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

Clinical trial: S-1 in Combination With Abraxane in Treating Cholangiocarcinoma

Summary: This phase II study was designed to evaluate the efficacy and safety of S-1 plus Abraxane as second-line treatment for cholangiocarcinoma.

Detailed description: There are no standard second-line treatment for cholangiocarcinoma, new therapies are needed. The efficacy of S-1 as first-line treatment for cholangiocarcinoma was confirmed in several studies. The IMPACT study showed that Abraxane plus gemcitabine provide better survival than gemcitabine alone. Since cholangiocarcinoma displayed similar sensitivity to chemotherapy which was used in pancreatic carcinoma, we assume that S-1 plus Abraxane is effective and safe in treating cholangiocarcinoma.

Eligibility: Inclusion Criteria:
  -  Histologic or cytologic diagnosis of cholangiocarcinoma
  -  Not eligible for curative surgery
  -  Progressed after first-line gemcitabine-based chemotherapy
  -  Eastern Cooperative Oncology Group (ECOG) performance status of 2 or better
  -  No serious or uncontrolled concomitant medical illness
  -  Adequate bone marrow function (absolute neutrophil count ≧1,500 ul, platelet count ≧90,000/ul), hemoglobin: > or equal to 8 mg/dL, total bilirubin: < or equal to 1.5 X institutional upper limit of normal, calculated creatinine clearance greater than or equal to 60 mL/min (calculated by the Cockcroft and Gault method).
  Exclusion Criteria:
  -  Uncontrolled infection or severe active comorbid disease
  -  Previous malignancy in the past five years, excluding nonmelanoma skin cancers and in situ cervical, bladder or uterine cancer
  -  Pregnancy or lactating women

Relevance to patient case: not relevant
Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

Clinical trial: Phase 1 Safety and Tolerability of MEDI4736 in Combination With Dabrafenib and Trametinib or With Trametinib Alone

Summary: The purpose of this study is to determine the maximum tolerated dose and characterize the safety profile of durvalumab (MEDI4736) in combination with dabrafenib and trametinib or with trametinib alone in participants with metastatic or unresectable melanoma with BRAF-mutation positive or wild-type (WT) BRAF, respectively.

Detailed description: This is a multicenter, open-label study with a dose escalation phase followed by an expansion phase of durvalumab administered in combination with dabrafenib and trametinib or with trametinib alone in participants with BRAF V600 mutation-positive and WT unresectable or metastatic melanoma, respectively.

Eligibility: Inclusion Criteria:
  -  Adults >= 18 years old
  -  Histologically confirmed cutaneous melanoma that is either Stage IIIc (unresectable) or Stage IV (metastatic) and determined to be BRAF V600E or V600K mutation-positive (cohort A) or mutation-negative (cohorts B and C)
  -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  -  Measurable disease by radiographic or physical examination
  -  Adequate organ and marrow function
  -  Willingness to provide consent for biopsies positive or BRAF WT measurable disease and adequate organ and marrow function
  Exclusion Criteria:
  -  Prior treatment with a BRAF inhibitor or MEK inhibitor
  -  Any prior Grade >= 3 immune-related adverse event while receiving immunotherapy
  -  Active or prior documented autoimmune disease within the past 2 years
  -  History of or current risk for retinal vein occlusion (RVO) or central serous retinopathy (CSR)
  -  History of or current cardiovascular risk including myocardial infarction, >= Class II congestive heart failure, uncontrolled arrhythmias, or refractory hypertension
  -  Active, untreated central nervous system (CNS) metastases
  -  Women who are pregnant or lactating

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

Clinical trial: Study to Evaluate Treatment of Dabrafenib Plus Trametinib in Subjects With BRAF Mutation-Positive Melanoma That Has Metastasized to the Brain

Summary: This is a multi-cohort, open label, Phase II study with Dabrafenib (GSK2118436) and Trametinib (GSK1120212) combination therapy in subject with BRAF mutation-positive melanoma that has metastasized to the brain. This study will evaluate the safety and efficacy of 4 cohorts. Cohorts will consist of; V600 E, D, K, R mutations, metastases to the brain, symptomatic and asymptomatic, with or without prior local (brain) therapy, with or without prior local (brain) therapy, and range of ECOG scores from 0-2.


