araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 86-year-old female with melanoma; genetic feature: high tumor mutational burden

Clinical trial: A Study of MEK162 and AMG 479 in Patients With Selected Solid Tumors

Summary: This is a multi-center, open-label, phase Ib/II study. First, the aim of the phase Ib part is to estimate the MTD(s) and/or to identify the recommended phase II dose(s) (RP2D) for the combination of MEK162 and AMG 479 (ganitumab), followed by the phase II part to assess the clinical efficacy and to further assess the safety of the combination in selected patient populations. The dose escalation part of the study will be guided by a Bayesian Logistic Regression Model (BLRM). At least 18 patients are expected to be enrolled in the dose escalation part.
  Following MTD/ RP2D declaration, patients will be enrolled in three phase II arms to assess efficacy of the combination as well as to better understand the safety, tolerability, PK, antibody concentrations and PD of the combination at MTD/RP2D. Phase II arm 1 will consist of approximately 25 patients with KRAS-mutant colorectal adenocarcinoma. Phase II arm 2 will consist of approximately 20 patients with metastatic pancreatic adenocarcinoma. Phase II arm 3 will consist of approximately 28 patients with mutant BRAFV600 melanoma.
  Patients will be treated until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurs first. All patients will be followed up - at minimum patients must complete the safety follow-up assessments 30 days after the last dose of the study treatment.


Eligibility: Inclusion Criteria:
  -  Patients aged ≥ 18 years
  -  Patients with advanced solid tumors (CRC, melanoma) with documented somatic KRAS or BRAFV600 mutations in tumor tissue. Patients with metastatic pancreatic adenocarcinoma may be enrolled irrespectively of KRAS or BRAFV600 mutational status.
  -  Patients must have relapsed or progressed following standard therapy or patients for whom no standard anticancer therapy exists.
  -  Measurable disease as determined by RECIST v1.1. World Health Organization (WHO) Performance Status (PS) ≤ 2.
  -  Adequate organ function
  -  Negative serum pregnancy test
  Exclusion Criteria:
  -  Prior therapy with MEK- or IGF-1R- inhibitor
  -  History or current evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO) or retinal degenerative disease
  -  Patients with known history of severe infusion reactions to monoclonal antibodies
  -  Patients with primary CNS tumor or CNS tumor involvement
  -  History of thromboembolic event requiring full-dose anticoagulation therapy
  -  Clinically significant cardiac disease
  -  History of another malignancy within 2 years
  -  Pregnant or nursing (lactating) women
  Other protocol-defined inclusion/exclusion criteria may apply

Relevance to patient case: not relevant
Patient case: 86-year-old female with melanoma; genetic feature: high tumor mutational burden

Clinical trial: Study of Circulating Tumor Cells Before and After Treatment in Patients With Metastatic Melanoma

Summary: Circulating tumor cells (CTC) are the subject of increasing interest in clinical oncology as a prognostic factor and predictor of therapeutic response. The detection of CTC by immunomagnetic method has proved its reliability and its usefulness for monitoring breast cancer, colon and prostate in the metastatic and immunomagnetic detection system (CellSearch, Veridex LLC) was approved by the FDA in these indications. However, to date there is no reliable method to detect CTCs in melanoma (CMC). Studies based on PCR amplification of mRNA by reverse specific melanoma is disappointing. Recently, a new detection system of CMC immunomagnetic was presented (CellSearch, Veridex LLC, United States). This system has the advantage of combining immunomagnetic selection step and a step of identifying by immunofluorescence. A preclinical study on serial dilutions of melanoma cells has shown encouraging results. The investigators propose a prospective study of the CellSearch system in patients with melanoma.
  Primary objective: To determine the effect of treatment on the number of circulating melanoma cells in patients with metastatic melanoma.
  Secondary objectives:
  -  determine the percentage of patients with metastatic melanoma with melanoma cells circulating
  -  seek a relationship between the number of circulating melanoma cells and prognosis in patients with metastatic melanoma
  -  seek a relationship between the change in the number of circulating melanoma cells before / after treatment and tumor response in patients with metastatic melanoma


