araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

Clinical trial: Detection of KRAS, NRAS et BRAF Mutations in Plasma Circulating DNA From Patients With Metastatic Colorectal Cancer

Summary: RAS genotyping is mandatory for the prescription of anti-EGFR (epidermal growth factor receptor) therapies in patients with metastatic colorectal cancer. The standard genotyping is assessed on formalin-fixed paraffin embedded tumour tissue. This study compares RAS and BRAF genotyping results achieved in analyzing circulating plasma DNA using OncoBEAM™ technique with those achieved using the standard genotyping techniques and formalin-fixed paraffin embedded samples.

Detailed description: The study will be proposed to all patients with a metastatic colorectal cancer.
  Study information will be given to the patient during a routine medical examination. The patient will be included after checking inclusion criteria and signature of the informed consent form
  Blood sampling (30 ml) will be performed before the initiation of the first line metastatic chemotherapy.

Eligibility: Inclusion Criteria:
  -  Adult subjects with newly diagnosed, anti EGFR treatment naïve metastatic colorectal cancer
  -  Standard of Care RAS/RAF tests performed on FFPE tumor sample as part of routine
  -  Patient information and written informed consent form signed
  -  Patient must be affiliated to a social security system
  -  Age : 18 years and older
  Exclusion Criteria:
  -  Patient bearing non-metastatic colorectal cancer
  -  Patient with local relapse only
  -  Patient with exclusive nodal metastases
  -  Patient whose health contraindicates a 30 ml blood sample
  -  Blood transfusion within 1 week prior blood collection
  -  Patient having received any chemotherapy or / and radiotherapy within 15 days prior to blood collection
  -  History of another primary cancer within the last 5 years, with the exception of non-melanomatous skin cancer and carcinoma in situ of the cervix
  -  Persons deprived of liberty or under supervision

Relevance to patient case: not relevant
Patient case: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

Clinical trial: A Study to Detect V-Raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF) V600 Mutation on Cell-Free Deoxyribonucleic Acid (cfDNA) From Plasma in Participants With Advanced Melanoma

Summary: This is a single arm, multicenter, open label, and non-randomized clinical study on adult participants with unresectable or metastatic melanoma. The study will be conducted in two phases. Pre-screening phase will assess the BRAF V600 mutation in a new mutation analysis triggered by a mutant plasma cfDNA test result. Treatment phase will assess the clinical outcome for the participants treated with vemurafenib plus cobimetinib. The length of the study will be approximately 38 months.


Eligibility: Inclusion Criteria:
  Pre-screening phase:
  -  Participants with histologically confirmed cutaneous melanoma, either unresectable Stage IIIc or Stage IV metastatic melanoma, as defined by American Joint Committee on Cancer 7th edition
  -  Documentation of BRAF V600 test result mutation-positive status on melanoma tumor tissue using a validated tissue test
  Treatment Phase:
  -  Eastern Cooperative Oncology Group performance status of 0-2
  -  Adequate hematologic and end organ function obtained within 14 days prior to first dose of study drug treatment
  -  Negative serum pregnancy test prior to commencement of dosing in women of childbearing potential
  -  Absence of any psychological, familial, sociological, or geographical condition that potentially hampers compliance with the study protocol and treatment regimen and follow-up after treatment discontinuation schedule
  -  Female participants of childbearing potential and male participants with partners of childbearing potential must agree to always use two effective forms of contraception during the course of this study and for at least 6 months after completion of study therapy
  -  Participants should be able to swallow tablets
  -  Documentation of BRAF mutation positive status in melanoma tissue
  Exclusion Criteria:
  Treatment Phase:
  -  History of prior rapidly accelerated fibrosarcoma or mitogen-activated protein kinase pathway inhibitor treatment
  -  Use of prior chemotherapy or immunotherapy (including treatment with an anti-programmed death 1, or anti- programmed death ligand 1 or anti-cytotoxic T-lymphocyte-associated protein 4 monoclonal antibody) within 4 weeks before first study drug administration
  -  Palliative radiotherapy within 14 days prior to the first dose of study treatment
  -  Evidence of retinal pathology on ophthalmologic examination
  -  Systemic risk factors for retinal vein occlusion
  -  History of clinically significant cardiac dysfunction
  -  Current severe, uncontrolled systemic disease
  -  Pregnancy, lactating or breast feeding
  -  Intake of St. John's wort or hyperforin (a potent cytochrome P450 3A4 [CYP3A4 enzyme inducer] and grapefruit juice (a potent CYP3A4 enzyme inhibitor) at least 7 days prior to initiation of and during the study treatment