Eligibility: Inclusion Criteria:
  -  ECOG Performance Status range of 0-2
  -  Histologically confirmed cutaneous metastatic melanoma of V600 E, K, D or R.
  -  May be systemic naïve or received up to two previous systemic treatment regimens for metastatic melanoma.
  -  Must be able to undergo MRI and have at least one measurable intracranial lesion for which specific criteria have to be met.
  Exclusion Criteria:
  -  Prior treatment with any BRAF inhibitor or any mitogen-activated protein/extracellular signal-regulated kinase inhibitor.
  -  Anti-cancer therapy or investigational anti-cancer therapy or chemotherapy without delayed toxicity within treatment specific timeframe.
  -  Treatment with stereotactic radiosurgery or treatment with whole-brain radiation within treatment specific timeframe.
  -  Any presence of leptomeningeal disease or any parenchymal brain metastasis
  -  History of another malignancy, some exceptions may apply.
  -  A history or evidence of cardiovascular risk- specific criteria have to be met
  -  A history or current evidence/risk of retinal vein occlusion or retinal pigment epithelial detachment - specific criteria have to be met.

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

Clinical trial: Efficacy and Safety of LGX818 in Patients With Advanced or Metastatic BRAF V600 Mutant NSCLC

Summary: This is an open-label, multi-center, single arm phase II study to evaluate the efficacy and safety of novel BRAF (B-raf murine sarcoma viral oncogene homolog B1) inhibitor encorafenib (LGX818) when used as single agent in patients with advanced or metastatic (stage IIIB or IV) BRAF V600 mutant NSCLC. Patients must have progressed on or after at least one previous systemic, anti-cancer therapy for locally advanced or metastatic NSCLC.


Eligibility: Inclusion Criteria:
  -  Presence of BRAF V600E mutation in tumor tissue
  -  Histologically or cytologically confirmed diagnosis of Stage IIIB or IV NSCLC
  -  At least one measurable lesion as defined by RECIST v1.1
  -  Patients must have progressed during or after at least one previous systemic, anti-cancer treatment for locally advanced or metastatic NSCLC.
  -  Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) performance status 0-2
  Exclusion Criteria:
  -  Patients with symptomatic Central Nervous System (CNS) metastases
  -  History of leptomeningeal metastases
  -  Prior therapy with a BRAF inhibitor
  -  Patients taking prohibited medication listed in the protocol
  -  Presence or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy within the past 3 years.
  -  Impaired cardiovascular function or clinically significant cardiovascular diseases
  -  Pregnant or lactating women or woman of childbearing potential

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

Clinical trial: A Phase II, Single Arm Study of BGJ398 in Patients With Advanced Cholangiocarcinoma

Summary: This is a multi-center, open label, single arm phase II study evaluating BGJ398 anti-tumor activity in advanced or metastatic cholangiocarcinoma patients with Fibroblast Growth Factor receptor (FGFR) genetic alterations.

Detailed description: Adult patients with histologically or cytologically confirmed advanced or metastatic cholangiocarcinoma with FGFR genetic alterations who have evidence of radiologic progression following a cisplatin-and gemcitabine-containing regimen for advanced disease or a gemcitabine-containing regimen for those who are considered intolerant to cisplatin will be enrolled. Approximately 55 adult patients over age 18, both male and female will be enrolled. Of these 55 patients, 40 patients will have cholangiocarcinoma with identified FGFR2 gene fusions and up to 15 patients may have other FGFR genetic alterations. All patients will receive oral BGJ398, once daily, on a three weeks on (21 days), one week off (7 days) schedule. One treatment cycle will consists of 28 days.