Eligibility: Inclusion Criteria:
  -  Patients > or = 18 years
  -  Patients with advanced melanoma stage IIIC (unresectable) or stage IV
  -  Patient not treated or not responding to chemotherapy with chemotherapy session last> 1 month
  -  Patients who signed informed consent
  -  Patients presenting no socio-economic, psychological, familial or geographical allow proper understanding of the information leaflet of the protocol or the regular monitoring in the department of dermatology
  -  Patients with a life expectancy greater than 3 months
  -  Patients with melanoma measurable by RECIST version 1.1
  -  Patients with venous good for venipuncture
  Exclusion Criteria:
  -  Patients with contraindication for treatment with chemotherapy or V600E BRAF inhibitor or ipilimumab or have conditions concomitant heavy may interfere with the treatment of metastatic melanoma
  -  Pregnant women or nursing
  -  People vulnerable detainees, adults under guardianship or curatorship, minors.

Relevance to patient case: not relevant
Patient case: 86-year-old female with melanoma; genetic feature: high tumor mutational burden

Clinical trial: A Study Comparing Trametinib and Dabrafenib Combination Therapy to Dabrafenib Monotherapy in Subjects With BRAF-mutant Melanoma

Summary: This is a two-arm, double-blinded, randomized, Phase III study comparing dabrafenib (GSK2118436) and trametinib (GSK1120212) combination therapy to dabrafenib administered with a trametinib placebo (dabrafenib monotherapy). Subjects with histologically confirmed cutaneous melanoma that is either Stage IIIC (unresectable) or Stage IV, and BRAF V600E/K mutation positive will be screened for eligibility. Subjects who have had prior systemic anti-cancer treatment in the advanced or metastatic setting will not be eligible although prior systemic treatment in the adjuvant setting will be allowed. Approximately 340 subjects will be randomized 1:1 (combination therapy: dabrafenib monotherapy). Subjects will be stratified by lactate dehydrogenase (LDH) level (> the upper limit of normal (ULN) versus less than or equal to the ULN) and BRAF mutation (V600E versus V600K). The primary endpoint is investigator-assessed, progression-free survival for subjects receiving the combination therapy compared with those receiving dabrafenib monotherapy. Subjects will be followed for overall survival; crossover will not be permitted.


Eligibility: Inclusion Criteria:
  -  Histologically confirmed cutaneous melanoma that is either Stage IIIC (unresectable) or Stage IV (metastatic), and determined to be BRAF V600E/K mutation-positive using the bioMerieux (bMx) investigational use only (IUO) THxID BRAF Assay (IDE: G120011). The assay will be conducted by a central reference laboratory. Subjects with ocular or mucosal melanoma are not eligible.
  -  The subject must have a radiologically measurable tumor
  -  The subject is able to carry out daily life activities without significant difficulty (ECOG performance status score of 0 or 1).
  -  Able to swallow and retain oral medication
  -  Sexually active subjects must use acceptable methods of contraception during the course of the study
  -  Adequate organ system function and blood counts
  Exclusion Criteria:
  -  Prior treatment with a BRAF or a MEK inhibitor
  -  Prior systemic anti-cancer treatment for Stage IIIC (unresectable) or Stage IV (metastatic) melanoma. Prior systemic treatment in the adjuvant setting is allowed. (Note: Ipilimumab treatment must end at least 8 weeks prior to randomization.)
  -  The subject has received major surgery or certain tyes of cancer therapy with 21 days of starting treatment
  -  Current use of prohibited medication listed in the protocol
  -  Left ventricular ejection fraction less than the lower limit of normal
  -  Uncontrolled blood pressurl
  -  History or current evidence of retinal vein occlusion or central serous retinopathy
  -  Brain metastases unless previously treated with surgery or stereotactic radiosurgery and the disease has been stable for at least 12 weeks
  -  The subject is pregnant or nursing

Relevance to patient case: not relevant
Patient case: 86-year-old female with melanoma; genetic feature: high tumor mutational burden

Clinical trial: Dabrafenib Plus Trametinib vs Vemurafenib Alone in Unresectable or Metastatic BRAF V600E/K Cutaneous Melanoma

Summary: This is a two-arm, open-label, randomised, Phase III study comparing dabrafenib (GSK2118436) and trametinib (GSK1120212) combination therapy to vemurafenib. Subjects with histologically confirmed cutaneous melanoma that is either stage IIIc (unresectable) or stage IV, and BRAF V600E/K mutation positive will be screened for eligibility. Subjects who have had prior systemic anti-cancer treatment in the advanced or metastatic setting will not be eligible although prior systemic treatment in the adjuvant setting will be allowed. Approximately 694 subjects will be randomised 1:1 (combination therapy:vemurafenib). The primary endpoint is overall survival (OS) for subjects receiving the combination therapy compared with those receiving vemurafenib.


