araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

Clinical trial: MEK162 and RAF265 in Adult Patients With Advanced Solid Tumors Harboring RAS or BRAFV600E Mutations

Summary: This is a multi- center, open-label, dose finding, Phase Ib study to be conducted in two stages: a dose escalation part to determine the maximum tolerated dose (MTD) safety and tolerability of concurrent administration of MEK162 and RAF265, followed by an expansion part to further assess the safety and preliminary anti-tumor efficacy of this oral combination within two separate patient populations: i) patients with advanced solid tumors harboring BRAFV600E mutations or ii) patients with advanced solid tumors harboring RAS mutations.


Eligibility: Inclusion Criteria:
  Patients with histologically or cytologically confirmed and non-resectable advanced solid tumors for which no further effective standard therapy exists.
  -  The patients' tumors must contain documented activating somatic BRAFV600E* , NRAS or KRAS mutations (except for pancreatic cancer)
  -  All patients enrolled MUST provide fresh or archival tumor samples at baseline to enable central confirmation of BRAF or KRAS/NRAS mutations
  -  Measurable, or non-measurable but evaluable disease as determined by RECIST
  -  Adequate bone marrow function
  -  Adequate hepatic and renal function
  -  Adequate cardiovascular function
  -  Negative serum β HCG test (female patients of childbearing potential only) within 72 hrs prior to first dose
  Exclusion Criteria:
  -  Patients with a history of primary central nervous system tumors or brain metastases or who have signs/symptoms attributable to brain metastases and have not been assessed with radiologic imaging to rule out the presence of brain metastases
  -  Current evidence of retinal disease; or ophthalmopathy as assessed by ophthalmologic examination at baseline that would be considered a risk factor for CSR/RVO (e.g., optic disc cupping, visual field defects, IOP > 21 mm Hg)
  -  Impaired cardio-/vascular function or clinically significant cardiovascular diseases, including any of the following:
  -  History/evidence of acute coronary syndromes (including MI, unstable angina, CABG, coronary angioplasty, or stenting) ≤ 6 months prior to starting study drugs
  -  Thromboembolic event (DVT, CVA, PE) ≤ 6 months prior to starting study
  -  Symptomatic CHF, history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality
  -  Uncontrolled arterial hypertension, defined as BP > 140/100 mmHg (average of 3 consecutive readings)
  -  History of melena, hematemesis or hemoptysis within the last 3 months
  -  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)
  Other protocol-defined inclusion/exclusion criteria may apply

Relevance to patient case: possibly relevant
Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

Clinical trial: Safety, Pharmacokinetics and Pharmacodynamics of BKM120 Plus MEK162 in Selected Advanced Solid Tumor Patients

Summary: This is an open label, dose finding, phase Ib clinical trial to determine the maximum tolerated dose (MTD) and/or the recommended phase II dose (RP2D) of the orally administered phosphatidylinositol 3'-kinase (PI3K) inhibitor BKM120 in combination with the MEK1/2 inhibitor MEK162. This combination will be explored in patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) which has progressed on EGFR inhibitors and triple negative breast cancer, as well as pancreatic cancer, colorectal cancer, malignant melanoma, NSCLC, and other advanced solid tumors with KRAS, NRAS, and/or BRAF mutations. Dose escalation will be guided by a Bayesian logistic regression model with overdose control. At MTD or RP2D, two expansion arms will be opened in order to further assess safety and preliminary anti-tumor activity of the combination of BKM120 and MEK162.
  Study drugs will be administered once daily orally on a continuous schedule. A treatment cycle is defined as 28 days.


Eligibility: Inclusion Criteria:
  -  Histologically/ cytologically confirmed, advanced non resectable solid tumors
  -  Measurable or non-measurable, but evaluable disease as determined by RECIST
  Exclusion Criteria:
  -  Patients with primary CNS tumor or CNS tumor involvement.
  -  Diabetes mellitus
  -  Unacceptable ocular/retinal conditions

Relevance to patient case: possibly relevant
Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

Clinical trial: Ph I Ipilimumab Vemurafenib Combo in Patients With v-Raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF)

Summary: Treatment of subjects who have metastatic melanoma that expresses an activated mutant form of the BRAF oncogene (V600E) with a combination of the specific BRAF inhibitor, Vemurafenib, and the Cytotoxic T Lymphocyte Antigen 4 (CTLA-4) inhibitor mAb Ipilimumab will be safe and feasible and will show preliminary evidence of anti-tumor efficacy and survival in comparison to historical results following treatment with either agent alone.


