araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 48-year-old female with melanoma; genetic feature: tumor cells with >50% membranous PD-L1 expression

Clinical trial: Efficacy Study of Pharmacokinetic(PK)/Pharmacodynamic(PD) Relationship of Monotherapy MORAb-004 in Metastatic Melanoma

Summary: This is a global, Phase 2, open label, dose selection, proof-of-concept study to assess progression free survival in subjects with metastatic melanoma.
  80+ subjects at 29 sites in the U.S., U.K., Germany and Australia will be randomized into one of two dose groups: 2 mg/kg, 4 mg/kg. Weekly treatment will continue until disease progression.
  Subjects must have measurable disease by CT Scan or MRI and must have completed at least one prior round of chemotherapy.
  Subjects will be assessed for Efficacy, PK/PD, Overall survival, and Safety (Adverse Events/Adverse Events of Interest, Electrocardiograms (ECG's), clinical labs, physical exams/vital signs, tolerability).

Detailed description: MORAb-004 is a monoclonal antibody directed against endosialin, a cell surface glycoprotein, which is expressed on cells involved in tumor vasculature. Studies have found endosialin to play a key role in tumor growth and neovessel formation in numerous cancer types including melanoma. Preclinical pharmacological studies have shown that MORAb-004 is a potentially useful anti-cancer agent. This clinical trial is being performed to determine the efficacy of MORAb-004 at two dose levels in subjects with metastatic melanoma, as well as to establish serum pharmacokinetics and pharmacodynamics of the antibody.

Eligibility: Inclusion Criteria:
  -  Histologically confirmed diagnosis of metastatic melanoma
  -  At least one prior line of systemic treatment with confirmed progression of disease
  -  Measurable disease, as defined by RECIST, assessed within 4 wks prior to study entry
  -  At least 3 week interval between first infusion of test article and most recent prior systemic anticancer therapy
  -  ECOG Performance Status of 0 or 1
  Exclusion Criteria:
  -  Evidence of other active malignancy requiring treatment within the last 5 years (other than basal cell or squamous cell carcinoma of the skin), or active brain metastasis
  -  Clinically significant heart disease (Congestive heart failure of NYHA Class 3 or 4, angina not well controlled by medication, or myocardial infarction within 6 mos.), or ECGs demonstrating clinically significant arrhythmias
  -  Brain metastasis
  -  Known allergic reaction to a prior monoclonal antibody therapy
  -  Previous treatment with MORAb-004

Relevance to patient case: not relevant
Patient case: 48-year-old female with melanoma; genetic feature: tumor cells with >50% membranous PD-L1 expression

Clinical trial: A Phase 1 Study of Atezolizumab (an Engineered Anti-Programmed Death-Ligand 1 [PDL1] Antibody) to Evaluate Safety, Tolerability and Pharmacokinetics in Participants With Locally Advanced or Metastatic Solid Tumors

Summary: This Phase I, multicenter, first in human, open-label, dose escalation study will evaluate the safety, tolerability, and pharmacokinetics of atezolizumab (MPDL3280A) administered as single agent by intravenous (IV) infusion every three weeks (q3w) to participants with locally advanced or metastatic solid malignancies or hematologic malignancies. The study will be conducted in two cohorts: Dose-escalation cohort and Expansion cohort.


