (or slides) on paraffin embedded samples available. if no archival material is available, a fresh biopsy should be performed if possible.
be willing and able to provide written informed consent/assent for the trial.
affiliated with a health insurance system.

exclusion criteria:

is currently participating in, or has participated in, a study of an investigational agent or using an investigational device within 4 weeks prior to randomisation.
has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
has had a prior monoclonal antibody within 4 weeks prior to randomisation or has not recovered (i.e., ≤ grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
has had prior chemotherapy or targeted small molecule therapy within 4 weeks prior to randomisation or who has not recovered (i.e. ≤ grade 1 or at baseline) from adverse events due to a previously administered agent (subjects with ≤ grade 2 neuropathy are an exception to this criterion and may qualify for the study). if subjects received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
have had previous radical radiation to any tumour site within 4 weeks prior to randomisation
have had previous ablative treatment within 4 weeks prior to randomisation (radiofrequency, surgery)
has a tumour within 5 mm of the spinal cord (owing to rare reported cases of flare-up after initiation of immunotherapy)
has a known additional malignancy that is progressing or requires active treatment. exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. subjects with hypothyroidism stable on hormone replacement or sjögren's syndrome will not be excluded from the study.
has evidence of symptomatic interstitial lung disease or an active, non-infectious pneumonitis.
has an active infection requiring systemic therapy.
has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
has known psychiatric or substance-abuse disorders that would interfere with cooperation with the requirements of the trial.
is pregnant or breastfeeding, or expecting to conceive within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
has received prior therapy with an anti-pd-1, anti-pd-l1, anti-pd-l2, anti-cd137, or anti-cytotoxic t-lymphocyte-associated antigen-4 (ctla-4) antibody (including ipilimumab or any other antibody or drug specifically targeting t-cell co-stimulation or checkpoint pathways).
has a known history of human immunodeficiency virus (hiv) (hiv 1/2 antibodies).
has known active hepatitis b (e.g. hbsag reactive) or hepatitis c (e.g. hcv rna [qualitative] is detected).
has received a live vaccine within 30 days prior to the first dose of trial treatment.
has had major surgery or major blood transfusions (>3 packed cells) in the past 3 months.
receives il-2, interferon or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigational therapies; or chronic use of systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses)
under-age patients
patients unable to express their consent
vulnerable persons as defined by article l1121-5 - 8:
pregnant women, women in labor or breast-feeding mothers, persons deprived of their freedom by judicial or administrative decision, persons hospitalized without their consent by virtue of articles l. 3212-1 and l. 3213-1 and who are not subject to the provisions of article l. 1121-8
persons admitted to a social or health facility for reasons other than research
adults subject to a legal protection order or unable to give their consent",1,0,1,0,0,0,18.0,200.0,Pleura,Brain,0,0,All
179,179,179,942,NCT03549715,2022-04-21,neoadjuvant dose-dense mvac in combination with durvalumab and tremelimumab in muscle-invasive urothelial carcinoma,neoadjuvant dose-dense mvac in combination with durvalumab (medi4736) and tremelimumab in muscle-invasive urothelial carcinoma,NEMIO,interventional,"this is an open label, phase i/ii clinical trial to evaluate the efficacy and safety of 2 cycles of durvalumab without (arm a) or with (arm b) tremelimumab in association with ddmvac as neoadjuvant therapy in patients with miuc.","inclusion criteria:

written informed consent and any locally required authorization (e.g., eu data privacy directive in the eu) obtained from the patient prior to performing any protocol-related procedures, including screening evaluations
age ≥18 years at time of study entry
histologically confirmed miuc (also termed tcc) of the bladder. patients with mixed histologies are required to have a dominant transitional cell pattern (urothelial carcinoma must be > 50%)
localized miuc of the bladder with clinical stage t2-t4a and ≤n1 disease ( the single lymph node must be < 15 mm (short axis) on imaging
patients with urothelial carcinoma of the prostatic urethra
bodyweight >45kg

patients eligible for cisplatin-based neoadjuvant chemotherapy, including:

creatinine clearance (cl) >60 ml/min based on the modification of diet in renal disease study (mdrd) formula
cardiac left ventricular ejection fraction (lvef) ≥50%
eastern cooperative oncology group (ecog) performance status of 0 or 1
absence of metastasis, as confirmed by a negative baseline ct or mri scan of the pelvis, abdomen, and chest no more than 4 weeks prior to randomization. patients with clinical stage n1 disease are eligible if the single lymph node measures ≤2 cm in greatest dimension.

adequate organ and marrow function as defined below (obtained within 14 days prior to the first study treatment):

hemoglobin ≥10.0 g/dl (patients may be transfused to meet this criterion)
absolute neutrophil count (anc) ≥1500 cells/μl (without g-csf support within 2 weeks prior to cycle 1, day 1)
wbc counts >2500/µl
platelet count ≥100,000/µl (without transfusion within 2 weeks prior to cycle 1, day 1)
serum bilirubin ≤1.0 x institutional upper limit of normal (uln). patients with known gilbert disease who have serum bilirubin level ≤3 x uln may be enrolled.
ast, alt, and alkaline dehydrogenase ≤2.5 x uln
partial thromboplastin time/prothrombin time (ptt/pt) ≤1.5 x uln or international normalized ratio (inr) <1.7 x uln

evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. the following age-specific requirements apply:

women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)
women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
women of childbearing potential and non-sterilized males who are sexually active with a female partner of childbearing potential must be willing to use contraceptive methods during the treatment period and for at least 6 months after the last dose of treatment
patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

exclusion criteria:

urothelial carcinoma of the upper tract
any approved anti-cancer therapy for urothelial carcinoma, including chemotherapy, or immunotherapy prior to initiation of study treatment. of note, previous intravesical bcg injections are allowed if administered for non-muscle invasive urothelial carcinoma
primary chemoradiation for bladder preservation for urothelial carcinoma of the bladder
impaired renal function (glomerular filtration rate [gfr]<60 ml/min); gfr should be assessed by calculation from serum/plasma creatinine (mdrd formula)
uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring aes or compromise the ability of the patient to give written informed consent

grade 2 or greater hearing loss that contraindicates cisplatin use. threshold shift of >25 decibel averaged at 2 contiguous test frequencies in least one ear.

exception: patients with grade 2 hearing loss diagnosed on the audiogram that are asymptomatic (no complain of hearing loss and no tinnitus) can be enrolled in the study.

grade 2 or greater peripheral neuropathy
oral anticoagulation treatment (vitamin k antagonist should be replaced by low-molecular-weight heparin).
treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days or five half-lives of the drug
concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
any concurrent chemotherapy, investigational product, biologic, or hormonal therapy for cancer treatment. concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable
major surgical procedure (as defined by the investigator) other than for diagnosis within 28 days prior to cycle 1
history of prior organ transplantation, including stem cell allografting
history of autoimmune disease, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, wegener's granulomatosis, sjögren's syndrome, guillain-barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone and type i diabetes mellitus on stable dose of insulin may be eligible for this study
all micropapillary and plasmacytic forms, with or without squamous cell adenocarcinoma
severe infections within 4 weeks prior to cycle 1, day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
signs or symptoms of infection within 2 weeks prior to cycle 1, day 1
receipt of therapeutic oral or iv antibiotics within 2 weeks prior to cycle 1, day 1
significant cardiovascular disease, such as new york heart association cardiac disease (class ii or greater), myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina

history of another primary malignancy within 3 years prior to cycle 1, day 1, except for:

localized low-risk prostate cancer (defined as stage ≤t2b, gleason score ≤7, and prostate-specific antigen [psa] at prostate cancer diagnosis ≤20 ng/ml [if measured]) treated with curative intent and without psa recurrence low-risk prostate cancer (defined as stage t1/t2a, gleason score <7, and psa ≤10 ng/ml) who are treatment-naive and undergoing active surveillance patients with malignancies of a risk of metastasis/death (e.g., risk of metastasis or death <5% at 5 years) are eligible after investigator's approval if they meet both of the following criteria: malignancy treated with expected curative intent, and no evidence of recurrence or metastasis by follow-up imaging and any disease-specific tumor markers

history of leptomeningeal carcinomatosis
history of idiopathic pulmonary fibrosis, organizing pneumonia
serum albumin <25 g/l
lvef <50%
mean qt interval corrected for heart rate using fridericia's formula (qtcf) ≥470 ms calculated from 3 electrocardiograms (ecgs) within 15 minutes at 5 minutes apart
active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tb testing in line with local practice), hepatitis b (known positive hbv surface antigen (hbsag) result), hepatitis c, or human immunodeficiency virus (positive hiv 1/2 antibodies). patients with a past or resolved hbv infection (defined as the presence of hepatitis b core antibody [anti-hbc] and absence of hbsag) are eligible. patients positive for hepatitis c (hcv) antibody are eligible only if pcr is negative for hcv rna

current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. the following are exceptions to this criterion:

intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent steroids as premedication for hypersensitivity reactions (e.g., ct scan premedication)

receipt of live attenuated vaccine within 30 days prior to the first dose of study treatment. note: patients, if enrolled, should not receive live vaccine whilst receiving study treatment and for up to 30 days after the last dose of study treatment
female patients who are pregnant or breastfeeding, or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy or 180 days after the last dose of durvalumab + tremelimumab combination therapy
known allergy or hypersensitivity to chimeric or humanized antibodies or fusion proteins, or to any of the study drugs or study drug excipients
prior randomisation or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment
any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that, in the opinion of the investigator, makes the patient unsuitable for participation in the study procedures for withdrawal of incorrectly enrolled patients are presented in section 4.3 if a patient withdraws from participation in the study, then his or her enrollment/randomization code cannot be reused. withdrawn patients will not be replaced.",1,1,1,0,0,0,18.0,200.0,Vulva,Brain,0,0,All
180,180,180,947,NCT03564340,2023-11-01,study of regn4018 administered alone or in combination with cemiplimab in adult patients with recurrent ovarian cancer,a phase 1/2 study of regn4018 (a muc16xcd3 bispecific antibody) administered alone or in combination with cemiplimab in patients with recurrent ovarian cancer,,interventional,"primary objectives

in the dose escalation phase:

• to assess the safety and pharmacokinetics (pk) in order to determine a maximally tolerated dose (mtd) or recommended phase 2 dose (rp2d) of regn4018 as monotherapy and in combination with cemiplimab.

in the dose expansion phase:

• to assess the preliminary efficacy of regn4018 as monotherapy and in combination with cemiplimab, (separately by cohort) as determined by the objective response rate (orr) by response evaluation criteria in solid tumors (recist) 1.1

secondary objectives

in the dose escalation phase:

• to assess the preliminary efficacy of regn4018 as monotherapy and in combination with cemiplimab (separately by cohort) as determined by orr by recist 1.1

in the dose expansion phase:

to characterize the safety profile in each expansion cohort
to characterize the pk of regn4018 as monotherapy and in combination with cemiplimab.
to assess the effects of regn4018 as monotherapy and in combination with cemiplimab on patient-reported outcomes (pros), including health-related quality of life (hrqol), functioning, and symptoms

in both the dose escalation and dose expansion phases:

to assess preliminary efficacy of regn4018 as monotherapy and in combination with cemiplimab (separately by cohort) as measured by orr based on irecist, best overall response (bor), duration of response (dor), disease control rate, complete response (cr) rate and progression-free survival (pfs) based on recist 1.1 and irecist
to assess efficacy of regn4018 as monotherapy and in combination with cemiplimab as measured by ca-125 level.
immunogenicity of regn4018 and cemiplimab","key inclusion criteria:

patients with histologically or cytologically confirmed diagnosis of advanced, epithelial ovarian cancer (except carcinosarcoma), primary peritoneal, or fallopian tube cancer who have all of the following:

serum ca-125 level ≥2x upper limit of normal (uln) (in screening)
has received at least 1 line of platinum-containing therapy or must be platinum-intolerant (applicable for dose escalation and non-randomized dose expansion cohorts)
documented relapse or progression on or after the most recent line of therapy
no standard therapy options
adequate organ and bone marrow function as defined in the protocol
life expectancy of at least 3 months
randomized phase 2 expansion cohorts only: platinum resistant ovarian cancer patients who have had 1 to 4 lines of platinum-based therapy and prior treatment with a poly adp-ribose polymerase (parp) inhibitor or bevacizumab as defined in the protocol.

key exclusion criteria:

recent treatment with anti-programmed cell death (pd-1)/pd-l1 therapy
expansion cohort only: more than 4 prior lines of cytotoxic chemotherapy
prior treatment with a mucin 16 (muc16)-targeted therapy
untreated or active primary brain tumor, central nervous system (cns) metastases, or spinal cord compression
history and/or current cardiac findings as defined in the protocol
severe and/or uncontrolled hypertension at screening. patients taking anti-hypertensive medication must be on a stable anti-hypertensive regimen

note: other protocol inclusion/exclusion criteria apply",1,1,1,0,0,0,18.0,200.0,Pleura,Pleura,0,0,Female
181,181,181,950,NCT03568188,2022-03-15,efficacy evaluation of focused hifu (high intensity focused ultrasound) therapy in patients with localized intermediate risk prostate cancer,"phase 2, multicenter, prospective cohort study, estimating the efficacy of focused hifu therapy in patients with localized intermediate risk prostate cancer",FOCALE,interventional,"the aim of the focal treatment hifu is to destroy the cancer without causing side effects in contrast to radical treatments. radical treatments (surgery or radiation therapy) are the standard therapies for patient with intermediate risk localized prostate cancer and good life expectancy (prostatectomy if life expectancy10 years) by destroying only the part of the gland that harbors cancer, it may indeed be possible to provide efficient cure of the disease while minimizing treatment-induced morbidity (incontinence and loss of potency). around 20% of patients presented with a unilateral tumor: this patients are currently treated radically. no study published papers reported outcomes of a large population (>100) with intermediate risk cancers treated with focal-hifu (conducted with the focal one® device). focal therapy must be only offer within clinical trial setting (eau (european association of urology) guidelines ). the aim of this cohort will be to determine the success rate of focal-hifu in this intermediate risk population. the result the study will be used for calculation the arms of a future random study","inclusion criteria:

patient having been clearly informed of the study and having accepted, with sufficient reflection time, to participate by signing the informed consent form of the study.
age between 50 and 80 years with a life expectancy of more than 5 years. patients between the ages of 75 and 80 will need to have a g8 score > 14.

initial diagnosis of localized prostate cancer (t1c or t2a) with the following characteristics:

a multiparametric mri showing a single invasive tumor focus at most two contiguous sextants confirmed by biopsies (index tumor). patients with multiple suspected mri foci may be included if only one of these foci is confirmed by targeted biopsies.
gleason score= 7 (3+4).
tumor accessible to a focal-hifu treatment. for apical tumor, it must be localized more than 9 mm from the external sphincter
psa ≤ 15ng / ml.
patient affiliated with health insurance or beneficiary of an equivalent plan.

exclusion criteria:

contraindications to treatment with hifu-f:

tumor not accessible.
multiple intra prostatic calcifications inducing, on ultrasound, a shadow cone in the prostate preventing the penetration of ultrasound and thus the realization of the treatment.
history of pelvic irradiation
presence of an implant (stent, catheter) located less than 1 cm from the treatment area.
fistula of the urinary tract or rectum.
anal or rectal fibrosis, anal or rectal stenosis or other abnormalities making it difficult to insert the focal one® probe.
anatomical abnormality of the rectum or rectal mucosa.
patient with artificial sphincter, penile prosthesis or intra prostatic implant, eg stent.
history of intestinal inflammatory pathology.
uro-genital infection in progress (the infection to be treated before hifu treatment).
anterior surgery at the level of the anus or rectum making the introduction of the probe impossible.
allergy to latex.
thickness of the rectal wall> 10mm.
turp indication. bladder neck incision is allowed.
patient with a medical contraindication to sonovue® injection.
patient with a medical contraindication on mri.
patient already treated for prostate cancer (hormone therapy, radiotherapy, surgery).
history of uncontrolled cancer and / or treated for less than 5 years (with the exception of basal cell skin cancer).
history of pelvic radiotherapy.
history of sclerosis of the bladder neck or urethral stenosis.
patient with a several bleeding risk according to medical advice (patient with oral anticoagulant therapy must receive an alternative therapy).
patients with unstable neurological pathology.
patient who has been treated for a therapeutic trial within 30 days of enrollment or who wishes to participate in an ongoing study that may interfere with this study.
legal person protected by law.
patient not able to understand the objectives of the study or refusing to comply with postoperative instructions.",1,0,1,0,0,0,50.0,80.0,Prostate,Prostate,0,0,Male
182,182,182,952,NCT03568656,2023-09-14,study to evaluate ccs1477 in advanced tumours,"an open-label phase i/iia study to evaluate the safety and efficacy of ccs1477 as monotherapy and in combination, in patients with advanced solid/metastatic tumours.",,interventional,"a phase 1/2a study to assess the safety, tolerability, pk and biological activity of ccs1477 in patients with metastatic castration resistant prostate cancer, metastatic breast cancer, non-small cell lung cancer or advanced solid tumours.","inclusion criteria:

provision of consent
ecog performance status 0-1
assessable disease (by ct, mri, bone scan or x-ray)
adequate organ function
highly effective contraception measures for duration of study

additional inclusion criteria for mcrpc patients only:

previously received abiraterone and/or enzalutamide (or equivalent anti-androgen), and docetaxel (unless ineligible or refused)

progressive disease documented by one or more of the following:

biochemical progression defined as at least 2 stepwise increases in a series of any 3 psa values
progression as defined by recist v1.1 guideline for assessment of malignant soft tissue disease.
progression defined as two or more new metastatic bone lesions confirmed on bone scan from a previous assessment
psa at screening ≥2 μg/l
serum testosterone concentration ≤50 ng/dl
serum albumin >2.5 g/dl

additional inclusion criteria for patients in ccs1477 plus abiraterone combination arm:

patients must have previously progressed on abiraterone treatment
patients whose last dose of abiraterone is greater than 6 months prior to start of study treatment will receive a 4-week run-in treatment with abiraterone to confirm refractoriness to abiraterone treatment

additional inclusion criteria for patients in ccs1477 plus enzalutamide combination arm:

patients must have previously progressed on enzalutamide treatment
patients whose last dose of enzalutamide is greater than 6 months prior to start of study treatment will receive a 4-week run-in treatment with enzalutamide to confirm refractoriness to enzalutamide treatment

additional inclusion criteria for patients in mutation arm:

advanced solid tumour with identification of markers which may indicate potential for response to p300/cbp inhibition. markers include loss of function mutations in crebbp, ep300 or arid1a, myc gene amplifications or rearrangements and androgen receptor (ar) gene amplifications or over-expression.

