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

Clinical trial: A Pharmacokinetic/Pharmacodynamic Study of RO5185426 in Previously Treated Patients With Metastatic Melanoma

Summary: This open-label study will assess the pharmacokinetics, efficacy and safety of RO5185426 administered as 240mg tablets in previously treated patients with metastatic melanoma. Patients will be randomized to receive one of four dose-levels of RO5185426 [RG7204; PLEXXIKON; PLX4032] orally twice daily on days 1 to 15 (morning dose). Starting on day 22, treatment with RO5185426 may be resumed at a dose of 960 mg twice daily and continued until disease progression. Target sample size is <100 patients.


Eligibility: Inclusion Criteria:
  -  adult patients, >/=18 years of age
  -  histologically confirmed metastatic melanoma, stage IIIc or IV (AJCC)
  -  failure of at least one prior standard of care regimen
  -  positive for BRAF V600E mutation (by Roche CoDx BRAF mutation assay)
  -  ECOG performance status 0 or 1
  -  adequate hematologic, renal and liver function
  Exclusion Criteria:
  -  active CNS lesions on CT/MRI within 28 days prior to enrollment
  -  history of spinal cord compression o carcinomatous meningitis
  -  anticipated or ongoing anti-cancer therapies other than those administered in this study
  -  previous treatment with BRAF inhibitor (sorafenib allowed) or MEK inhibitor
  -  severe cardiovascular disease within 6 months prior to study
  -  previous malignancy within the past 5 years except for basal or squamous cell carcinoma of the skin, melanoma in-situ and carcinoma in-situ of the cervix

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

Clinical trial: A Study of RO5212054 (PLX3603) in Participants With BRAF V600-Mutated Advanced Solid Tumors

Summary: This open-label, multi-center study will evaluate the safety, tolerability, and pharmacokinetics of RO5212054 [PLX3603] in participants with BRAF V600-mutated advanced solid tumors. Cohorts of participants will receive escalating oral doses of RO5212054. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.


Eligibility: Inclusion Criteria:
  -  Advanced solid tumor
  -  Dose-escalation phase: Histologically confirmed, newly diagnosed or relapsed/ refractory unresectable American Joint Committee on Cancer (AJCC) Stage IIIC or IV disease
  -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  -  Adequate liver, renal and bone marrow function
  Exclusion Criteria:
  -  Participants for whom standard therapy exists and is considered appropriate by the investigator
  -  Prior treatment with an inhibitor of BRAF (sorafenib allowed)
  -  Active Central nervous system (CNS) lesions, or history of or known carcinomatous meningitis
  -  Treatment with any chemotherapy, radiotherapy, immunotherapy or investigational agent within 28 days prior to first dose of study drug
  -  Anticipated or ongoing anti-cancer therapies other than those administered in this study
  -  Serious cardiovascular illness within the 6 months prior to study drug administration

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

Clinical trial: A Study of GSK2118436 in BRAF Mutant Metastatic Melanoma

Summary: BRF113710 is a Phase II, single-arm, open-label study to assess the efficacy, safety, and tolerability of GSK2118436 administered twice daily as a single agent in subjects with BRAF mutant metastatic melanoma. Subjects will receive 150 mg of GSK2118436 twice daily and continue on treatment until disease progression, death, or unacceptable adverse event.


Eligibility: Inclusion Criteria:
  -  Must be at least 18 years of age
  -  Must have histologically confirmed cutaneous metastatic melanoma (Stage IV) that is BRAF mutation-positive (V600 E/K) as determined via central testing with a BRAF mutation assay.
  -  Is treatment naive or has received prior treatment for metastatic melanoma.
  -  Must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
  -  Women of child-bearing potential must have a negative pregnancy test within 14 days prior to the first dose of study treatment.
  -  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 Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
  -  Adequate organ function.
  Exclusion Criteria:
  -  Previous treatment with a BRAF or MEK inhibitor.
  -  Cancer therapy (chemotherapy with delayed toxicity, radiation therapy, immunotherapy, biologic therapy, or major surgery) within the last 3 weeks; chemotherapy regimens without delayed toxicity within the last 2 weeks; or use of any investigational anti-cancer or other drug within 28 days or 5 half-lives, whichever is longer, preceding the first dose of GSK2118436.
  -  A history of known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection.
  -  History or evidence of brain metastases on MRI or head CT if MRI is not able to be performed.
  -  History of other malignancy. Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
  -  Certain cardiac abnormalities.