Eligibility: For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.
  Inclusion Criteria:
  -  Metastatic melanoma with activating V600 BRAF mutation
  -  Measurable Tumor
  -  Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1
  Exclusion Criteria:
  -  Autoimmune disease
  -  Active Brain Metastasis (must be stable after radiation for at least one month)
  -  Prior therapy with immune stimulating agents

Relevance to patient case: possibly relevant
Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

Clinical trial: BRAF V600E Mutations In Papillary Thyroid Carcinoma

Summary: The purpose of this study is to determine whether BRAF V600E mutation in our patients with papillary thyroid cancer has an association with poor prognosis.

Detailed description: Papillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy and BRAF V600E mutation is the most common genetic alteration identified in PTC, ranging from 25 to 80%, with the average rate about 45%. Various studies demonstrated a relationship between BRAF V600E mutation and aggressive characteristics of the cancer, including the worse patient prognosis. But,there are no studies from Turkey regarding this topic. So the investigators will examine BRAF V600E mutation in our patients with PTC and try to assess the role of this mutation in prognosis and further management of the patients.

Eligibility: Inclusion Criteria:
  -  Patients with papillary thyroid cancer
  Exclusion Criteria:
  -  Patients who do not want to be a part of this study

Relevance to patient case: possibly relevant
Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

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: possibly relevant
Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

Clinical trial: First-line FOLFOXIRI Plus Bevacizumab in BRAF Mutant Metastatic Colorectal Cancer

Summary: The purpose of this study is to prospectively verify if FOLFOXIRI plus bevacizumab as first-line treatment could be considered a promising approach to improve the outcome of BRAF mutant metastatic colorectal cancer patients


Eligibility: Inclusion Criteria:
  -  Histologically confirmed colorectal adenocarcinoma;
  -  Availability of formalin-fixed paraffin embedded tumor block from primary and/or metastasis;
  -  BRAF V600E mutant status of primary colorectal cancer and/or related metastasis;
  -  Unresectable and measurable metastatic disease according to RECIST criteria;
  -  Male or female, aged > 18 years and < 75 years;
  -  ECOG PS < 2 if aged < 71 years;
  -  ECOG PS = 0 if aged 71-75 years;
  -  Life expectancy of more than 3 months;
  -  Adequate haematological function: ANC ≥ 1.5 x 10^9/L; platelets ≥ 100 x 10^9/L, Hb ≥ 9 g/dL;
  -  Adequate liver function: serum bilirubin ≤ 1.5 x ULN; alkaline phosphatase and transaminases ≤ 2.5 x ULN (in case of liver metastases ≤ 5 x ULN);
  -  Serum creatinine ≤ 1.5 x ULN;
  -  Previous adjuvant chemotherapy is allowed if more than 12 months have elapsed between the end of adjuvant therapy and first relapse;
  -  At least 6 weeks from prior extended radiotherapy and 4 weeks from surgery;
  -  Written informed consent to experimental treatment and molecular analyses.
  Exclusion Criteria:
  -  Presence or history of CNS metastasis;
  -  Serious, non-healing wound, ulcer, or bone fracture;
  -  Evidence of bleeding diathesis or coagulopathy;
  -  Uncontrolled hypertension;
  -  Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (CVA) (≤6 months before treatment start), myocardial infarction (≤ 6 months before treatment start), unstable angina, NYHA ≥ grade 2 chronic heart failure (CHF), uncontrolled arrhythmia;
  -  Current or recent (within 10 days prior to study treatment start) ongoing treatment with anticoagulants for therapeutic purposes;
  -  Chronic, daily treatment with high-dose aspirin (>325 mg/day);
  -  Symptomatic peripheral neuropathy ≥ 2 grade NCIC-CTG criteria;
  -  Active uncontrolled infections;
  -  Treatment with any investigational drug within 30 days prior to enrolment;
  -  Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of curatively treated basal and squamous cell carcinoma of the skin or in situ cancer of the cervix;
  -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start;
  -  Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome;
  -  Fertile women (< 2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception.