exclusion criteria:

intervention with any chemotherapy, investigational agents or other anti-cancer drugs within 14 days or 5 half-lives of the first dose
radiotherapy with a wide field of radiation or to more than 30% of the bone marrow within 4 weeks of the first dose of study treatment
major surgical procedure or significant traumatic injury within 4 weeks of the first dose of study treatment
strong inhibitors of cyp3a4 or cyp3a4 substrates with a narrow therapeutic range taken within 2 weeks of the first dose of study treatment
strong inducers of cyp3a4 within 4 weeks of the first dose of study treatment
statins; patients should discontinue statins prior to starting study treatment
any unresolved reversible toxicities from prior therapy >ctcae grade 1 at the time of starting study treatment
any evidence of severe or uncontrolled systemic diseases
any known uncontrolled inter-current illness
qtcf prolongation (> 480 msec).
primary brain tumours or known or suspected brain metastases.

additional exclusion criteria for patients in ccs1477 plus abiraterone combination arm:

clinically significant cardiac abnormalities

additional exclusion criteria for patients in ccs1477 plus enzalutamide combination arm:

history of seizures or other predisposing factors
use of substrates with a narrow therapeutic index metabolised by cyp2c9 or cyp2c19 within 2 weeks of the first dose of study treatment
clinically significant cardiac abnormalities",1,1,1,0,0,0,18.0,200.0,Breast,Pleura,0,0,All
183,183,183,953,NCT03570021,2023-05-17,estimation of the ability of prophylactic central compartment neck dissection to modify outcomes in low-risk differentiated thyroid cancer,estimation of the ability of prophylactic central compartment neck dissection to modify outcomes in low-risk differentiated thyroid cancer,ESTIMABL3,interventional,"prospective randomized open phase iii non-inferiority trial in ct1bt2n0 papillary thyroid carcinoma comparing: total thyroidectomy alone (experimental group) versus total thyroidectomy + prophylactic neck dissection pnd (reference group).

pre-registered patients will be randomized before surgery for tumors with class-6 cytology (bethesda) or in the operating room after confirmation of malignancy by frozen section analysis for tumors with class-5 cytology.","inclusion criteria:

thyroid nodule measuring 11-40 mm on ultrasound (ct1bt2)

and with fine-needle aspiration biopsy (fnab) cytology in favor of ""papillary thyroid carcinoma"" (type 6 according to the bethesda classification (appendix 2)
or with fnab cytology ""suspicious for malignancy"" (type 5 according to the bethesda classification). in this latter case, randomization will be performed if confirmation of papillary carcinoma on intraoperative frozen section analysis
cn0: absence of lymph nodes suspicious for malignancy on preoperative ultrasound performed by the center's designated radiologist according to a standardized report
absence of a medical contra indication to performing a total thyroidectomy with or without bilateral prophylactic neck dissection of the central compartment
women of childbearing potential should have a negative pregnancy test (serum or urine) before any radioiodine administration. sexually active patients must agree to use an effective method of contraception or to abstain from sexual activity during the study and for at least 6 months after last dose of radioiodine.
patient affiliated to a social security regimen or beneficiary of such regimen
patients age ≥ 18 years old, french-speaking
patients should understand, sign and date the written informed consent form prior to any protocol specific procedures. patients should be able and willing to comply with study visits.

exclusion criteria:

tumors > 40 mm (ct3) or ≤ 10 mm
tumors with extrathyroidal extension suspected or obvious on the pre-operative work-up or intra-operatively (ct3t4)
metastatic neck lymph nodes or suspicious neck nodes on preoperative ultrasound (cn1); for suspicious nodes, fnab cytology and thyroglobulin assay on the needle washout fluid will be performed
metastatic neck lymph nodes found during the thyroidectomy and confirmed with intra-operative frozen section analysis
medullary thyroid carcinoma on fnab cytology and/or with basal serum calcitonin >50 pg/ml
preoperative or intra-operative suspicion of non-papillary thyroid carcinoma or aggressive histopathological subtype or poorly differentiated carcinoma
distant metastases (m1) apparent pre-operatively (found due to symptoms or fortuitously; no specific pre-operative work-up will be performed, however, in accordance with current clinical practice)
recurrent nerve paralysis visualized on systematic pre-operative laryngoscopy and/or abnormal preoperative serum calcium
pregnant or breast feeding women
participation in another therapeutic clinical trial within one year from study entry
patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving its consent",1,0,0,1,0,0,18.0,200.0,Thyroid,Thyroid,0,1,All
184,184,184,955,NCT03571438,2020-01-16,evaluation of a promising new combination of protein kinase inhibitors on organotypic cultures of human renal tumors,evaluation of a promising new combination of protein kinase inhibitors on organotypic cultures of human renal tumors,COMBOREIN,interventional,"the investigators objective is to test the combination directly on organotypic cultures of tumors from patients after their excision in the department of urology and renal transplantation of the university hospital of grenoble and to compare their efficacy with that of currently selected treatments in the clinic.

the population targeted by the combination for use in clinical practice is patients with metastatic clear cell renal cell carcinoma.

current treatments for these patients are sunitinib, pazopanib and temsirolimus.","inclusion criteria:

major patient treated at the university hospital of grenoble for a renal tumor with suspected or confirmed malignancy.this includes non-metastatic patients undergoing renal lumpectomy, partial nephrectomy or total nephrectomy, as well as metastatic or locally advanced cancer patients undergoing cytoreductive surgery who are eligible for medical treatment at the same time

exclusion criteria:

contaminated patients with hiv and /or hbv (hepatitis b virus) and / or hcv (hepatitis c virus) positive serology.
absence or withdrawal of the informed consent of the patient.
tumors smaller than 2 cm on preoperative imaging",1,0,0,0,0,1,18.0,200.0,Kidney,Kidney,0,0,All
185,185,185,956,NCT03571633,2023-01-09,impact of pegfilgrastim on trastuzumab anti-tumor effect and adcc in operable her2+ breast cancer breast cancer,"a multicenter, randomized, open-label, phase ii trial aiming to evaluate the impact of pegfilgrastim on trastuzumab anti-tumor effect and adcc in operable her2 positive breast cancer patients",BREASTIMMU02,interventional,"first preclinical data suggest that pegfilgrastim could constitute a potent adjuvant for immunotherapy with mab possessing adcc/adcp properties as trastuzumab. combined treatment of pegfilgrastim and trastuzumab should translate into an increased rate of pathological clinical response. therefore the investigators' proposal is to evaluate the clinical and biological impact of pegfilgrastim in combination with trastuzumab + paclitaxel in her2-positive early stage breast cancer patients. breastimmune02 is a multicenter, randomized, open-label, phase ii trial. operable her2+ breast cancer patients previously treated with 4 cycles of standard adriamycine/cyclophosphamide (ac) chemotherapy will be randomized (1:1) to receive in the neoadjuvant setting:arm a: weekly paclitaxel + trastuzumab (every 3 weeks, q3w) + pegfilgrastim (q3w) versus arm b: weekly paclitaxel + trastuzumab (q3w).stratification criteria will be: cn0 versus cn1.","inclusion criteria:

female patients aged ≥ 18 years at time of inform consent signature.
histologically proven her2 positive breast cancer defined as 3+ staining intensity by immunohistochemistry (ihc) or a 2+ ihc staining intensity and her2 gene amplification by fish.note: her2 status will be determined as per institutional practice.
operable breast tumor with tumor size and staging: > 20 mm, cn0 or cn1, m0 before any ac or fec chemotherapy, and at least one measurable lesion ≥10 mm in longest diameter at inclusion according to recist 1.1.
no radiological sign of disease progression at time of randomisation.
patient previously treated by 4 cycles of ac or 3 to 4 cycles of fec without febrile neutropenia and without prior pegfilgrastim treatment.
availability of a representative formalin-fixed paraffin-embedded (ffpe) tumor specimen from initial diagnosis (i.e. an archival paraffin block is preferred; or at least 20 unstained slides) with its histological report.
eastern cooperative oncology group (ecog) performance status ≤ 2
adequate organ function as defined by the following lab tests (to be carried out within 7 days prior c1d1):bone marrow (absolute neutrophil count ≥ 1.5 x 109/l, platelet count > 100 x 109/l, (without transfusion within 21 days prior to c1d1), hemoglobin value ≥ 9 g/dl), renal function (calculated creatinine clearance by mdrd or ckd-epi >50 ml/min/1.73m2 or serum creatinine < 1.5uln), liver function (alanine aminotransferase (alt) and aspartate aminotransferase (ast) ≤ 3uln, total serum bilirubin ≤ 1.5 uln (except for patients with gilbert disease for whom a total serum bilirubin ≤3 uln is acceptable), coagulation (inr and aptt≤ 1.5 uln)
adequate cardiac function with mean resting corrected qt interval (qtc), calculated using fridericia's formula, ≤470ms obtained from 3 electrocardiograms (ecgs) and systolic blood pressure <160mmhg and diastolic blood pressure <100mmhg (hypertension controlled by standard medical treatment is allowed)
women of childbearing potential (entering the study after a confirmed menstrual period and who have a negative pregnancy test within 7 days before c1d1) must agree to use two methods of medically acceptable forms of contraception from the date of negative pregnancy test to 3 months after the last study drug intake
patients should be able and willing to comply with study visits and procedures as per protocol
patients should understand, sign, and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures performed.
patients must be covered by a medical insurance.