Eligibility: Inclusion Criteria:
  -  Age greater than equal to [>/=] 18 years, participants who are 16 to 17 years old would be enrolled after consultation with the Medical Monitor
  -  Histologically or cytologically documented, incurable or metastatic solid tumor or hematologic malignancy that is advanced (non-resectable) or recurrent and progressing since the last anti-tumor therapy and for which no recognized standard curative therapy exists
  -  Representative tumor specimens in paraffin blocks (preferred) or at least 15 unstained slides, with an associated pathology report
  -  Adequate hematologic and end organ function
  -  Measurable disease per RECIST v1.1 for participants with solid malignancies. Disease-specific criteria for participants with prostate cancer, glioblastoma multiforme (GBM), malignant lymphoma, or multiple myeloma
  -  For women of childbearing potential: agreement to remain abstinent or use contraceptive methods
  -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  -  For participants who will undergo serial biopsy dose-escalation cohort, baseline tumor tissue samples should be of core needle biopsies for deep tumor tissue or organs or excisional or punch biopsies for cutaneous or subcutaneous lesions (>/=5 millimeter [mm] in diameter amenable to serial biopsy)
  Exclusion Criteria:
  -  Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases
  -  Known hypersensitivity to pharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
  -  History or risk of autoimmune disease (for example, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis)
  -  History of human immunodeficiency virus (HIV) infection, active hepatitis B (chronic or acute), or hepatitis C infection
  -  Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1
  -  Malignancies other than disease under study within 5 years prior to Cycle 1, Day 1
  -  Participants with prior allogeneic bone marrow transplantation or prior solid organ transplantation

Relevance to patient case: not relevant
Patient case: 48-year-old female with melanoma; genetic feature: tumor cells with >50% membranous PD-L1 expression

Clinical trial: Randomized Study of Hypofractionated and Conventional Fractionation Radiotherapy After Breast Conservative Surgery

Summary: Early-stage breast cancer patients treated with breast conservative surgery are enrolled in this study if they meet defined criteria. Patients are randomized into two groups: conventional fractionation radiotherapy and hypofractionated radiotherapy.The hypothesis is that conventional fractionation radiotherapy and hypofractionated radiotherapy have similar efficacy and toxicity.


Eligibility: Inclusion Criteria:
  1. KPS>=60
  2. histology confirmed invasive breast cancer
  3. received breast conservative surgery(wide local excision and axilla dissection, or axillary sentinel node biopsy if sentinel node is negative)
  4. surgical margins negative
  5. primary tumor ≤5cm in the largest diameter
  6. no internal mammary node or supraclavicular node metastases or distant metastasis
  7. can tolerate chemotherapy,hormone therapy (if needed) and radiotherapy
  8. for patients not need chemotherapy，enrollment date is required no more than 8 weeks from surgery date
  9. for patients with chemotherapy first,enrollment date is required no more than 8 weeks from the last date of chemotherapy
  10. patients signed written inform consent form
  Exclusion Criteria:
  1. ductal carcinoma in situ
  2. prior neoadjuvant chemotherapy
  3. prior breast cancer history
  4. bilateral breast cancer
  5. pregnant or during lactation
  6. prior or concomitant malignant tumor excluded skin cancer(not malignant melanoma) and cervix carcinoma in situ
  7. active collagen vascular disease
  8. prior neoadjuvant hormone therapy
  9. immediate ipsilateral breast reconstruction

Relevance to patient case: not relevant
Patient case: 48-year-old female with melanoma; genetic feature: tumor cells with >50% membranous PD-L1 expression

Clinical trial: A Phase I Study of Oral LGX818 in Adult Patients With Advanced or Metastatic BRAF Mutant Melanoma

Summary: CLGX818X2101 is a first-time in-human, phase I study to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of daily administered LGX818 (daily, twice daily and/or every-other-day), a RAF kinase inhibitor. Patients with locally advanced or metastatic melanoma harboring the BRAF V600 mutation (during dose escalation phase and expansion phase) and patients with metastatic colorectal cancer harboring the BRAF V600 mutation (during the expansion phase) will be enrolled. The study consists of a dose escalation part were cohorts of patients will receive escalating oral doses of LGX818, followed by a safety dose expansion part were patients will be treated with oral dose of LGX818 given at the MTD or RP2D.