Relevance to patient case: possibly relevant
Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

Clinical trial: A Study of Vemurafenib in Participants With BRAF V600 Mutation-Positive Cancers

Summary: This open-label, multi-center study will assess the efficacy and safety of vemurafenib in participants with BRAF V600 mutation-positive cancers (solid tumors and multiple myeloma, except melanoma and papillary thyroid cancer) and for whom vemurafenib is deemed the best treatment option in the opinion of the investigator. Participants will receive twice daily oral doses of 960 mg vemurafenib until disease progression, unacceptable toxicity, or withdrawal of consent. The safety and efficacy of vemurafenib in combination with cetuximab in a subset of participants with colorectal cancer will also be assessed.


Eligibility: Inclusion Criteria:
  -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  -  Must have recovered from all side effects of their most recent systemic or local treatment
  -  Adequate hematological, renal and liver function
  For solid tumors only:
  -  Histologically confirmed cancers (excluding melanoma and papillary thyroid cancer) with a BRAF V600 mutation and that are resistant to standard therapy or for which standard or curative therapy does not exist
  -  Measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST)
  For multiple myeloma only:
  -  Confirmed diagnosis of multiple myeloma with a BRAF V600 mutation
  -  Must have received at least one prior systemic therapy for the treatment of multiple myeloma
  -  Treated with local radiotherapy
  -  Must have relapsed and/or refractory multiple myeloma with measurable disease
  Exclusion Criteria:
  -  Melanoma, papillary thyroid cancer or hematological malignancies (with the exception of multiple myeloma)
  -  Uncontrolled concurrent malignancy
  -  Multiple myeloma: solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia
  -  Active or untreated central nervous system (CNS) metastases
  -  History of or known carcinomatous meningitis
  -  Concurrent administration of any anti-cancer therapies other than those administered in this study
  -  Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that would, in the investigator's opinion, contraindicate participation in this study

Relevance to patient case: possibly relevant
Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

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: possibly relevant
Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

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: possibly relevant
Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

Clinical trial: A Phase I Study to Investigate the Safety, Tolerability and Pharmacokinetic Profile of of GSK2118436 in Japanese Subjects With BRAF Mutation Positive Solid Tumors

Summary: BRF116056 is the first clinical experience with GSK2118436, a BRAF inhibitor, in Japan. This study will be designed to assess safety, tolerability, single and repeat dose PK profile and preliminary efficacy of GSK2118436 in Japanese subjects with BRAF V600 mutation positive solid tumors using continuous daily dosing schedule.

Detailed description: BRF116056 is the first clinical experience with GSK2118436, a BRAF inhibitor, in Japan. This study will be designed to assess safety, tolerability, single and repeat dose PK profile and preliminary efficacy of GSK2118436 in Japanese subjects with BRAF V600 mutation positive solid tumors using continuous daily dosing schedule. Dose escalation of GSK2118436 will be performed according to a standard 3+3 dose-escalation design. GSK2118436 is given twice a day. However, to characterize the PK of GSK2118436 and its metabolites after single-dose administration, GSK2118436 will NOT be administrated for a week after the first administration. GSK2118436 continuous dosing will start after the 168-hour PK sample is obtained. Subjects may receive study treatment until disease progression, death or an unacceptable adverse event.

Eligibility: Inclusion Criteria:
  -  Histologically or cytologically confirmed diagnosis of a solid tumor that is not responsive to standard therapies or for which there is no approved or curative therapy.
  -  Subjects must have BRAF V600E or K mutant positive tumors.
  -  Women with reproductive potential must be willing to practice acceptable methods of birth control during the study and for up to 4 weeks after the last dose of study medication.
  -  Men with reproductive potential must be willing to practice acceptable methods of birth control during the study and for up to 16 weeks after the last dose of study medication.
  -  Must have adequate organ function.
  -  Must have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
  Exclusion Criteria:
  -  Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy or surgery).
  -  Use of an investigational anti-cancer drug within 28 days preceding the first dose of GSK2118436.
  -  A history of other malignancy. Subjects who have been disease-free for 5 years or subjects with a history of complete resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
  -  History of Human Immunodeficiency Virus (HIV) infection.
  -  Certain cardiac abnormalities.
  -  Pregnant or lactating female.

Relevance to patient case: possibly relevant