exclusion criteria:

patients with inflammatory breast cancer.
previous exposure to pegfilgrastim or trastuzumab. note: the use of filgrastim (non pegylated form only) is authorized prior to the randomisation.
patients requiring the concomitant use of any forbidden treatment including: any other anti-cancer treatments not listed in the protocol, including chemotherapy, radiotherapy, immunotherapy, targeted therapy or biologic therapy for cancer treatment, any investigational treatment.
any contra-indication to trastuzumab, paclitaxel, and pegfilgrastim respective spcs including:hypersensitivity to trastuzumab, murine proteins, or to any of the excipients listed in trastuzumab spc, severe dyspnea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy, hypersensitivity to pegfilgrastim or filgrastim, or to any of the excipients listed in spc, hereditary problems of fructose intolerance, hypersensitivity to paclitaxel or to any excipient, particularly macrogolglycerol ricinoleate, patients with history of or active cardiac disease including myocardial infarction (mi), angina pectoris requiring medical treatment, congestive heart failure nyha (new york heart association) class ≥ii, other cardiomyopathy, cardiac arrhythmia requiring medical treatment, clinically significant cardiac valvular disease, and hemodynamic effective pericardial effusion.
active secondary malignancy unless this malignancy is not expected to interfere with the evaluation of study endpoints and is approved by the sponsor. examples of the latter include basal or squamous cell carcinoma of the skin, in-situ carcinoma of the cervix. patients with a completely treated prior malignancy and no evidence of disease for ≥ 2 years are eligible.
pregnant or breast-feeding female patients.",1,0,1,0,0,0,18.0,200.0,Breast,Breast,0,0,Female
186,186,186,957,NCT03572621,2022-03-04,development and evaluation of a therapeutic education intervention in prostate cancer patients treated with radical prostatectomy to improve their sexuality,development and evaluation of a therapeutic education intervention in prostate cancer patients treated with radical prostatectomy to improve their sexuality,PRODUCAN,interventional,"prostate cancer is the most common cancer in france (54,000 cases in 2011). about 20,000 radical prostatectomies (pr) per year are performed. despite the progress of pr over the past 20 years, the rate of erectile dysfunction post pr varies between 30 and 90% and only 16% of operated men recover their pre-treatment erections.

there is currently no validated post-prostatectomy rehabilitation protocol. the associations of patients, including the national association of prostate cancer patients have a very strong demand for treatment of sexual problems after treatment.","inclusion criteria:

patients treated in urology consultation at the university hospital of lyon sud or edouard herriot:

aged over 18
presenting a cancerous pathology of the prostate having an indication of radical prostatectomy with or without preservation of the neurovascular strips.
affiliated to a social security scheme.
and having been informed and given informed consent to participation in the program.

exclusion criteria:

refusal of participation, signature of consent,
protected major patients, under guardianship or curators.
patients unable to understand the course of the study
patient with a documented history of cognitive or psychiatric disorders.",1,0,0,0,0,1,18.0,200.0,Prostate,Prostate,1,0,All
187,187,187,958,NCT03573596,2018-06-19,persistence of mr3 in chronic myeloid leukemia (cml) after a 2nd stop of tki treatment,persistence of major molecular remission in chronic myeloid leukemia after a second stop of tki treatment in patients who failed an initial stop attempt: a multicenter prospective trial,DASTOP2,interventional,"this study will enroll cml patients who have failed a first tki stopping attempt. after failure and at least a year of tki treatment, patients will proceed to dasatinib treatment for another 2 years. if mr4 or better is re-achieved and maintained for at least one year, patients will be eligible for a second stop. after verification of mr4, tki treatment will be stopped and patients followed in the same manner as after first stop. if mmr is lost (bcr-abl >0.1% (is)), tki treatment will once again be restarted.","inclusion criteria:

cml in chronical phase (cp) under tki treatment after failing a prior attempt to stop treatment within euro-ski or outside the study but according to euro-ski trial procedures. for the latter group this requires at least 3 years of tki treatment (first line or second line due to intolerance to first line) before first stop, and mr4 for at least one year before stopping.
treated with tki for at least one year after having failed a prior attempt to stop tki. previous tki can be any.
typical bcr/abl1 transcript (b3a2 and/or b2a2) must have been confirmed at diagnosis or later during the disease course.
18 years or older.

exclusion criteria:

previous hematological relapse after first stop of tki.
previous ap/bc at any time in the history of the disease.
restart of tki without loss of mmr after first stop
current participation in another clinical study.
previous or planned allogeneic stem cell transplantation.
patients with contra-indications to dasatinib therapy due to comorbidities.
subjects with acute hepatitis b virus (hbv) infections.
uncontrolled or significant cardiovascular disease.
pulmonary arterial hypertension.
pleural or pericardial effusions of any grade at study entry are excluded
history of significant bleeding disorder unrelated to cml
hypersensitivity to dasatinib and excipients of dasatinib tablets.",1,0,1,0,0,0,18.0,200.0,Pleura,Brain,0,0,All
188,188,188,960,NCT03576417,2023-09-21,a trial evaluating the addition of nivolumab to cisplatin-rt for treatment of cancers of the head and neck,a phase iii randomized trial of post-operative adjuvant nivolumab and concomitant chemo-radiotherapy in high-risk patients with resected squamous cell carcinoma of head and neck,NIVOPOSTOP,interventional,"the purpose of this study is to determine the efficacy of nivolumab + cisplatin-rt relative to standard of care (soc) cisplatin-rt alone, using the disease-free survival (dfs by investigator imaging assessment) as primary endpoint )","inclusion criteria:

age > 18 and < 75 years
performance status (ps) ecog 0-1 (appendix 2)
written informed consent
recording of alcohol consumption and smoking history
histologically proven squamous cell carcinoma of the head and neck from one or more of the following primary sites: oral cavity, oropharynx, hypopharynx or larynx
squamous cell carcinoma of the head and neck treated by primary surgery
histopathological classification: pstage iii or iv. however, oropharyngeal cancer pstage ii p16 positive with pt3n1 or pt4n1 and tobacco consumption ≥20 packs/year are eligible. (american joint committee on cancer 8th edition)
subject must have complete macroscopic resection.
subject must be free of disease
recovery from the surgical procedure allowing for cisplatin-radiotherapy
radiotherapy planned to start within 4 to 9 weeks after surgery. however, a maximum of 1 additional week could be considered in case of delay due to healing or logistical problem

patient/tumor carrying a high risk of relapse with:

extra-capsular extension (ece),
multiple peri-neural invasion
multiple nodal extension without ece (≥ 4 nodes)
positive margins (r1 or close margin ≤ 1 mm) r1 is microscopic residual disease and close margin is r0 with a minimum margin ≤ 1 mm in any direction.
adequate tumor specimen from archived or resected tissue available for pd-l1, tils and immune landscape and other biomarker evaluation
for oropharyngeal tumor, known p16 status (by ihc)

patient's ability to receive cisplatin 100 mg/m2 for 3 cycles:

creatinine cclearance (crcl) ≥ 60 ml/min (measured or calculated by cockcroft and gault method) or estimated glomerular filtration rate (egfr) ≥ 60 ml/min/1.73m2 (determined by ckdepi or mdrd method). the highest value should be considered if both are assessed.
absolute neutrophil count ≥1 500/mm3, platelets ≥100 000/mm3, haemoglobin ≥ 9 g/dl, aspartate transaminase (ast) and alanine transaminase (alt) less than 2.5 times the upper limit of the normal range (uln), total bilirubin ≤ 1.5 mg/dl(except gilbert syndrom: < 3.0 mg/dl).
peripheral neuropathy ≤ grade 1
no hearing loss (assessed clinically and confirmed by audiogram if doubtful)
cardiac function compatible with hyperhydration
no administration of prophylactic phenytoin
patients aged 71-74 years,must be fit according to geriatric evaluation

exclusion criteria:

nasopharyngeal, paranasal sinuses, nasal cavity tumours or thyroid cancers
squamous cell carcinoma involving cervical neck nodes with unknown primary site
metastatic disease
incomplete macroscopic resection (r2), as stated in the surgical report
known active viral infection human immunodeficiency virus (hiv), hepatitis b/c) or known history of positive test for hiv, active autoimmune disease and/or an active immunodeficiency or ongoing immunosuppressive therapy
active central nervous system disease
interstitial lung disease
active infection
any prior treatment for the current head and neck cancer other than primary surgery. this will include but is not limited to: prior tyrosine kinase inhibitors, any monoclonal antibody, induction chemotherapy, prior rt, or use of any investigational agent
concurrent treatment with any other systemic anti-cancer therapy that is not specified in the protocol
concomitant treatment with any drug on the prohibited medication list such as live vaccines. live vaccines administered more than 30 days before study entry are permitted
history of other malignancy within the last 3 years (exception of in situ carcinoma, thyroid papillary carcinoma, skin carcinomas, localized prostate carcinoma gleason 6 and in situ breast carcinoma)
pregnant, breastfeeding patients, and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in the protocol for the duration of the study and for at least 6 months after the last dose of cisplatin and 5 months after the last dose of nivolumab
male patients who are unwilling or unable to use contraception methods for the duration of the study and for at least 6 months after the last dose of cisplatin.
severe acute or chronic medical conditions including colitis, pneumonitis, pulmonary fibrosis, laboratory abnormalities or other significant disease which, in the judgment of the investigator, as a result of the medical interview, physical examinations, or screening investigations would make the patient inappropriate for entry into the trial
known hypersensitivity to study drugs
prior organ transplantation including allogenic stem-cell transplantation
clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ new york heart association classification class ii), or serious cardiac arrhythmia requiring medication
concurrent enrolment in another clinical trial using an investigational anti-cancer treatment within 28 days prior to the first dose of study treatment
subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness
any psychiatric condition (including active suicidal ideation), or psychological, or familial, or sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
individuals deprived of liberty or placed under the authority of a tutor.",1,0,0,1,0,0,18.0,74.0,Brain,Pleura,0,0,All
189,189,189,961,NCT03578367,2023-10-31,study of efficacy and safety of asciminib in combination with imatinib in patients with chronic myeloid leukemia in chronic phase (cml-cp),"a phase 2, multi-center, open-label, randomized study of oral asciminib added to imatinib versus continued imatinib versus switch to nilotinib in patients with cml-cp who have been previously treated with imatinib and have not achieved deep molecular response",,interventional,"to evaluate efficacy, safety and pharmacokinetic profile of asciminib 40mg+imatinib or asciminib 60mg+imatinib versus continued imatinib and versus nilotinib versus asciminib 80mg in pre-treated patients with chronic myeloid leukemia in chronic phase (cml-cp)","inclusion criteria:

male or female patients ≥ 18 years of age with a confirmed diagnosis of chronic myeloid leukemia in chronic phase (cml-cp).

minimum of one year (12 calendar months) treatment with imatinib first line for cml-cp (patients have to be on imatinib 300mg or 400 mg qd at randomization

for korea only:

(i)a minimum of one year (12 calendar months) of prior treatment with imatinib for patients with bcr-abl levels > 0.1%, ≤ 1% is at the time of randomization.