Eligibility: Inclusion Criteria:
  For the dose escalation phase:
  1. Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage IIIB to IV per American Joint Committee on Cancer [AJCC]). For the dose expansion phase: (i) Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage IIIB to IV per American Joint Committee on Cancer [AJCC]), or (ii) confirmed diagnosis and non-resectable advanced metastatic colorectal cancer (mCRC) for which no further effective standard therapy exists.
  2. Written documentation of BRAF V600E mutation, or any other BRAF V600 mutation.
  3. Evidence of measurable disease
  Exclusion Criteria:
  1. Previous therapy with a MEK inhibitor.
  2. Symptomatic or untreated leptomeningeal disease.
  3. Symptomatic or untreated brain metastasis.Patients previously treated for these conditions that are asymptomatic in the absence of corticosteroid therapy are allowed to enroll. Brain metastasis must be stable with verification by imaging.
  4. Known acute or chronic pancreatitis.
  5. Clinically significant cardiac disease
  6. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LGX818
  7. Previous or concurrent malignancy. Exceptions to this exclusion criteria include: adequately treated basal cell or squamous cell skin cancer; in situ carcinoma of the cervix, treated curatively and without evidence of recurrence for at least 3 years prior to study entry; or other solid tumor treated curatively, and without evidence of recurrence for at least 3 years prior to study entry.
  8. 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 hCG laboratory test (> 5 mIU/mL).
  9. History of thromboembolic or cerebrovascular events within the last 6 months
  Other protocol-defined inclusion/exclusion criteria may apply

Relevance to patient case: not relevant
Patient case: 48-year-old female with melanoma; genetic feature: tumor cells with >50% membranous PD-L1 expression

Clinical trial: Phase 1 Biomarker Study of Anti-PDL-1 in Advanced Melanoma

Summary: The purpose of this study is to evaluate pharmacodynamic changes of BMS-936559 treatment on the biomarkers measured in the peripheral blood and tumor tissues of subjects with unresectable Stage III or IV Melanoma.


Eligibility: Inclusion Criteria:
  -  Men and women ≥ 18 years
  -  Eastern Cooperative Oncology Group (ECOG) status = 0 to 1
  -  Subjects with unresectable Stage III or IV Melanoma who are either refractory or intolerant to, or have refused standard therapy for treatment of metastatic Melanoma
  -  Subject must have histologic or cytologic confirmation of advanced Melanoma
  -  Subjects must have at least one measurable lesion at baseline by computed tomography (CT) or magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
  -  Subjects must have at least 1 tumor site that can be biopsied at acceptable clinical risk and must consent to pre- and post-treatment biopsies
  Exclusion Criteria:
  -  Active or progressing brain metastases
  -  Other concomitant malignancies (with some exceptions per protocol)
  -  Active or history of autoimmune disease
  -  Positive test for human immunodeficiency virus (HIV) 1&2 or known acquired immunodeficiency syndrome (AIDS)
  -  History of any hepatitis
  -  Prior therapy with any antibody/drug that targets the T cell coregulatory proteins, including but not limited to, anti Programmed cell death 1 (PD-1), anti Programmed cell death ligand 1 (anti-PD-L1), anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40 or anti Cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) antibodies

Relevance to patient case: possibly relevant
Patient case: 48-year-old female with melanoma; genetic feature: tumor cells with >50% membranous PD-L1 expression

Clinical trial: Phase I/IIa AdCD40L Immunogene Therapy for Malignant Melanoma and Other Solid Tumors

Summary: In this phase I/II trial, immunostimulatory gene therapy (AdCD40L) will be investigated. In Part 1 patients with melanoma will receive AdCD40L as mono therapy. In Part 2A, patients with melanoma and patients with other solid tumors will receive AdCD40L in combination with low dose cyclophosphamide. In Part 2B, patients with melanoma will receive AdCD40L in combination with one local radiotherapy and cyclophosphamide.