Relevance to patient case: possibly relevant
Patient case: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

Clinical trial: Clinical and Histological Features of Head and Neck Melanoma

Summary: The worldwide incidence of cutaneous melanoma has been increasing for the last 30 years in western populations. Among all melanomas, those located on the head and neck are more frequent than expected regarding the surface of this anatomical area, occur in older subjects than melanomas at other sites and have a worse prognosis than melanomas at other sites. The question whether head and neck melanomas could be a distinct entity has been debated.

Detailed description: Aim of the study was to compare clinical and histological characteristics between head and neck melanomas and melanomas at other sites.

Eligibility: Inclusion Criteria:
  -  patients with melanoma
  -  melanoma diagnosed between January 2004 and December 2011
  -  patients living in Champagne-Ardenne

Relevance to patient case: not relevant
Patient case: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

Clinical trial: A Study of the Anti-PD1 Antibody PDR001, in Combination With Dabrafenib and Trametinib in Advanced Melanoma

Summary: To evaluate the safety and efficacy of the combination of an anti-PD-1 antibody (Spartalizumab (PDR001)), a BRAF inhibitor (dabrafenib) and a MEK inhibitor (trametinib) in unresectable or metastatic BRAF V600 mutant melanoma


Eligibility: Inclusion criteria Part 1: Safety run-in
  -  Histologically confirmed, unresectable or metastatic melanoma with BRAF V600 mutation
  -  Aspartate transaminase (AST) < 2.5× ULN and Alanine transaminase (ALT) < 2.5× ULN
  -  ECOG performance status ≤ 1
  Part 2: Biomarker cohort
  -  Histologically confirmed, unresectable or metastatic melanoma with BRAF V600 mutation
  -  At least two cutaneous or subcutaneous or nodal lesions for tumor sample collection
  -  ECOG performance status ≤ 2
  Part 3: Double-blind, randomized, placebo-controlled part
  -  Histologically confirmed, unresectable or metastatic melanoma with BRAF V600 mutation
  -  ECOG performance status ≤ 2
  Exclusion Criteria:
  Part 1: Safety run-in
  -  Subjects with uveal or mucosal melanoma
  -  Any history of CNS metastases
  -  Prior systemic anti-cancer treatment for unresectable or metastatic melanoma
  -  Prior loco-regional treatment for unresectable or metastatic melanoma in the last 6 month
  -  Prior neoadjuvant and/or adjuvant therapy for melanoma completed less than 6 months
  -  Radiation therapy within 4 weeks prior to start of study treatment
  -  Active, known, suspected or a documented history of autoimmune disease
  Parts 2 & 3: Biomarker cohort & double-blind, randomized, placebo-controlled part
  -  Subjects with uveal or mucosal melanoma
  -  Clinically active cerebral melanoma metastasis
  -  Prior systemic anti-cancer treatment for unresectable or metastatic melanoma
  -  Prior loco-regional treatment for unresectable or metastatic melanoma in the last 6 month
  -  Prior neoadjuvant and/or adjuvant therapy for melanoma completed less than 6 months
  -  Radiation therapy within 4 weeks prior to start of study treatment
  -  Active, known, suspected or a documented history of autoimmune disease
  Other protocol-defined Inclusion/Exclusion may apply.

Relevance to patient case: possibly relevant
Patient case: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

Clinical trial: A Phase Ib Study of LXH254-centric Combinations in NSCLC or Melanoma

Summary: To characterize safety and tolerability and identify a recommended dose and regimen for the LXH254 in combination with LTT462 or trametinib or ribociclib.