(ii) a minimum of two years (24 calendar months) of prior treatment with imatinib for patients with bcr-abl levels > 0.01%, ≤ 0.1% is at the time of randomization.

bcr-abl1 levels > 0.01% is (international scale) and ≤ 1% is at the time of randomization as confirmed with a central assessment at screening; patients must not have achieved deep molecular response (mr4 is) confirmed by 2 consecutive tests at any time during prior imatinib treatment. an isolated, single test result with bcr-abl1 levels < 0.01 % (mr4 is) is allowed, however, it should not have been observed within the 9 months prior to randomization

patient must meet the following laboratory values before randomization:

absolute neutrophil count ≥ 1.5 x 10e9/l
platelets ≥ 75 x 10e9/l
hemoglobin ≥ 9 g/dl
serum creatinine < 1.5 mg/dl
total bilirubin ≤ 1.5 x uln (upper limit of normal) except for patients with gilbert's syndrome who may only be included with total bilirubin ≤ 3.0 x uln
aspartate transaminase (ast) ≤ 3.0 x uln
alanine transaminase (alt) ≤ 3.0 x uln
alkaline phosphatase ≤ 2.5 x uln
serum lipase ≤ 1.5 x uln
patients must have the following laboratory values ≥ lower limit of normal or corrected to within normal limits with supplements prior to randomization: potassium increase of up to 6.0 mmol/l is acceptable if associated with creatinine clearance within normal limits ; calcium increase of up to 12.5 mg/dl or 3.1 mmol/l is acceptable if associated with creatinine clearance* within normal limits) ; magnesium increase up to 3.0 mg/dl or 1.23 mmol/l if associated with creatinine clearance within normal limits.

key exclusion criteria:

treatment failure according to european leukemia network (eln) criteria 2013 during imatinib treatment.
known second chronic phase of cml after previous progression to accelerated phase (ap)/blast crisis (bc).
previous treatment with any tyrosine kinese inhibitors (tkis) other than imatinib.

history or current diagnosis of ecg abnormalities indicating significant risk or safety for subjects participating in the study such as:

history of myocardial infarction, angina pectoris, coronary artery bypass graft within 6 months prior to randomization
concomitant clinically significant arrhythmias
resting qtcf ≥ 450 msec (male) or ≥ 460 msec (female) prior to randomization

long qt syndrome, family history of idiopathic sudden death or congenital long qt syndrome, or any of the following:

risk factors for torsades de pointes
concomitant medications with a ""known"" risk of torsades de pointes
inability to determine the qtcf interval
severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol (e.g. uncontrolled diabetes, active or uncontrolled infection, uncontrolled clinically significant hyperlipidemia and high serum amylase)
history of acute pancreatitis within 1 year prior to randomization or medical history of chronic pancreatitis; on-going acute liver disease or history of chronic liver disease
history of other active malignancy within 3 years prior to randomization with the exception of basal cell skin cancer, indolent prostate cancer and carcinoma in situ treated curatively.

other protocol defined inclusion/exclusion may apply.",1,0,1,0,0,0,18.0,200.0,Pleura,Brain,0,0,All
190,190,190,962,NCT03579394,2023-04-05,retarded surgery following neoadjuvant chemotherapy in advanced ovarian cancer,chrono - retarded surgery following neoadjuvant chemotherapy in advanced ovarian cancer,CHRONO,interventional,"the aim of chrono trial is to compare the dfs when surgery is performed after 3 courses of nact, or after 6 courses of nact, in a prospective multi institutional randomized setting,considering only patients initially unsuitable for primary surgery.","inclusion criteria:

female patients ≥18 years.
histologically confirmed epithelial ovarian cancer, fallopian tube carcinoma or primary peritoneal carcinoma, high grade serous or endometrioïd, with the exception of mucinous, clear cell and carcinosarcoma histologies.
performance status < 2 (see appendix 2).
documented international federation of gynecologic oncology (figo 2014, appendix 1) stage iiib-iiic-iva unsuitable for complete primary cytoreductive surgery (confirmed by open laparoscopy or by laparotomy [not mandatory for stage iva]).
patient must be judged resectable after 3 courses of neoadjuvant chemotherapy

adequate bone marrow, liver and renal function to receive chemotherapy and subsequently to undergo surgery:

white blood cells (wbc) >3x109/l, absolute neutrophil count (anc) ≥1,5x109/l, platelets (plt)

≥100x109/l, hemoglobin (hb) ≥9 g/dl,

serum creatinine <1.25 x upper normal limit (unl) or creatinine clearance ≥ 30 ml/min according to cockroft-gault formula or to local lab measurement, serum bilirubin <1.25 x unl, ast(sgot) and alt(sgpt) <2.5 x unl.
signed informed consent obtained prior to any study-specific procedures.
patient affiliated to, or a beneficiary of, a social security category

exclusion criteria:

mucinous, clear cell , carcinosarcoma and low grade serous carcinomahistologies.
synchronous or previous other malignancies within 3 years prior to starting study treatment, with the exception of adequately treated non-melanomatous skin cancer or carcinoma in situ (of the cervix or breast or other sites).
patients with brain metastases, seizure not controlled with standard medical therapy, or history of cerebrovascular accident (cva, stroke) or transient ischemic attack (tia) or subarachnoid hemorrhage before 6 months from the enrollment on this study.
any other concurrent medical conditions contraindicating surgery or chemotherapy that could compromise the adherence to the protocol (including but not limited to impaired cardiac function or clinically significant cardiac diseases, active or uncontrolled infections, hiv-positive patients on antiretroviral therapy, uncontrolled diabetes, cirrhosis, chronic active or persistent hepatitis, impaired respiratory function requiring oxygen-dependence, serious psychiatric disorders).
pregnant or breastfeeding women.",1,0,0,0,0,1,18.0,99.0,Other,Pleura,0,1,Female
191,191,191,963,NCT03580109,2023-05-10,spa therapy for upper or lower limb lymphoedema,spa therapy for upper or lower limb lymphoedema : a randomized and comparative study,THERMOEDEME,interventional,"thermoedeme is a comparative, controlled, randomized, multicenter and simple blinded (investigator) trial.

the aim of this study is to evaluate effects of spa therapy in phlebology with a therapeutic education program in daily life of patients suffering lymphoedema.","inclusion criteria:

18 years old and older
available for a spa treatment (phlebology indication) during 18 days and a follow up period of 15 months
with permanent lymphoedema of the upper or lower limb (2 ou 3 stade of international society for lymphology scale)
voluntary to participate to the study, informed consent form signed after appropriate information
affiliation to the social security system or equivalent

exclusion criteria:

cancer undergoing chemotherapy and radiotherapy treatment in primary phase
the baseline score of lms27 or lymqol-leg > 79
pain of upper limb linked with a radical plexitis
contra-indication of spa treatment (cancer in progress, psychiatrics disorders, immunodeficiency)
erysipelas case history in the last 6 months or pachyderma and lymphangiectasia
no previous spa treatment for upper limb lymphoedema during the spa year
risk of intensive treatment in the next 6 months
subject participating to an other clinical study interventional
pregnancy, parturient or breast feeding",1,0,0,0,0,1,18.0,200.0,Pleura,Pleura,0,0,Female
192,192,192,968,NCT03584334,2023-04-12,18fdg pet for early identification of tumor exhaust for immunotherapy in patients with locally advanced or metastatic non-small cell bronchopulmonary carcinoma or melanoma,cohort study evaluating 18fdg pet for early identification of tumor exhaust for immunotherapy in patients with locally advanced or metastatic non-small cell bronchopulmonary carcinoma or melanoma,FDG-IMMUN,interventional,"the hypothesis of this diagnostic performance study is that, for patients treated for immunotherapy-treated melanoma or nsclc, some metabolic parameters of the 18fdg dual-point pet scan distinguish inflammatory pseudo-progression from tumor progression true and thus improve the evaluation of tumor response to immunotherapy","inclusion criteria:

age > or = 18 years,
patients with unresectable melanoma or histologically proven, metastatic or locally advanced nsclc,
indication of an immunotherapy treatment with nivolumab or pembrolizumab validated in multidisciplinary consultation team and prescribed as part of their marketing authorization, in first or second line of treatment,
performance status 0 to 2,
female subjects of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required,
female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 6 months after the last dose of study medication. subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year,
male subjects should agree to use an adequate method of contraception or abstain from heterosexual activity starting with the first dose of study therapy through 6 months after the last dose of study therapy,
patient willing and able to provide written informed consent/assent for the trial,
patient affiliated with a health insurance system.