Eligibility: Inclusion Criteria:
  -  >= 18 years of age
  -  Stage IIIc or Stage IV BRAF V600E/K cutaneous melanoma
  -  Measurable disease according to RECIST 1.1
  -  Women of childbearing potential with negative serum pregnancy test prior to randomisation
  -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  -  Adequate baseline organ function
  Exclusion Criteria:
  -  Any prior use of a BRAF or MEK inhibitor
  -  Prior systemic anti-cancer treatment in the advanced or metastatic setting; prior systemic treatment in the adjuvant setting is allowed
  -  History of another malignancy (except subjects who have been disease free for 3 years or with a history of completely resected non-melanoma skin cancer)
  -  Known HIV, HBV, HCV infection (except chronic or cleared HBV and HCV infection which will be allowed)
  -  Brain metastases (except if all known lesions were previously treated with surgery or stereotactic radiosurgery and lesions, if still present, are confirmed stable for >= 12 weeks prior to randomisation or if no longer present are confirmed no evidence of disease for >= 12 weeks, and are asymptomatic with no corticosteroid requirements for >= 4 weeks prior to randomisation, and no enzyme inducing anticonvulsants for >= 4 weeks prior to randomisation
  -  History or evidence of cardiovascular risk (LVEF < LLN; QTcB >= 480 msec; blood pressure or systolic >=140 mmHg or diastolic >= 90 mmHg which cannot be controlled by anti-hypertensive therapy)
  -  History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR)

Relevance to patient case: not relevant
Patient case: 86-year-old female with melanoma; genetic feature: high tumor mutational burden

Clinical trial: Radical Fimbriectomy for Young BRCA Mutation Carriers

Summary: Some BRCA-mutated women are reluctant to undergo laparoscopic bilateral salpingo-oophorectomy. The goal of the bilateral laparoscopic radical fimbriectomy the investigators suggest, is to suppress the tubal source of possible dysplastic cells from which can stem this high grade tumor, while preserving a natural ovarian hormonal secretion.

Detailed description: Most of ovarian carcinomas related to BRCA 1 or 2 mutations are of fallopian tube origin and especially from its distant part called the fimbria. These tubal, ovarian or primary peritoneal carcinomas are quite always of high grade serous type. They cannot be effectively screened due to the quickness of their evolution. In this context, a laparoscopic bilateral salpingo-oophorectomy (BSO) is the recommended prophylactic procedure.
  Some BRCA-mutated women are reluctant to undergo this procedure considering the numerous adverse effects on body and quality of life, especially when hormonal replacement is forbidden. This refusal makes them at risk of developing a serous pelvic carcinoma.
  The goal of the bilateral laparoscopic radical fimbriectomy the investigators suggest, is to suppress the tubal source of possible dysplastic cells from which can stem this high grade tumor, while preserving a natural ovarian hormonal secretion

Eligibility: Inclusion Criteria:
  -  Woman aged over 35 years
  -  When project of childbearing is fulfilled
  -  With a BRCA 1 or 2 mutation, or a family history of breast/ovarian cancer
  -  Unprepared to undergo bilateral annexectomy
  -  With or without breast cancer
  -  Patient affiliated to health insurance
  -  Dated and signed informed consent
  Exclusion Criteria:
  -  Menopausal woman defined as :
  Bilateral oophorectomy without hysterectomy and amenorrhea more than 12 months and/or FSH> 20 UI/l History of hysterectomy and FSH> 20 UI/l
  -  Pregnant or breastfeeding woman

Relevance to patient case: not relevant
Patient case: 86-year-old female with melanoma; genetic feature: high tumor mutational burden

Clinical trial: COPARIME: Pilot Study of a Target Detection of Malignant Melanoma