Eligibility: Inclusion Criteria:
  -  Patients must have advanced or metastatic NSCLC or melanoma
  -  Presence of KRAS or BRAF mutation (NSCLC) or NRAS mutation (melanoma) in tumor tissue
  -  All patients participating in this clinical trial must have progressed following standard therapy or, in the opinion of the Investigator, no effective standard therapy exists, is tolerated, appropriate or is considered equivalent to study treatment.
  -  ECOG (Eastern Cooperative Oncology Group) performance status ≤ 2
  Exclusion Criteria:
  -  Dose expansion - KRAS or NRAS mutant patients groups: Prior treatment with a RAFi (including any BRAFi and pan-RAFi), MEKi and/or ERKi. BRAF mutant patients group: Prior treatment with an ERKi and/or a pan-RAFi.
  -  History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
  -  Any medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.
  -  Patients receiving proton pump inhibitors (PPI) which cannot be discontinued 3 days prior to the start study treatment and for the duration of the study.
  -  Patients with Gilbert's syndrome or other heritable diseases of bile processing.
  Other protocol-defined inclusion/exclusion criteria may apply

Relevance to patient case: possibly relevant
Patient case: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

Clinical trial: PROCLAIM-CX-072: A Trial to Find Safe and Active Doses of an Investigational Drug CX-072 for Patients With Solid Tumors or Lymphomas

Summary: The purpose of this first-in-human study of CX-072 is to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of CX-072 administered intravenously (IV) as a single agent or in combination with ipilimumab or vemurafenib in adult subjects with advanced or recurrent solid tumors or lymphomas. PROCLAIM-CX-072: PRObody CLinical Assessment In Man CX-072 clinical trial
  CX-072 is a Probody™ therapeutic directed against PD-L1 (programmed cell death ligand 1). Probody therapeutics are proteolytically-activatable antibodies (Abs) designed to widen the therapeutic index by minimizing drug interaction with normal tissue while retaining anti-tumor activity. Probody therapeutics are "masked" to attenuate binding to target in healthy tissue but can become "unmasked" in the tumor microenvironment by tumor-specific protease activity.
  PROBODY is a trademark of CytomX Therapeutics, Inc.


Eligibility: Inclusion Criteria:
  1. Histologically confirmed diagnosis of metastatic or advanced unresectable tumors that progressed on standard therapy
  2. Agreement to provide mandatory archival tissue or fresh biopsy.
  3. At least 18 years of age.
  Exclusion Criteria:
  1. Prior therapy with a chimeric antigen receptor (CAR) T-cell containing regimen.
  2. History of severe allergic or anaphylactic reactions to human monoclonal antibody therapy or known hypersensitivity to any Probody therapeutic.
  3. Active or history of uveal, mucosal, or ocular melanoma. Human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS)-related illness, chronic hepatitis B or C.
  4. History of or current active autoimmune diseases, including but not limited to inflammatory bowel diseases, rheumatoid arthritis, autoimmune thyroiditis, autoimmune hepatitis, systemic sclerosis, systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies, or type 1 insulin dependent diabetes mellitus.
  5. History of syndrome or medical condition(s) that requires systemic steroids (> 10 mg daily prednisone equivalents) or immunosuppressive medications.
  6. History of allogeneic tissue/solid organ transplant, prior stem cell or bone marrow transplant.
  7. Chemotherapy, biochemotherapy, radiation or immunotherapy or any investigational treatment within 30 days prior to receiving any study drug.
  8. Major surgery (requiring general anesthesia) within 3 months or minor surgery (excluding biopsies conducted with local/topical anesthesia) or gamma knife treatment within 14 days (with adequate healing) of administration of any study drug.

Relevance to patient case: not relevant
Patient case: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

Clinical trial: Tolerance of Targeted Therapy Used in Metastatic Melanoma in Patients Aged Over 65 and 75-year-old

Summary: Since 2013, therapeutic care of metastatic melanoma (MM) has greatly improved, especially thanks to BRAF and MEK targeted therapies. The efficacy of these treatments that are now used daily at first line for BRAF mutated MM is widely approved. Their toxicities, in monotherapy or in association, are also well-known: fever, arthralgias, digestive disorders, cutaneous rash, fatigue, photosensitivity, alopecia, cutaneous hyperkeratosis, squamous cell carcinomas, keratoacanthomas, de novo melanomas… However, onco-dermatologists are more and more faced with MM of elderly patients. Indeed, life expectancy continues to increase and the over-75-year-old age group is becoming larger. These patients are still active but much more vulnerable. Nevertheless, there is no data in the literature for this fragile population except the MM pivotal studies subgroups of those over 65-year-old. The results vary with different regimens. Therefore, there is a wide lack of information that could help make a therapeutic decision, inform patients, prevent or treat side effects of BRAF and MEK inhibitors in elderly patients