Eligibility: Inclusion criteria:
  - Adult patients with histologically or cytologically confirmed cholangiocarcinoma at the time of diagnosis.
  Patients with cancers of the gallbladder or ampulla of Vater are not eligible.
  - Patients must have received at least one prior regimen containing gemcitabine with or without cisplatin for advanced/ metastatic disease. Patient should have evidence of progressive disease following prior regimen, or if prior treatment discontinued due to toxicity must have continued evidence of measurable or evaluable disease.
  Exclusion criteria:
  -  Prior or current treatment with a MEK or selective FGFR inhibitor
  -  insufficient organ function
  -  Absolutely Neutrophil Count (ANC) < 1,000/mm3 [1.0 x 109/L]
  -  Platelets < 75,000/mm3 [75 x 109/L]
  -  Hemoglobin < 109.0 g/dL
  -  Total bilirubin > 1.5x ULN
  -  Aspartate aminotransferase/glutamic oxaloacetic transaminase/GOT (AST/SGOT) and Alanine aminotransferase/glutamic pyruvic transaminase/GPT (ALT/SGPT) > 2.5x ULN (AST and ALT) > 5x upper limit of normal (ULN) in the presence of liver metastases)
  -  Serum creatinine > 1.5x ULN and a calculated or measured creatinine clearance < 45 mL/min
  -  Inorganic phosphorus outside of normal limits
  -  Total and ionized serum calcium outside of normal limits
  Other protocol-defined inclusion/exclusion criteria may apply.

Relevance to patient case: not relevant
Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

Clinical trial: Treatment for Bile Duct Cancer in the Liver

Summary: The current standard treatment of inoperable intrahepatic cholangiocarcinoma (bile duct cancer in the liver) is chemotherapy, which is of limited efficacy. The use of selective internal radiotherapy treatment (SIRT-Y90) is proven efficacious in patients with intra-heptic tumor. Previous experience with SIRT is safe in patients with intrahepatic cholangiocarcinoma. This study aims to study the benefits of sequential administration of SIRT followed by standard chemotherapy for treatment of inoperable intrahepatic cholangiocarcinoma.


Eligibility: Inclusion Criteria:
  -  Age>18 years
  -  Histological or cytological diagnosis of cholangiocarcinoma
  -  Disease not amenable to surgery
  -  Predominant disease load in the liver (in case of extra-hepatic involvement, only patients with lymph nodes metastases are allowed)
  -  Naïve to locoregional or systemic treatment (but patients who develop recurrent disease after surgery are suitable)
  -  ECOG PS 0-1
  -  At least one measurable disease lesion according to RECIST v 1.1
  -  Life expectancy of 12 weeks or longer
  -  Adequate hematological, renal and hepatic function
  -  Platelet ≥100 x 109
  -  ANC ≥ 1.5 x 109
  -  Bilirubin ≤ 30µmol/L
  -  Albumin ≥ 30g/L
  -  ALT ≤ 3 ULN
  -  INR ≤ 1.5
  -  Serum creatinine ≤ 1.5 x ULN
  Exclusion Criteria:
  -  Prior malignancy except cervical carcinoma-in-situ or treated basal cell carcinoma. Any cancers treated curatively > 5 years prior to study entry are permitted.
  -  Patients with extra-hepatic disease other than regional lymph node metastases.
  -  Evidence of ascites or cirrhosis, as determined by clinical or radiologic assessment
  -  Biliary obstruction with no possibility of drainage
  -  Non-malignant disease that would render the patient unsuitable for treatment according to the protocol
  -  Prior treatment of chemotherapy for the cholangiocarcinoma
  -  Prior radiation therapy to the upper abdomen
  -  Complete thrombosis of the main portal vein
  -  Tumor volume > 50% of the normal liver volume
  -  Allergy to non-ionic contrast agents

Relevance to patient case: not relevant
Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

Clinical trial: The Oncopanel Pilot (TOP) Study

Summary: The BCCA Oncopanel is a clinical assay being developed to determine genotype status of a prospectively defined set of genes.
  The purpose of this pilot study is to assess the feasibility and effect on clinical-decision-making of the Oncopanel test. Eligible patients are those with advanced lung, colorectal, melanoma and GIST cancers and patients with diagnosed malignancies being considered for clinical trials.