Summary: Melanoma is nowadays an important public health problem because its growing incidence. Mass screening for melanoma is not recommended worldwide because of its low cost-effectiveness. Nevertheless targeted screening for patients at high risk for melanoma is promoted. This study is designed to assess the effectiveness and the acceptability of a melanoma targeted screening of melanoma, to estimate the risk function to develop a melanoma among patients at high risk according to the SAMScore and to estimate the ratio cost/ efficacy of the melanoma targeted screening. A cohort of 7700 patients is carried out in 2 departments covered by a registry of cancers. The recruitment had began in April 2011. Patients assessed at high risk according to the SAMScore were proposed a skin examination by their GP every year.


Eligibility: Inclusion Criteria:
  -  patients more than 18 years old,
  -  consulting their GP,
  -  assessed at risk for melanoma according to the SAMScore
  -  signed the consent.

Relevance to patient case: not relevant
Patient case: 86-year-old female with melanoma; genetic feature: high tumor mutational burden

Clinical trial: Phase 2 Study of Ipilimumab Plus Dacarbazine in Japanese Patients With Advanced Melanoma

Summary: The purpose of this study is to determine the survival rate after 1 year of treatment with ipilimumab plus dacarbazine in patients with previously untreated Stage III (unresectable) or Stage IV melanoma.


Eligibility: Key inclusion criteria:
  -  Japanese patients with histologic diagnosis of malignant melanoma
  -  Previously untreated Stage III with N3 (unresectable) or Stage IV melanoma
  -  Prior adjuvant melanoma therapy permitted
  -  Eastern Cooperative Oncology Group performance status of 0 or 1
  -  Life expectancy of at least 16 weeks in this study
  -  Adequate bone marrow and renal and hepatic function, specifically:
  -  white blood cell count ≥2500/uL, absolute neutrophil count ≥1000/uL, platelet count ≥75,000/uL, hemoglobin level ≥9.0 g/dL, creatinine level ≤2.5*upper limit of normal (ULN), aspartate transaminase/alanine transaminase level <2.5*ULN for patients without liver metastasis and <5*ULN for patients with liver metastasis, total bilirubin level <1.5*ULN (for those with Gilbert's Syndrome, lower than 3.0 mg/dL)
  Key exclusion criteria:
  -  Evidence of brain metastases on brain imaging
  -  Active brain metastases with symptoms or requiring corticosteroid treatment; patients with any other malignancy from which they have been disease-free for fewer than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix
  -  Primary ocular or mucosal melanoma
  -  History of or current active autoimmune disease
  -  History or concurrent disease of gastrointestinal perforations
  -  HIV infection; active Hepatitis B or C or human T-lymphotropic virus type1 infection, based on testing performed during the screening period of this study
  -  Prior or concomitant therapy with any anticancer agent for melanoma, or other investigational anticancer therapies
  -  Prior adjuvant therapy <4 weeks prior to the start of study drug administration
  -  Concomitant therapy with immunosuppressive agents, surgery, or radiotherapy
  -  Prior treatment with CTLA-4 inhibitors/agonists or other experimental immunotherapy drugs
  -  Treatment with other investigational products within 4 weeks prior to initial treatment of study drug

Relevance to patient case: not relevant
Patient case: 86-year-old female with melanoma; genetic feature: high tumor mutational burden

Clinical trial: Natural Dendritic Cell Vaccines in Metastatic Melanoma Patients

Summary: Dendritic cells (DCs) are the professional antigen-presenting cells of the immune system. As such they are currently used in clinical vaccination protocols in cancer patients, and both immunological and clinical responses have been observed. Several subsets of dendritic cells have been characterized in the peripheral blood. One such subset is referred to as plasmacytoid dendritic cells (PDC), another as myeloid dendritic cells (myDC). To date PDC and myDC have not been evaluated for their capability to induce anti-tumor immune responses in patients. For this reason the investigators will perform a safety and efficacy study with PDC and myDC in stage IV melanoma patients.