Detailed description: Since 2013, therapeutic care of metastatic melanoma (MM) has greatly improved, especially thanks to BRAF and MEK targeted therapies. The efficacy of these treatments that are now used daily at first line for BRAF mutated MM is widely approved. Their toxicities, in monotherapy or in association, are also well-known: fever, arthralgias, digestive disorders, cutaneous rash, fatigue, photosensitivity, alopecia, cutaneous hyperkeratosis, squamous cell carcinomas, keratoacanthomas, de novo melanomas… However, onco-dermatologists are more and more faced with MM of elderly patients. Indeed, life expectancy continues to increase and the over-75-year-old age group is becoming larger. These patients are still active but much more vulnerable. Nevertheless, there is no data in the literature for this fragile population except the MM pivotal studies subgroups of those over 65-year-old. The results vary with different regimens. Therefore, there is a wide lack of information that could help make a therapeutic decision, inform patients, prevent or treat side effects of BRAF and MEK inhibitors in elderly patients. This work aims to study the targeted therapies tolerance in over 65 or 75-year-old patients with BRAF mutated MM. The French clinical and biological database MELBASE will be analysed to carry out a descriptive retrospective multicentric study. This real-life assessment of the adverse effects in older patients will result in more adapted therapeutic decisions, better informed patients and improved follow-up care in order to increase quality of life and life expectancy.

Eligibility: Inclusion Criteria:
  -  Metastatic melanoma
  Exclusion Criteria:
  -  none

Relevance to patient case: not relevant
Patient case: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

Clinical trial: The Impact of Melanoma and Drug Treatment in the Real World

Summary: An observational, non-interventional registry study to collect real-world data from people living with melanoma and its treatment, which will be available to researchers to further the knowledge of melanoma and improve patient care.

Detailed description: The registry uses Vitaccess' MyRealWorld(tm) digital real-world evidence platform, and has been developed in collaboration with the patient advocacy group Melanoma UK.
  Eligible participants install a study app on their smartphone or tablet. Researchers access aggregated, anonymised data via a cloud-based research portal.
  The platform provides benefits to participants, which it is hoped will encourage persistence with data submission; these include options to upload electronic documents such as scans, and access an online melanoma community.
  The aggregated data are available in close to real time via "dashboards" and can be analysed according to a number of pre-set criteria (e.g. disease stage, age, geographic location).
  State-of-the-art technologies and security policies are used in the platform to ensure industry-standard data storage and privacy for all users. Participants' personally identifiable information will remain confidential at all times, and researchers will not be able to identify individuals.

Eligibility: Inclusion Criteria:
  -  adults with melanoma of any stage, resident in the UK with National Health Service (NHS) or Community Health Index (CHI) number, aged 18 and over, current or previous diagnosis of melanoma, willing to use their own smartphone or tablet.
  Exclusion Criteria:
  -  no specific exclusion criteria

Relevance to patient case: not relevant
Patient case: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

Clinical trial: Therapeutic Drug Monitoring of BRAF-mutated Advanced Melanoma

Summary: BRAF V600-mutant metastatic melanoma are commonly treated using a combination of anti-BRAF and anti-MEK tyrosine kinase inhibitors (TKIs). The OPTIMEL trial aims to study the interest of therapeutic drug monitoring (TDM) of TKIs and circulating tumor DNA (ctDNA) detected in plasma of patients with metastatic melanoma for disease monitoring. 35 patients with metastatic melanoma and treated with dabrafenib and trametinib will be enrolled in this trial. Blood samples will be collected for the determination of TKIs concentration and ctDNA detection.