exclusion criteria:

age < 18 years,
contraindication to performing 18fdg pet scans: severe claustrophobia, unbalanced diabetes during pet examinations (fasting capillary blood glucose ≥ 11 mmol),
any participation in other biomedical studies related to the drug, medical devices or imaging techniques is prohibited except biomedical studies called overstudies (in case of doubt or questions about the patient's participation in a other clinical study, please contact the sponsor),
contraindication to nivolumab or pembrolizumab treatment,
patient with metastatic disease,
history of thoracic irradiation or near / in the thoracic irradiation field,
patient who refuses to participate in the study or unable to agree,
patient currently receiving one or more treatments described in section 6.9 of the protocol,
contraindication to nivolumab or pembrolizumab treatment,
people particularly vulnerable as defined in articles l.1121-5 to -8 of the french healthcare code, including: person deprived of freedom by an administrative or judicial decision, adult being the object of a legal protection measure or outside a state to express their consent, pregnant or breastfeeding women.",1,0,0,0,0,1,18.0,200.0,Lung,Lung,1,0,All
193,193,193,970,NCT03585465,2023-06-30,nivolumab in combination with metronomic chemotherapy in paediatrics refractory / relapsing solid tumors,metro-pd1: a phase i/ii trial evaluating anti-pd1 (nivolumab) in combination with metronomic chemotherapy in children and teenagers with refractory / relapsing solid tumors,,interventional,"the study is a two-stage trial:

first stage (closed - 16 patients recruited in france):

phase i feasibility trial to evaluate the safety of the combination of nivolumab + metronomic chemotherapy considering three possible metronomic chemotherapy regimens

second stage (opened - 86 patients expected in france and belgium):

phase ii randomized controlled balanced 1:1 open-label trial comparing the efficacy of the metronomic chemotherapy regimen selected at the end of the previous stage (arm c: cyclophosphamide, capecitabine, vinblastine), with or without nivolumab.

""trans-metropd1"" ancillary sub-study is partially implemented since april 2022, and proposed to patients participating to second stage","inclusion criteria:

histologically proven diagnosis of solid malignant tumor. confirmed progressive or refractory disease despite standard therapy or for which no effective standard therapy exists
histologically proven diagnosis of: embryonal brain tumor ; ependymoma ; low-grade glioma (lgg) ; high-grade glioma (hgg) except diffuse intrinsic pontine glioma (dipg) supratentorial diffuse midline glioma k27m mutated are eligible ; rhabdomyosarcoma ; neuroblastoma ; ewing sarcoma ; and other solid tumors and after approval from coordinators (except dipg, osteosarcoma, lymphoma), and confirmed progressive or refractory disease despite standard therapy or for which no effective standard therapy exists (this criterion is applicable to stage 2 only)
male and female subjects < 18 years of age at inclusion; patients of 18 years and older may be included after discussion with the sponsor if they had a pediatric recurrent/refractory malignancy diagnosed before the age of 18.

evaluable or measurable disease as defined by adequate standard imaging criteria for each patient's tumor type (see corresponding appendices for definition of evaluable and/or measurable lesions):

rano criteria for patients with high grade glioma (hgg), who are eligible at stage 1 only
rapno criteria for patients with low grade glioma
who for other cerebral tumors
inrc criteria for patients with neuroblastoma (nb),
recist v1.1 for tumors other than cerebral tumors and neuroblastoma
performance status: karnofsky performance status (for patients >12 years of age) or lansky play score (for patients ≤12 years of age) ≥ 70%. patients who are unable to walk because of paralysis or stable neurological disability, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
life expectancy ≥ 3 months
adequate organ function:

hematologic criteria

peripheral absolute neutrophil count (anc) ≥ 1500/mm3 (unsupported)
white blood cells count ≥ 2500/mm3
platelet count ≥ 100,000/mm3 (unsupported)
hemoglobin ≥ 8.0 g/dl (transfusion is allowed)

cardiac function

shortening fraction (sf) >29% (>35% for children < 3 years) and left ventricular ejection fraction (lvef) ≥50% at baseline, as determined by echocardiography (mandatory only for patients who have received cardiotoxic therapy).
absence of qtc prolongation (qtc > 450 msec on baseline ecg, using the fridericia correction [qtcf formula]) or other clinically significant ventricular or atrial arrhythmia.

renal and hepatic function

serum creatinine < 1.5 x upper limit of normal (uln) for age
total bilirubin < 1.5 x uln,
alanine aminotransferase (alt)/serum glutamic pyruvic transaminase (sgpt) < 3 x uln;
aspartate aminotransferase (ast)/serum glutamic oxaloacetic transaminase/sgot < 3 x uln
able to comply with scheduled follow-up and with management of toxicity.
females of child bearing potential must have a negative serum or urine pregnancy test within 7 days prior to initiation of treatment.
sexually active patients must agree to use adequate and appropriate contraception while on study drug and for 6 months after stopping the study drug for young men, and for 12 months after stopping the study drug for young women
patients on stable doses of corticosteroids (≤0.25 mg/kg prednisolone or equivalent) for at least 7 days prior to receiving study drug may be included.
written informed consent from parents/legal representative, patient, and age-appropriate assent before any study-specific screening procedures are conducted according to local, regional or national guidelines.
patient affiliated to a social security regimen or beneficiary of the same according to local requirements.
patients can have received prior treatment with antipd1 or antipdl1 if at least sd for 6 months or pr or cr was obtained.
patients with a known partial deficiency of dihydro-pyrimidine-deshydrogenase (dpd) activity are eligible, and must have an uracilemia value ≥16ng/ml and <150ng/ml
adult patient (or parents/legal representatives if patient is minor) understand the preparation process of soluble capecitabine, and are able to reconstitute oral solution of capecitabine at home

exclusion criteria:

leukemia
diagnosis of lymphoma, diffuse intrinsic pontine glioma or osteosarcoma (for stage 2 only)
patients with symptomatic central nervous system (cns) metastases who are neurologically unstable or require increasing doses of corticosteroids or local cns-directed therapy to control their cns disease.
patients requiring high doses of corticosteroids >0.25mg/kg prednisolone or equivalent) or increasing doses of corticosteroids during the 7 days prior to receiving study drug.

for patients with cns tumor:

o evidence of > grade 1 recent cns hemorrhage on the baseline mri scan.

o participants with bulky tumor on imaging are ineligible; bulky tumor is defined as: i) tumor with any evidence of uncal herniation or severe midline shift ii) tumor with diameter of > 6 cm in one dimension on contrast-enhanced mri iii) tumor that in the opinion of the investigator, shows significant mass effect

impairment of gastrointestinal (gi) function or gi disease that may significantly alter drug absorption of oral drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome).
clinically significant, uncontrolled heart disease (including history of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months of screening)
active viral hepatitis or known human immunodeficiency virus (hiv) infection or any other uncontrolled infection.
active autoimmune disease requiring immunosuppressive treatment
known congenital immunodeficiency
presence of any nci-ctcae v5 grade ≥ 2 treatment-related extra-hematological toxicity with the exception of alopecia, ototoxicity or peripheral neuropathy.
systemic anticancer therapy within 21 days of the first study dose or 5 times its half-life, whichever is less, 6 weeks in case of nitrosourea.
no clinical benefit with previous antipd1 or antipdl1 treatment (sd during a period inferior to 6 months, or pd).
previous myeloablative therapy with autologous hematopoietic stem cell rescue within 8 weeks of the first study drug dose.
allogeneic stem cell transplant within 3 months prior to the first study drug dose. patients receiving any agent to treat or prevent graft-versus host disease (gvhd) post bone marrow transplant are not eligible for this trial.
radiotherapy (non-palliative) within 21 days prior to the first dose of drug (or within 6 weeks for therapeutic doses of mibg or craniospinal irradiation).
major surgery within 21 days of the first dose. gastrostomy, ventriculo-peritoneal shunt, endoscopic ventriculostomy, tumor biopsy and insertion of central venous access devices are not considered major surgery, but for these procedures, a 48 hour interval must be maintained before the first dose of the investigational drug is administered.
currently taking medications with a known risk of prolonging the qt interval or inducing torsades de pointes.
known hypersensitivity to any study drug or component of the formulation.
absence of effective contraception in patients of childbearing age
pregnant or nursing (lactating) females.
vaccination with live, attenuated vaccines within 4 weeks of the first dose of the study drugs except inactivated vaccines.
patient with a known complete absence of dpd activity; it is known that patients carrying some homozygous or heterozygous mutations of dpyd responsible for the complete or almost complete absence of enzymatic activity of dpd, are exposed to a maximum risk of life-threatening or fatal toxicity ; patients with a complete deficiency of dpd activity (uracilemia ≥150ng/ml) should not be included in the trial neither treated with capecitabine
patients with galactose intolerance, lapp lactase deficiency or glucose or galactose malabsorption syndrome (rare hereditary diseases)
acute urinary tract infection, pre-existing hemorrhagic cystitis; obstruction of the urinary tract
history of organ transplant
severe infections requiring parenteral antibiotic therapy
active tuberculosis
history of interstitial lung disease