Eligibility: Inclusion Criteria:
  -  Stage IV melanoma according to the 2001 AJCC criteria. Limited tumor burden; LDH < 2x upper limit of normal
  -  Histological proof of cutaneous melanoma
  -  Melanoma expressing tyrosinase and/or gp100 (approximately 20% of cells or more determined by immunohistochemistry staining)
  -  HLA Type A2
  -  WBC > 3.0 * 10E9/l, lymphocytes > 0.8 * 10E9/l, platelets > 100 * 10E9/l, serum creatinine < 150 umol/l, serum bilirubin < 25 umol/l, normal liver function
  -  Expected adequacy of follow up
  -  Written informed consent
  Exclusion Criteria:
  -  autoimmune disorders, concomitant use of immunosuppressive drugs
  -  serious concomitant disease, serious active infections, other malignancy in the past 5 years with the exception of curatively treated carcinoma in-situ of the cervix/squamous cell carcinoma of the skin
  -  known allergy to shell fish (vaccine contains KLH)
  -  pregnancy or lactation
  -  clinical signs of CNS metastases, in patients with a clinical suspicion of CNS metastases, a CT scan of the brain should be performed to exclude this
  -  prior chemotherapy, immunotherapy, or radiotherapy within three months before planned vaccination is allowed

Relevance to patient case: not relevant
Patient case: 86-year-old female with melanoma; genetic feature: high tumor mutational burden

Clinical trial: C11-Erlotinib PET/CT as a Tool for Identification and Characterization of Tumor With High Expression of Epidermal Growth Factor Receptor(EGFR).

Summary: The EGFR is one of the most frequently overexpressed proteins in various cancers including lung cancer, and is related to tumor progression and resistance to most treatments.
  New treatment strategies targeting EGFR have been developed: "although much work remains to be done, erlotinib has already established itself as part of the therapeutic armamentarium against cancer"(A review of erlotinib and its clinical use. Tang PA, Tsao MS, Moore MJ. Expert Opin Pharmacotherapy. 2006 Feb;7(2):177-93.)
  Noninvasive PET/CT imaging of EGFR expression activity and mutation status in NSCLC could aid in the selection of patients for individualized therapy with EGFR kinase inhibitors.
  Whole-body noninvasive PET/CT imaging could estimate treatment-responsive vs. -resistant tumor burden before the initiation of therapy with EGFR inhibitors.
  The purposes of the study are:
  1. To adjust an optimal treatment for patients with tumors that have high expression of EGFR by identification of this type of cancer using C11-Erlotinib PET/CT during pretreatment work-up; as well as to follow up after treatment response.
  2. To recognize patients with advanced pancreatic cancer responding to treatment with erlotinib and to distinguish them from non-responders.


Eligibility: Inclusion Criteria:
  -  patients with NSC type of lung cancer with high expression of EGFR who are candidates for erlotinib as second / third line of treatment;
  -  patients with advanced pancreatic tumor who are candidates for complex gemcitabine and erlotinib treatment.
  Exclusion Criteria:
  -  lack of histological diagnosis;
  -  not a candidate for erlotinib;
  -  pregnancy.

Relevance to patient case: not relevant
Patient case: 86-year-old female with melanoma; genetic feature: high tumor mutational burden

Clinical trial: Study of Nivolumab (BMS-936558) Compared With Dacarbazine in Untreated, Unresectable, or Metastatic Melanoma

Summary: The purpose of this study is to compare the clinical benefit, as measured by overall survival, of nivolumab with that of. dacarbazine in patients with previously untreated, unresectable, or metastatic melanoma


Eligibility: For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com
  Inclusion Criteria:
  -  Men and women ≥18 years of age
  -  Eastern Cooperative Oncology Group Performance Status of 0 or 1
  -  Untreated and histologically confirmed unresectable Stage III or Stage IV melanoma, as per the staging system of the American Joint Committee on Cancer
  -  Measurable disease as per Response Evaluation Criteria in Solid Tumors 1.1
  -  Tumor tissue from an unresectable or metastatic site of disease must be provided for biomarker analyses
  -  Known BRAF wild-type, as per regionally acceptable V600 mutational status testing. BRAF mutant patients and those with indeterminate or unknown BRAF status are not permitted to randomize
  Exclusion Criteria:
  -  Active brain metastases or leptomeningeal metastases
  -  Ocular melanoma
  -  Any active, known, or suspected autoimmune disease

Relevance to patient case: not relevant