Detailed description: In this phase I/II trial, immunostimulatory gene therapy (AdCD40L) will be investigated. In Part 1 patients with melanoma (n=6) will receive AdCD40L as mono therapy. In Part 2A, patients with melanoma (n=9) and patients with other solid tumors (n=6) will receive AdCD40L in combination with low dose cyclophosphamide. In Part 2B, patients with melanoma will receive AdCD40L in combination with one local radiotherapy and cyclophosphamide. AdCD40L is given by weekly injections of 2.5x10e11 VP, 4x; total dose 1x10e12 VP. A maximum of 30 patients will be included in this trial.
  AdCD40L is an adenoviral nonreplicating vector carrying the human CD40L gene. AdCD40L infects tumor cells upon intratumoral injection and deliver the CD40L gene into the cells whereupon the virus is destroyed. CD40L is then expressed as a membrane-bound protein and interacts with the CD40 receptor expressed by for example dendritic cells (DCs) in the tumor area. DCs mature upon CD40/CD40L interactions and activates tumor-specific T cell responses.

Eligibility: Inclusion Criteria:
  -  Histologically proven diagnosis of malignant solid cancer, ECOG 0-2.
  -  Disease progression on established treatments or patients not eligible to standard options.
  -  Signed informed consent must be obtained.
  Exclusion Criteria:
  -  Pregnancy.
  -  Life expectancy less than 3 months.
  -  Any significant medical or psychiatric illness that would prevent the patient from giving informed consent or from following the study procedures.
  -  Patients with severe systemic autoimmune disease.
  -  Patients that do not consent to that tissue and blood samples are stored in a biobank.

Relevance to patient case: not relevant
Patient case: 48-year-old female with melanoma; genetic feature: tumor cells with >50% membranous PD-L1 expression

Clinical trial: Comparative Microarray Analysis in Primary Cutaneous Malignant Melanoma

Summary: Perturbations in microRNA (miRNA) expression profiles has been reported for cutaneous malignant melanoma (CMM). This study will be an exploratory analysis by miRNA expression profiling using microarrays.

Detailed description: Perturbations in microRNA (miRNA) expression profiles has been reported for cutaneous malignant melanoma (CMM). With regards to a rapidly growing number of newly discovered miRNA sequences, the availability of up-to-date miRNA expression profiles for primary cutaneous malignant melanoma (PCMM), cutaneous malignant melanoma metastases (CMMM) and benign melanocytic naevi (BMN) is limited. Patients with PCMM, CMMM and BMN are included in the study to perform an exploratory analysis by miRNA expression profiling using microarrays. Expression levels of miRNA candidates will be validated by TaqMan real-time quantitative polymerase chain reaction (RT-PCR).

Eligibility: Inclusion Criteria:
  -  Primary Cutaneous Malignant Melanoma
  -  Cutaneous Malignant Melanoma Metastases
  -  Benign Melanocytic Naevi
  Exclusion Criteria:
  - Other Skin Cancer than Primary Cutaneous Malignant Melanoma

Relevance to patient case: not relevant
Patient case: 48-year-old female with melanoma; genetic feature: tumor cells with >50% membranous PD-L1 expression

Clinical trial: cKIT, BRAF/NRAS Mutations in Advanced Melanoma : Clinical Outcome in Response to Tyrosine-kinase Inhibitors - KitMel Project