inclusion criteria for trans-metropd1

patient or parents/legal representative has/have given written informed consent to participate to all or part of trans-metropd1 study
if patient or parents/legal representative agrees to participate to the dosage of circulating progastrin only, patient body weight must be ≥ 8 kg to allow sample collection while respecting blood volume limits in paediatric population
if patient or parents/legal representative agrees to participate to immune cells count only, or both immune cells count and dosage of circulating progastrin, patient body weight must be ≥ 54 kg to allow sample collection while respecting blood volume limits in paediatric population",1,1,1,0,0,0,0.0,18.0,Brain,Pleura,0,0,All
194,194,194,972,NCT03590171,2023-02-09,international study for treatment of high risk childhood relapsed all 2010,"international study for treatment of high risk childhood relapsed all 2010 a randomized phase ii study conducted by the resistant disease committee of the international berlin, frankfurt, münster (bfm) study group",,interventional,the main goal of this study is to improve the outcome of children and adolescents with acute lymphoblastic leukemia with high risk first relapse by optimization of treatment strategies within a large international trial and the integration of new agents.,"inclusion criteria:

morphologically confirmed diagnosis of 1st relapsed precursor b-cell or t-cell all
children less than 18 years of age at date of inclusion into the study
meeting hr criteria any bm relapse, early/very early isolated bm relapse, very early isolated/combined extramedullary relapse)
patient enrolled in a participating centre
written informed consent
start of treatment falling into the study period
no participation in other clinical trials 30 day prior to study enrolment that interfere with this protocol, except trials for primary all

exclusion criteria:

breakpoint cluster region-abelson (bcr-abl)/ t(9;22) positive all
pregnancy or positive pregnancy test (urine sample positive for β-humane choriongonadotropin (hcg) > 10 u/l)
sexually active adolescents not willing to use highly effective contraceptive method (pearl index <1) until 12 months after end of anti-leukemic therapy
breast feeding
relapse post allogeneic stem-cell transplantation
neuropathy > ii°
the whole protocol or essential parts are declined either by patient himself/herself or the respective legal guardian
objection to the study participation by a minor patient, able to object
any patient being dependent on the investigator
no consent is given for saving and propagation of pseudonymized medical data for study reasons
severe concomitant disease that does not allow treatment according to the protocol at the investigator's discretion (e.g. malformation syndromes, cardiac malformations, metabolic disorders)
subjects unwilling or unable to comply with the study procedures
subjects who are legally detained in an official institute",1,0,1,0,0,0,0.0,17.0,Brain,Brain,0,1,All
195,195,195,977,NCT03595787,2023-02-13,coaching and prehabilitation: faisability study in patients with acute myeloid leukemia and myelodysplastic syndrome,feasibility study of tripartite prehabilitation of patients with acute myeloid leukaemia and high-risk myelodysplastic syndromes during intensive chemotherapy before allogenic haematopoietic stem cell transplantation: the cohabilit protocol,COHABILIT,interventional,"this faisability study aims to evaluate the adhesion of the patient to a multidisciplinary program (adapted physical activity, coaching and nutrition)","inclusion criteria:

diagnosis of acute myeloid leukemia or high-risk myelodysplastic syndrome
age between 18 and 70 years
eligible for an intensive chemotherapy
eligible for allograft
able to answer a questionnaire

exclusion criteria:

diagnosis of acute promyelocytic leukemia
palliative treatment
contraindication to moderate physical activity
performans status 4, unless it is related to the disease
patient who does not understand french
patient unable to use a smartphone
patient deprived of liberty or placed under the authority of a tutor,
patient considered socially or psychologically unable to comply with the treatment and the required medical follow-up.",1,0,0,0,0,1,18.0,70.0,Pleura,Brain,0,0,All
196,196,196,982,NCT03597321,2018-07-24,early prophylactic donor lymphocyte infusion after allo-hsct for patients with aml,comparative phase ii trial of early prophylactic donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation for patients with acute myeloid leukemia,ELIT-AML01,interventional,"allogeneic hematopoietic stem cell transplantation (allo-hsct) is a curative option for patients with acute myeloid leukemia (aml). however, transplantation related toxicity and mortality as well as the existence of hla identical sibling donor represent major limitations. over the 20 past years, the development of reduced intensity conditioning (ric) regimen and the use of alternative donors allowed extending the possibility of allo-hsct for aml, with decreased toxicity and mortality. this invited to propose this strategy to more advanced patients, making that aml recurrence has become one of the main issues after allo-hsct. thus, to develop prophylactic and preemptive strategies to minimize disease recurrence after allo-hsct is now the main challenge in the field. among cellular and/or pharmacological treatments after allo-hsct, donor lymphocyte infusion (dli) is probably one of the most commonly used treatments after allo-hsct. indeed, dli were reported as a potential efficient immunotherapy more than 20 years ago for the treatment of patients with leukemia relapsing after allo-hsct. however, most of experiences were reported in the setting of relapse after allo-hsct and no prospective evaluation of prophylactic dli is available so far. thus no strong recommendation for the use of dli after allo-hsct can be made. our study proposal would like to assess the question of prophylactic dli efficacy, as a proof of concept of early immune intervention after allo-hsct. the investigators, therefore, designed a prospective multicenter randomized trial evaluating the impact of early dli on outcome after allo-hsct for aml.","inclusion criteria:

aml in hematological complete remission at the time of inclusion
patient age from 18 to 70.
able to comply with the protocol.
written informed consent.
allogeneic stem cell transplantation from any donor except cord blood.
unmanipulated bone marrow or peripheral blood stem cells as graft source are allowed
ongoing gvhd prophylaxis using cyclosporin a at the time of inclusion.

exclusion criteria:

presence or history of grade 2 to 4 acute gvhd.
no hematological cr of aml at the time of inclusion. cr patients positive with molecular or phenotypic minimal residual disease (mrd) can be included.
pregnancy/breast feeding.
patient considered socially or psychologically unable to comply with the treatment and the required medical follow-up.
concomitant uncontrolled disease and/or organ dysfunction (infection, severe heart, renal, respiratory or hepatic failure…).
primary or secondary graft failure.
previous solid organ allogeneic transplantation.",0,0,1,0,0,0,18.0,70.0,Pleura,Pleura,0,0,All
197,197,197,984,NCT03598946,2022-07-13,urinary human papilloma virus test in the general population in brittany,"evaluation of the impact of a screening strategy based on a home urinary test in non-respondent women on a first invitation to papillomavirus screening, on the participation rate compared to a uterine cervix smear screening, with taking into account the socio-economic level, during the organized screening for cervical cancer in brittany",PapU-Access,interventional,"this is a population-based, prospective, multicenter and open-label study. 12,500 female non-respondents to the uterine cervix smear from 30 to 65 years of age in the context of the organized cervical cancer screening of the uterus, in the 4 breton departments, will be proposed after stratification by age and socio-economic level at the revival of the cervical cancer of the uterus screening by the structure of management of rennes, an invitation to the human papilloma virus urine test thanks to the sampling kit sent to the home. it is planned a revival by simple mail after 4 months in one woman out of two who did not respond to this invitation to assess the impact of a recovery. this group represents about 5% of the eligible population in brittany. the specimen will be sent by post with the signed consent and a questionnaire to the hospital of brest in virology laboratory for the detection of human papilloma virus dna (qpcr) in the urine (hpu test) and typing (lipa). in the case of a positive human papilloma virus test, the woman being tested has a strong incentive to do the cervical cancer of the uterus with her doctor or midwife. in the case of abnormal smear, follow-up continues according to national recommendations to a gynecologist. all the data is collected on a software from the links company, with the networking of the 4 breton centers, the virology laboratory, and the anatomy-cytology-pathology laboratories in brittany; this collection will allow after extraction, a statistical analysis of the data. the analysis of the participation rate in this new screening, for each level of the socio-economic level, will allow a comparison with the participation in smear's revival of organized screening, between women's groups according to the socio-economic level of their residential place.

the project will take place over 24 months in 3 phases:

d0-m6: pre-inclusion phase with implementation of the protocol (regulatory procedures, production of newsletters, consent, questionnaire, preparation of urine collection kits, postal validation).
m6-m18: inclusion phase with start of the study, sending invitations and inclusion, human papillomavirus urinary testing and uterine cervix smear monitoring.
m18-m24: post-inclusion phase with assessment of the inclusions on the 4 breton departments, verification and analysis of the data according to the socio-economic level, recovery of the uterine cervix smear stimulus data, realization of the statistical analyzes and budget impact analysis, communications and publications.","inclusion criteria:

women from 30 to 65 years old who did not do uterine cervix smear and who live in brittany

exclusion criteria:

women under 30 years or over 65 years
women of 30-65 years who have responded to the uterine cervix smear invitation
women who have had an uterine cervix smear raise
women who have already had an uterine cervix smear within 3 years
women who had a total hysterectomy",1,0,0,0,0,1,30.0,65.0,Vulva,Bladder,0,1,Female
198,198,198,987,NCT03599960,2022-05-31,combination chemotherapy in patients with newly diagnosed bpdcn,"combination chemotherapy (methotrexate, l-asparaginase, idarubicin and dexamethasone) in patients with newly diagnosed blastic plasmacytoid dendritic cell neoplasm (bpdcn)",LpDessai,interventional,"patients with suspected bpdcn and meeting eligibility criteria will be enrolled in the study. first, bpdcn diagnosis will be confirmed by anatomic pathology (dr petrella t, montreal) and cytologic plus immunophenotyping analysis (pr garnache ottou f, umr1098 besancon). patients will then receive three 21 days cycles of a combination of chemotherapy (ida/metho/l-asp/dex), followed by an evaluation. patients with complete response (cr) or complete response with incomplete bone marrow recovery (cri) will undergo an allo- or auto-sct and those who are not eligible to the transplantation will have successive 28 days cycles of chemotherapy (metho/l-asp/dex). patients who did not respond to the treatment will be treated by physicians. all patients will be followed for 24 months.","inclusion criteria:

newly diagnosed bpdcn established by a blood or bone marrow immunophenotypic diagnosis by flow cytometric and/or by the anatomic pathology study of a skin biopsy using validated diagnostic criteria (swerdlow sh ce et al., world health organisation classification of tumors, 2008; garnache-ottou et al., 2009; angelot et al., 2012; julia et al., 2014) or patients with confirmed isolated skin lesion.
18 years of age or older
no prior cytotoxic therapy except <2 week of corticosteroids or hydroxyurea
ecog ≤2
written informed consent
affiliation to the french social security scheme

exclusion criteria:

cardiac contra-indication to anthracyclines: cardiac dysfunction events (nyha grade 3 or 4 and/or lvef<50%)

hepatocellular abnormalities except if considered related to the bpdcn:

asat (sgot) and/or alat (sgpt) > 5 x uln
total bilirubin ≥ 2.5 x uln
creatinine level >1.5x uln or creatinine clearance (mdrd)<50 ml/mn
prior thrombotic event
active hepatitis b or c virus infection
hiv positive
serious medical or psychiatric illness that could interfere with the completion of treatment
known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
pregnant and lactating female patients
patients diagnosed with or treated for another malignancy within 2 years before study enrollment or with residual disease (basal cell carcinoma or cervical carcinoma in situ patients may be enrolled if they have undergone complete resection)",1,0,1,0,0,0,18.0,200.0,Breast,Brain,0,1,All
199,199,199,990,NCT03601078,2023-09-29,an efficacy and safety study of bb2121 in subjects with relapsed and refractory multiple myeloma and in subjects with high-risk multiple myeloma,"a phase 2, multi-cohort, open-label, multicenter study to evaluate the efficacy and safety of bb2121 in subjects with relapsed and refractory multiple myeloma and in subjects with clinical high-risk multiple myeloma (karmma-2)",KarMMa-2,interventional,"this study is a multi-cohort, open-label, multicenter phase 2 study to evaluate the efficacy and safety of bb2121 in subjects with relapsed and refractory mm (cohort 1), in subjects with mm having progressed within 18 months of initial treatment including autologous stem cell transplantation (asct) (cohort 2a), or without asct (cohort 2b) or, in subjects with inadequate response post asct during initial treatment (cohort 2c). approximately 235 subjects will be enrolled into one of three cohorts. cohort 1 will enroll approximately 97 rrmm subjects with ≥ 3 prior anti-myeloma treatment regimens. cohort 2a will enroll approximately 39 mm subjects, with 1 prior anti-myeloma therapy including asct and with early relapse. cohort 2b will enroll approximately 39 mm subjects with 1 prior anti-myeloma therapy not including asct and with early relapse. cohort 2c will enroll approximately 30 mm subjects with inadequate response to asct during their initial anti-myeloma therapy. the cohorts will start in parallel and independently. cohort 3 will enroll approximately 30 newly diagnosed multiple myeloma (ndmm) participants with suboptimal response to asct.","inclusion criteria:

subjects must satisfy the following criteria to be enrolled in the study:

subject is ≥ 18 years of age at the time of signing the informed consent form (icf)

for cohorts 1 and 2 only, participant has measurable disease, defined as:

m-protein (serum protein electrophoresis [spep] or urine protein electrophoresis [upep]): spep ≥ 0.5 g/dl or upep ≥ 200 mg/24 hours and/or
light chain mm without measurable disease in the serum or urine: serum immunoglobulin free light chain ≥ 10 mg/dl and abnormal serum immunoglobulin kappa lambda free light chain ratio

subjects with one of the following cohort specific requirements:

cohort 1 rrmm subjects with ≥ 3 prior anti-myeloma treatment regimens:

subject must have received at least 3 prior anti-myeloma treatment regimens. note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single regimen
subject must have undergone at least 2 consecutive cycles of treatment for each regimen, unless pd was the best response to the regimen
subject must have received prior treatment with a proteasome inhibitor, an immunomodulatory agent and an anti-cd38 antibody
subject has evidence of pd on or within 60 days of the most recent prior treatment regimen
subject achieved a response (minimal response [mr] or better) to at least 1 prior treatment regimen

cohort 2 subjects with 1 prior anti-myeloma treatment regimen:

subject must have received only 1 prior anti-myeloma treatment regimen. note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single regimen
subject must have the following hr factors:
early relapse defined as:

cohort 2a: pd < 18 months since date of start of initial therapy. initial therapy must contain induction, asct (single or tandem) and lenalidomide containing maintenance.

cohort 2b: pd < 18 months since date of start or initial therapy which must contain at minimum, a proteasome inhibitor, an immunomodulatory agent and dexamethasone cohort 2c: subject must have received minimum 3 cycles of induction therapy which must contain at minimum, a proteasome inhibitor, an immunomodulatory agent and dexamethasone. subjects must have had asct (single or tandem and < vgpr (excluding pd) at first assessment between 70 to 110 days after last asct, with initial therapy without consolidation and maintenance.

cohort 3 participants with newly diagnosed mm (ndmm) who received only induction and asct, without subsequent consolidation or maintenance cohort 3

must have received 4 to 6 cycles of induction therapy which must contain at minimum, a proteasome inhibitor and an immunomodulatory agent and must have had single asct within 6 months prior to consent
must have achieved documented pr or vgpr at first post-asct assessment approximately 100 days after asct and this response must be maintained at screening
per investigator's assessment, subject must be a candidate for single-agent lenalidomide maintenance
subject must have eastern cooperative oncology group (ecog) performance status ≤ 1
subject must have recovery to grade 1 or baseline of any non-hematologic toxicities due to prior treatments, excluding alopecia and grade 2 neuropathy

exclusion criteria:

the presence of any of the following will exclude a subject from enrollment:

subject used any investigational agents within 14 days prior to leukapheresis or, for cohort 3, within 14 days prior to consent

subject received any of the following within the last 14 days prior to leukapheresis or, for cohort 3, within 14 days prior to consent:

plasmapheresis
major surgery (as defined by the investigator)
radiation therapy other than local therapy for myeloma associated bone lesions
use of any systemic anti-myeloma drug therapy
subject with known central nervous system involvement with myeloma
subject has clinical evidence of pulmonary leukostasis and disseminated intravascular coagulation
history or presence of clinically relevant central nervous system (cns) pathology
subject with active or history of plasma cell leukemia, waldenstrom's macroglobulinemia, poems syndrome, or clinically significant amyloidosis
inadequate organ function subject with a history of class iii or iv congestive heart failure (chf) or severe nonischemic cardiomyopathy, unstable or poorly controlled angina, myocardial infarction, or ventricular arrhythmia within the previous 6 months prior to starting study treatment
ongoing treatment with chronic immunosuppressants
previous history of an allogeneic hematopoietic stem cell transplantation or treatment with any gene therapy-based therapeutic for cancer or investigational cellular therapy for cancer or bcma targeted therapy
subject has received asct within 12 weeks prior to leukapheresis
subject has history of primary immunodeficiency
subject is positive for human immunodeficiency virus (hiv-1), chronic or active hepatitis b or active hepatitis a or c
subject has uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment
subject with prior history of malignancies, other than mm, unless the subject has been free of the disease for ≥ 5 years
pregnant or lactating women
subject with known hypersensitivity to any component of bb2121 product, cyclophosphamide, fludarabine, and/or tocilizumab
prior history of deep venous thrombosis (dvt) or pulmonary embolus (pe) within 6 months prior to consent (for cohort 3)",1,0,1,0,0,0,18.0,200.0,Brain,Brain,0,0,All
200,200,200,997,NCT03606837,2022-12-16,68ga-rm2 compared to 68ga-psma-617 pet/ct for intermediate risk prostate cancer imaging,"exploratory, single-institution study, comparing 68ga-rm2 pet/ct versus 68ga-psma-617 pet/ct in patients diagnosed with intermediate risk prostate cancer candidates for radical prostatectomy",PROSTATEP,interventional,"patients with primary intermediate risk prostate cancer for whom radical prostatectomy is indicated, will be invited to participate to the present study.

positron emission tomography coupled with scanner (pet-ct) using a radiotracer : 68ga-rm2 and positron emission tomography coupled with scanner (pet-ct) using another radiotracer : 68ga-psma-617, will be scheduled.","inclusion criteria:

15 patients divided in :

7 patients with favourable intermediate risk prostate cancer (ct2b or gleason score 7 (3+4) or psa value 10-20 ng/ml, briganti 5-20%,)
8 patients with unfavourable intermediate risk prostate cancer (ct2b or gleason score 7 (4+3) or psa value 10-20 ng/ml, briganti 5-20%,)
who are candidate for radical prostatectomy after discussion in multidisciplinary committee
covered by the national health insurance system
with freely written informed consent obtained

exclusion criteria:

any kind of previous treatment for prostate cancer (hormonal treatment, ebrt, brachytherapy, cryotherapy, etc…);
patient with prostate cancer not candidate for radical prostatectomy and/or unable to benefit from surgery
freedom privated patient
patient under legal protection or unable to express its own consent
known contraindication to radiopharmaceuticals and / or excipients ……",1,0,1,0,0,0,18.0,200.0,Prostate,Prostate,0,0,Male