Detailed description: Somatic mutations in solid tumors represent an established means of characterizing malignancies for prognostic, diagnostic and therapeutic purposes. Mutations in EGFR, KRAS, BRAF, and KIT and PDGFRA genes direct therapy in patients with advanced lung, colorectal, melanoma, and GIST tumors, respectively. Known or novel mutations in other genes may also be of clinical significance but are not identified by current genotyping offered to BC Cancer Agency (BCCA) patients. Furthermore, numerous candidate genes have been implicated as potential prognostic and predictive biomarkers in patients with solid tumours. As such, the Oncopanel is a clinical assay being developed to determine genotype status of a prospectively defined set of genes. The following clinically relevant set of genes and exons are included in the Oncpanel: KRAS, EGFR, BRAF, NRAS and HRAS, PIK3CA Signal Transduction Pathway Genes, RAS-RAF-MEK-MAPK Pathway, HER2, IDH1 and IDH2, ALK, TP53, c-KIT, STAT1&3 and PDGFRA. Additional testing on the tumour material will also include analysis of specific gene variants associated with adverse events or response to therapy.
  Numerous studies have documented the presence of circulating tumour DNA (ctDNA) among patients with advanced and early stage malignancies (20-22). The ability to diagnose standard cancer mutations with a blood-based assay (a "liquid biopsy") has not yet been established but presents obvious advantages. The emergence of "resistance" mutations arising in the metastatic tumor or throughout the course of therapy is well documented (21, 22). A blood biopsy may represent more accurate determination of the tumor's genetic features than archival DNA specimen. Adequate tissue specimens can be difficult to obtain from some patients with diagnosed malignancies, particularly lung cancer. A blood biopsy may represent a less invasive and timelier means of diagnosing both standard and translational cancer mutations.

Eligibility: Patients with archival tumor tissue and a known history of invasive malignancies are eligible if they meet one or more of the following criteria:
  -  Advanced colorectal cancer and eligible for standard KRAS testing,
  -  Advanced non-small cell lung cancer and eligible for standard EGFR testing,
  -  Advanced melanoma and eligible for standard BRAF testing,
  -  Gastrointestinal stromal tumors (GISTs) eligible for standard c-KIT and PDGFRA testing,
  -  Being considered for potential eligibility in clinical trial.

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

Clinical trial: Phase I-II Study With Tumor Molecular Pharmacodynamic (MPD) Evaluation and Pharmacokinetics of PD-0332991 in Patients Suffering Metastatic Melanoma

Summary: An open label multicentre, phase I-II study with tumour molecular pharmacodynamics (MPD) evaluation and pharmacokinetics of PD-0332991 added to vemurafenib in patients suffering metastatic melanoma with BR.
  The main objective is to establish the Maximum Tolerated Dose (MTD) of PD-0332991 when added to standard vemurafenib therapy (960 mg BID). The estimated MTD is defined as the dose of PD-0332991 combined with vemurafenib that will be associated with a prespecified proportion of patients experiencing a Dose-Limiting Toxicity (DLT), ie, 1/3.


Eligibility: Inclusion Criteria:
  -  Age > 18 years
  -  Stage IV or un-resectable stage III melanoma
  -  Presence of BRAF V600E/K mutation and CDNKN2A loss and expression of Rb using immunohistochemistry in a recent metastatic sample (< 6 months)
  -  A previous exposure to BRAF inhibitor or combination of BRAF and MEK inhibitors therapy is allowed unless it has been stopped more than 3 months before study enrolment(This will defined the two strata of the trial)
  -  No previous therapy by MEK inhibitor unless associated with BRAF inhibitors
  -  No previous therapy with the AKT/PI3K pathway inhibitor
  -  Patients should have a tumour available for repeated biopsies for pharmacodynamics evaluation
  -  Life expectancy of > 3 months
  -  ECOG performance status <2
  -  Signed informed consent
  -  Patient with health insurance coverage
  -  No patient under guardianship or curators
  Exclusion Criteria:
  -  Inadequate hepatic function defined as serum bilirubin>25 μmol/l, transaminases > 3.0 times the upper limit of normal (ULN) or 5ULN in cases of liver metastases;
  -  Inadequate bone marrow function defined as absolute neutrophil count<1500/mcl, platelets<150000/mcl and haemoglobin<8g/dL
  -  Inadequate renal function with serum creatinine>2.0mg/dl) and /or creatinine clearance< 60 ml/min
  -  Untreated brain metastases : Patients with brain metastases will be eligible if they have completed treatment 1 months prior to the start of study medication, have discontinued corticosteroid treatment for these metastases for at least 5 days, and are neurologically asymptomatic
  -  Myocardial infarct or unstable angina within the past 6 months
  -  Concomitant take of drugs known to be strong inhibitor or inducers of CYP314
  -  HIV positive.
  -  Chemotherapy, immunotherapy within 4 weeks
  -  Drugs interfering with PD-0332991 and vemurafenib metabolism
  -  Malabsorption syndrome or other condition that would interfere with enteral absorption
  -  Congenital long QT syndrome or screening QTc > 470 msec
  -  Need for chronic corticosteroid therapy of ≥10 mg of prednisone per day