Eligibility: Inclusion Criteria:
  -  Men and women 18 years of age and older
  -  Histologic proven advanced skin melanoma (Stage IV or stage IIIc inoperable) with BRAF V600 mutation
  -  Patient who will treated with combined kinase inhibitors (dabrafenib + trametinib).
  -  Patient able to stand a blood collection of 20 mL
  -  Ability to provide an informed written consent form
  -  Patient must be affiliated to a social security system
  -  Patient's legal capacity to consent to study participation and to understand and comply with the requirements of the study.
  Exclusion Criteria:
  -  Patient with mucosal melanoma
  -  Patient with non-metastatic skin melanoma (All stages except stage IV and stage III C inoperable)
  -  Patient with another synchronous cancer, or within 3 years
  -  Patient with a contraindication to blood collection of 20 mL
  -  Patient deprived of liberty or under supervision
  -  Patient unable to receive kinase inhibitor therapy
  -  Patient treated with another combined kinase inhibitors than dabrafenib and trametinib
  -  Pregnant or breastfeeding women
  -  Patient (man or woman) of childbearing age who does not agree to use of contraceptive methods validated during the study

Relevance to patient case: not relevant
Patient case: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

Clinical trial: Detection of Plasmatic Cell-free BRAF and NRAS Mutations : a New Tool for Monitoring Patients With Metastatic Malignant Melanoma Treated With Targeted Therapies or Immunotherapy ( MALT )

Summary: The main objective of this project is to perform a longitudinal monitoring of BRAF and NRAS cell-free DNA in a large cohort of metastatic melanomas patients before treatment and during the follow-up. Results will be compared with clinical data as imaging (based on RECIST criteria) and the activity of lactate dehydrogenase in serum (LDH).

Detailed description: During a consultation of follow-up for an advanced malignant melanoma (stage IIIb or IIIC or IV), an investigator presents the study to the patient and give him the note of information and the informed consent.
  The patient can benefit from a reflexion period of of 7 days.
  In case of agreement, a first blood draw will take place before initiation of any treatment. Between D15 and D30 a second blood draw will be taken. Then a blood draw will be necessary every two months until recurrence or progression of the disease for a maximum of 22 months.

Eligibility: Inclusion Criteria:
  -  Patients in metastatic situation for a malignant melanoma inoperable stage IIIB or IIIC or stage IV
  -  In first line of treatment by a targeted therapy (only or in association) or immunotherapy
  -  Every histological types of cutaneous or mucous malignant melanoma (excepted choroid melanomas)
  -  The tumor must be mutates for BRAF or NRAS
  -  The mutation status must have been realized in the Laboratory Pathology Clinical and Experimental (LPCE) of the CHU de Nice analysis of the status on-site metastatic mutational and/or primitive tumor must
  -  Membership or beneficiary of the national insurance scheme
  Exclusion Criteria:
  -  Histories of cancer or other synchronous cancer
  -  Pregnant, breast-feeding Women. A pregnancy test will be practiced to the women old enough to procreate.
  -  Vulnerable People: adults under guardianship, patients deprived of freedom, minor

Relevance to patient case: not relevant
Patient case: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

Clinical trial: UV1 Vaccine With Pembrolizumab for Patients With Unresectable or Metastatic Melanoma

Summary: UV1 is a therapeutic cancer vaccine that has been explored in prostate and lung cancers, and in combination with ipilimumab in malignant melanoma. This study will explore the safety, tolerability and efficacy of UV1 administered with GM-CSF in melanoma patients who are also receiving pembrolizumab.


Eligibility: Key Inclusion Criteria:
  1. Stage IIIB, IIIC or IV melanoma
  2. Previously untreated and eligible for pembrolizumab treatment (prior treatment with BRAF and MEK inhibitors permitted) 3) Adequate blood, liver and kidney function 4) Consent to undergo tumor biopsies during the study
  Exclusion Criteria:
  1. Uveal or ocular malignant melanoma
  2. History of hematologic or primary solid tumor malignancy with the exception of patients in remission for at least 5 years, as judged by the investigator are allowed
  3. Prior systemic treatment for unresectable or metastatic melanoma. Exception: Prior treatment with BRAF and MEK inhibitors permitted. A washout period of at least 3-half-lives (median terminal half-life) prior to the first dose of trial treatment must have elapsed.
  4. Prior therapy with an anti-CTLA4, anti-PD-1, anti-PD-L1, anti-PD-L2 agent or oncolytic virus.
  5. Known hypersensitivity to GM-CSF
  6. Women who are breastfeeding, pregnant or expect to be pregnant during the study through 6 months after the last dose
  7. Men who plan to become a father during the study through 4 months after the last dose of study medication
  8. Known history of, or any evidence of active, non-infectious pneumonitis
  9. History of cardiac disease

Relevance to patient case: not relevant