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

Clinical trial: A Study to Investigate Safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) of BKM120 Plus GSK1120212 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 recommended phase II dose (RP2D) and schedule for the PI3K (Phosphatidylinositol 3-Kinase) inhibitor BKM120 given in combination with the MEK inhibitor GSK1120212 in patients with selected, advanced solid tumors. The focus will be on tumors with RAS/RAF mutations and on triple negative breast cancer.
  Both study drugs will be administered once daily orally on a continuous schedule, a treatment cycle is defined as 28 days.
  Cohorts of at least 3 and up to a maximum of 6 patients eligible for the dose-determining set will be enrolled per dose combination below the MTD. The MTD is defined as the highest drug dosage not causing in the first cycle of treatment medically unacceptable, dose-limiting toxicity (DLT) in more than 33% of the treated patients.. At least 12 patients will be required at MTD and 6 patients at RP2D level to allow the evaluation of the combination's safety and pharmacokinetics or pharmacodynamics.
  Upon declaration of MTD and/or RP2D, patients will be enrolled to an expansion part of the study, to further assess safety, as well as to learn more about the efficacy of the study drug combination.
  -  Expansion Arm 1 will consist of approximately 15 patients with RAS or BRAF mutant advanced NSCLC
  -  Expansion Arm 2 will consist of approximately 15 patients with RAS or BRAF-mutant ovarian cancer
  -  Expansion Arm 3 will consist of approximately 15 patients with RAS or BRAF-mutant pancreatic cancer


Eligibility: Inclusion Criteria:
  -  histologically/ cytologically confirmed, advanced non resectable solid tumors
  -  Measurable or non-measurable, but evaluable disease as determined by RECIST 1.0
  Exclusion Criteria:
  -  Patients with primary Central Nervous System (CNS) tumor or CNS tumor involvement.
  -  Clinically manifested diabetes mellitus - Unacceptable ocular/retinal conditions
  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: A Pharmacokinetic and Metabolism Study of 14C-labeled RO5185426 on Patients With Metastatic Melanoma

Summary: This open-label, non-randomized study will assess the mass balance, metabolism, routes and rates of elimination as well as efficacy and safety of RO5185426 (RG7204; PLEXXIKON; PLX4032) in previously treated or untreated patients with metastatic melanoma. Patients will receive continuous twice daily oral treatment with RO5185426. On Day 15, a 14C-labeled dose will be administered. Anticipated time on study treatment is until disease progression occurs.


Eligibility: Inclusion Criteria:
  -  Adult patients, >/= 18 years of age
  -  Histologically confirmed metastatic melanoma, surgically incurable and unresectable Stage IIIc or IV (AJCC)
  -  Prior treatment for metastatic melanoma allowed; >/= 28 days must be elapsed since previous systemic treatment prior to first administration of study drug
  -  Positive BRAF V600E mutation result (by Roche CoDx test)
  -  ECOG performance status 0-1
  -  Adequate hematologic, renal and liver function
  -  Body Mass Index (BMI) 18 to 32 kg/m2 inclusive
  Exclusion Criteria:
  -  Active CNS lesions
  -  History of or known spinal cord compression, or carcinomatous meningitis
  -  Anticipated or ongoing administration of any anticancer therapies other than those administered in this study
  -  Refractory nausea or vomiting, or other medical conditions that are capable of altering the absorption, metabolism or elimination of the study drug
  -  Known clinically significant active infection
  -  Known HIV positivity or AIDS-related illness, active HBV, or active HCV
  -  Previous malignancy within the past 5 years, except for basal or squamous cell carcinoma of the skin, melanoma in situ, and carcinoma in situ of the cervix
  -  Clinically significant cardiovascular disease or incident within the 6 months prior to study drug administration
  -  Patients who have had at least one dose of study drug (RO5185426 or comparator) in a clinical trial that includes RO5185426