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

Clinical trial: Study of Trametinib and Nab-paclitaxel in Patients With Melanoma

Summary: This study will investigate the combination of two drugs, trametinib and nab-paclitaxel, in patients with advanced unresectable or metastatic melanoma. Each drug has shown activity in trials of patients with melanoma. However, the combination of these two drugs has not been studied. In this trial the investigators will determine the maximum dose of the drug combination to be administered to patients with advanced unresectable or metastatic melanoma and examine the safety profile of the drug combination.

Detailed description: While treatment for melanoma has evolved in the last few years, advanced/metastatic melanoma remains an aggressive disease with poor prognosis. Trametinib and nab-paclitaxel have demonstrated single-agent activity in Phase III trials of patients with melanoma. The investigators propose to investigate this drug combination in patients with advanced unresectable or metastatic melanoma. This open-label Phase I study is designed to determine the maximum tolerated dose (MTD), recommended Phase II dose (RP2D), and safety profile of trametinib and nab-paclitaxel given in combination. Patients with melanoma and known BRAF mutation status will receive escalating doses of trametinib and nab-paclitaxel to determine the MTD. Once the MTD is determined an additional 6 patients will be treated at the MTD to establish the dose for future studies.

Eligibility: Inclusion Criteria:
  -  Adults (≥18 years) with histologically or cytologically-confirmed advanced unresectable or metastatic melanoma. BRAF mutation-positive and wild-type tumors are allowed.
  -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  -  Adequate hematologic, renal, and hepatic function
  -  Life expectancy ≥12 weeks
  -  Any pre-existing neuropathy must be <grade 2 per Common Technology Criteria for Adverse Events (CTCAE) version 4.0
  Exclusion Criteria:
  -  More than 1 prior cytotoxic chemotherapy regimen in the metastatic setting
  -  Prior MEK inhibitor therapy (prior BRAF inhibitor allowed)
  -  Prior nab-paclitaxel (prior taxane allowed)
  -  Use of an investigational anti-cancer drug within 21 days or 5 half-lives (whichever is shorter) prior to first dose. A minimum of 10 days after termination of investigational drug is required. Any drug-related toxicity should have resolved to Grade 1 or baseline.
  -  Symptomatic or untreated brain metastases
  -  History of retinal vein occlusion (RVO)

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

Clinical trial: APPLICATION OF MOLECULAR TECHNIQUES FOR IMPROVING THE DIAGNOSIS AND TREATMENT OF NODULAR THYROID LESIONS.

Summary: To determine the improvement in diagnosis of papillary carcinoma by detecting mutation V600E BRAF in retrospective cases with inconclusive cytologic diagnosis (categories III, IV and V of Bethesda System)

Detailed description: Aim of the study To determine the improvement in diagnosis of papillary carcinoma by detecting mutation V600E BRAF in retrospective cases with inconclusive cytologic diagnosis (categories III, IV and V of Bethesda System).
  Design: Retrospective observational study. Scope: The study will be peformed at the Pathology Service, from cytological samples and paraffin file post-diagnosis. Mutations are detected by pyrosequencing technique.
  Subject of study:
  Cases with histological diagnosis of papillary carcinoma (CP) and previous cytological diagnosis in groups III, IV and V Bethesda, collected between October 1989 and July 2014 in Corporació Parc Taulí.
  Methodology:
  -  Identification of cases
  -  Detection of BRAF V600E mutation, initially in histological material from the surgical specimen, and if present, detection in cytological material.
  The statistical analysis will use SPSS. Univariate and bivariate analysis will be done. Results will be presented in the form of frequency tables and percentages for qualitative variables and by average, median and standard deviation for quantitative variables. Pearson chi-square or Fisher's exact test will be applied. The Student t test or the Mann-Whitney test will be performed for quantitative variables.

Eligibility: Inclusion Criteria:
  -  Cases with histological diagnosis of papillary carcinoma (CP) and previous cytological diagnosis in groups III, IV and V Bethesda, collected between October 1989 and July 2014 in Corporació Parc Taulí
  Exclusion Criteria:
  -  Non available cytological or histological material

Relevance to patient case: possibly relevant