Summary: Background: Metastatic melanoma has a devastating prognosis and is one of the top causes of cancer death in young patients. Until now, available therapies were few and unreliable, but recent understanding of melanomas' molecular pathways has improve their classification and new clinical strategies have been proposed.
  Initial studies showed that B-Raf/N-Ras mutations (respectively V600E and Q61) are the most frequent alteration being present in 70 to 80% of melanomas, characterizing non Chronic Sun-induced Damage skins (CSD). These include Superficial Spreading Melanomas (SSM) and Nodular Melanomas (NM). Other studies showed that c-Kit mutations are presently the predominant activating mutation (20 - 40 %) in Acro-Lentiginous Melanomas (ALM), Mucous Melanomas (MM) and in melanomas arising on CSD skin. c-Kit mutation pattern is more complex with four exons being affected leading to different mutations, which incidence and biological impact are less documented.
  BRAF/NRAS genetics alterations drive constantly cell growth, being thus attractive targets. Spectacular results have indeed been obtained with the BRAF inhibitor that targets the V600E BRAF-mutated form. Data from GIST disease revealed that the different c-Kit mutations modulate differently c-Kit function and the response to targeted therapies.
  Because c-Kit targeted therapy is a critical clinical issue, the investigators aimed to identify the most frequent mutations present in our population to propose appropriate screening test and adapt the therapy.
  Methods: 250 melanoma samples corresponding to an homogeneous white-Caucasian population (Brittany, France) will be screened. c-Kit exons 11, 13, 17 and 18 will be sequenced (direct sequencing and pyrosequencing when possible). c-Kit copy number will be quantified by q-PCR and level of c-Kit determined by immunohistochemistry (IHC, CD117). Samples will also be analyzed for B-Raf mutations in codon 464, 466, 469 and 600, and for N-Ras mutations in codon 12, 13 and 61 (Pyrosequencing).
  Expected Results:
  Taken together, the investigators anticipate that the present genetic analysis of the tumours from patients with advanced melanoma will first document the type and frequency of cKit mutations, will confirm or not that BRAF, NRAS and cKit mutations are mutually exclusive and document their repartition in the melanomas sub-types. Finally this study will clue researchers in to how well patients will respond to a therapy that targets the growth-promoting proteins BRAF/NRAS and cKIT.


Eligibility: Inclusion Criteria:
  -  melanoma
  -  white caucasian population

Relevance to patient case: not relevant
Patient case: 48-year-old female with melanoma; genetic feature: tumor cells with >50% membranous PD-L1 expression

Clinical trial: Circulating Tumor Cells and Melanoma: Comparing the EPISPOT and CellSearch Techniques

Summary: The main objective of this study is to compare results for the detection of circulating melanoma cells (CMC) using CellSearch versus EPISPOT (EPithelial ImmunoSPOT) techniques between a group of patients with metastatic melanoma and a group of hospitalized control patients.

Detailed description: The secondary objectives of this study include:
  A. To compare the following elements between the two patient groups:
  -  the number of CMCs per ml of blood as determined by EPISPOT
  -  the number of CMCs per ml of blood as determined by CellSearch
  -  the percentage of patients with at least 2 CMCs per ml of blood according to the two techniques
  -  the % of CMCs expressing KI67
  -  the % of CMCs expressions S100 (only the EPISPOT technique)
  B. To compare the EPISPOT and CellSearch techniques is terms of the following:
  -  the number of CMCs detected per ml blood
  -  the number of CMCs expressing antigen KI67
  C. To re-evaluate the 2-CMC per ml blood threshold

Eligibility: Inclusion Criteria:
  -  The patient must have given his/her informed and signed consent
  -  The patient must be insured or beneficiary of a health insurance plan
  -  The patient is available, within the hours of his/her normally scheduled medical care, for blood sampling at 8 am and 4 pm on the same day.
  Inclusion Criteria for patients:
  -  Stage 4 melanoma, without other associated neoplasms
  Inclusion Criteria for controls:
  -  Patient without cancer, nor history of cancer
  Exclusion Criteria:
  -  The patient is participating in another study
  -  The patient is in an exclusion period determined by a previous study
  -  The patient is under judicial protection, under tutorship or curatorship
  -  The patient refuses to sign the consent
  -  It is impossible to correctly inform the patient
  -  The patient is pregnant, parturient, or breastfeeding
  -  The patient has a contra-indication for a treatment used in this study
  Exclusion criteria for patients:
  -  Stage 1 to 3 melanoma, or other types of cancer
  Exclusion criteria for controls:
  -  History of cancer

Relevance to patient case: not relevant
Patient case: 48-year-old female with melanoma; genetic feature: tumor cells with >50% membranous PD-L1 expression

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