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

Clinical trial: A Study Comparing GSK2118436 to Dacarbazine (DTIC) in Previously Untreated Subjects With BRAF Mutation Positive Advanced (Stage III) or Metastatic (Stage IV) Melanoma

Summary: BRF113683 is a Phase III, randomized, open-label study comparing the efficacy, safety, and tolerability of GSK2118436 to dacarbazine (DTIC), in subjects with BRAF mutant advanced (Stage III) or metastatic (Stage IV) melanoma. Subjects will be randomized to receive 150 mg of GSK2118436 twice daily or 1000 mg/m2 DTIC every 3 weeks and continue on treatment until disease progression, death, or unacceptable adverse event. Subjects who progress on DTIC will be allowed to crossover to an optional extension arm of the study to receive GSK2118436.


Eligibility: Inclusion Criteria:
  -  Adults at least 18 years of age
  -  Has advanced (unresectable Stage III) or metastatic (Stage IV) melanoma that is BRAF mutation positive (V600E)
  -  Is treatment naive for advanced (unresectable) or metastatic melanoma, with the exception of Interleukin 2 (IL-2) which is allowed.
  -  Has measurable disease according to RECIST 1.1 criteria.
  -  Women of child-bearing potential must have a negative pregnancy test within 14 days prior to the first dose of study treatment.
  -  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).
  -  Evidence of active central nervous system (CNS) disease.
  -  Previous treatment for metastatic melanoma, including treatment with BRAF or MEK inhibitor.
  -  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

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

Clinical trial: Biomarkers in Predicting Response to Cetuximab in Patients With Advanced Colorectal Cancer

Summary: RATIONALE: Studying samples of tissue in the laboratory from patients who received cetuximab may help doctors understand and predict how well patients will respond to treatment.
  PURPOSE: This research study is studying biomarkers in predicting response to cetuximab in patients with advanced colorectal cancer.

Detailed description: OBJECTIVES:
  Primary
  -  To determine, among patients with advanced CRC, whether the effect of treatment (cetuximab vs bevacizumab) on progression-free survival (PFS) depends on tumor BRAF V600E mutational status.
  Secondary
  -  To study the relationships between tumor BRAF V600E mutational status, OS, and tumor response.
  OUTLINE: This is a multicenter study.
  Previously collected formalin-fixed and paraffin-embedded baseline tumor samples are analyzed for BRAF V600E mutation. Mutation status is correlated with clinical response and outcome data from patients enrolled on CALGB-C80405.

Eligibility: DISEASE CHARACTERISTICS:
  -  Participation in CALGB-C80405
  -  Have KRAS WT or KRAS mut tumor
  -  Randomized to treatment with either bevacizumab or cetuximab alone
  -  Patients randomized to the combination therapy are not eligible
  -  Available specimens at the PCO for BRAF mutation detection
  -  Patient consent for use of samples

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

Clinical trial: A Study of RO5185426 in Patients With Metastatic Melanoma

Summary: This is an open-label, non-comparative, multicenter, expanded access study of RO5185426 in patients who have received prior systemic therapy for metastatic melanoma and who have no other satisfactory treatment options.


Eligibility: Inclusion Criteria:
  -  Histologically confirmed metastatic melanoma with documented BRAF V600E mutation, determined by the cobas BRAF V600 mutation test
  -  Patients with either measurable or non-measurable disease
  -  Adequate recovery from most recent systemic or local treatment for metastatic melanoma
  -  Adequate organ function
  -  For women of childbearing potential, agreement to the use of two acceptable methods of contraception, including one barrier method, during the study and for 6 months after discontinuation of RO5185426
  -  For men with female partners of childbearing potential, agreement to use a latex condom, and to advise their female partner to use an additional method of contraception during the study and for 6 months after discontinuation of RO5185426
  -  Negative serum or urine pregnancy test within 7 days of commencement of treatment in premenopausal women. Women who are either surgically sterile or have been post-menopausal for at least 1 year are eligible to participate in this study
  -  Agreement not to donate blood or blood products during the study and for at least 6 months after discontinuation of RO5185426; for male patients, agreement not to donate sperm during the study and for at least 6 months after discontinuation of RO5185426
  Exclusion Criteria:
  -  Pregnant or breast-feeding
  -  Concurrent anti-tumor therapy
  -  Uncontrolled medical illness
  -  History of congenital prolonged QT syndrome or patients with a mean QTc interval greater than 470 milliseconds at baseline, or ongoing grade 2 or greater cardiac arrhythmia

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

Clinical trial: Endoscopic Bipolar Radiofrequency Probe (ENDOHPB) in the Management of Unresectable Bile Duct and Pancreatic Cancer

Summary: The purpose of this study is to assess safety and ability of the endoscopic bipolar radiofrequency ablation (RFA) probe (ENDOHPB) to produce an improvement in the management of cancer of the bile duct or the pancreatic duct. By using radiofrequency (RF) energy to heat the tissue in the duct prior to insertion of the stent, the surrounding tissue becomes coagulated and this may delay tumour growth and the time before the stent lumen becomes blocked. Thereby, allowing increased periods between the need for intervention and further stent deployment. The study will look to see if the ENDOHPB is able to keep the stent open longer and perhaps decrease the number of invasive procedures for occluded (blocked) stents.

Detailed description: Only a small proportion of patients with biliary obstruction caused by cholangiocarcinoma or pancreatic cancer are suitable for surgical resection. As the cancer grows, it blocks the drainage of the bile ducts that carry digestive juices from the gall bladder and pancreas to the small intestine. Blocked drainage causes abdominal pain, bloating, and nausea. ERCP (endoscopic retrograde cholangiopancreatography) is often prescribed. ERCP with stent placement is the standard medical procedure for people with bile duct and pancreatic cancer.
  The purpose of this study is to assess safety and ability of the endoscopic bipolar radiofrequency ablation (RFA) probe (ENDOHPB) to produce an improvement in the management of cancer of the bile duct or the pancreatic duct. By using radiofrequency (RF) energy to heat the tissue in the duct prior to insertion of the stent, the surrounding tissue becomes coagulated and this may delay tumour growth and the time before the stent lumen becomes blocked. Thereby, allowing increased periods between the need for intervention and further stent deployment. The study will look to see if the ENDOHPB is able to keep the stent open longer and perhaps decrease the number of invasive procedures for occluded (blocked) stents.
  The objectives are:
  • To assess assess the safety and effectiveness of an endoscopic bipolar radiofrequency catheter (EndoHPB) in the management of unresectable cholangiocarcinoma and pancreatic cancer

Eligibility: Inclusion Criteria:
  -  Either gender greater than or equal to 18 years of age.
  -  Pancreatic cancer or cholangiocarcinoma unsuitable for surgical resection. Criteria of unresectability being based on 1) metastatic disease or 2) locally advanced.
  -  Biliary obstruction
  -  Blocked self expanding mesh metal stent (SEMS)
  -  Subjects capable of giving informed consent
  -  Life expectancy of at least 3 months
  Exclusion Criteria:
  -  Cardiac Pacemaker
  -  Patient unstable for endoscopy
  -  Inability to give informed consent
  -  Uncorrected coagulopathy

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

Clinical trial: A Study of LGK974 in Patients With Malignancies Dependent on Wnt Ligands

Summary: This primary purpose of this study is to find the recommended dose of LGK974 as a single agent and in combination with PDR001 that can be safely given to adult patients with selected solid malignancies for whom no effective standard treatment is available.


Eligibility: Inclusion Criteria:
  Diagnosis of locally advanced or metastatic cancer that has progressed despite standard therapy or for which no effective standard therapy exists and histological confirmation of one of the following diseases indicated below:
  Single Agent Dose escalation part:documented B-RAF mutant colorectal cancer or pancreatic adenocarcinoma. In addition, tumors of any histological origin with documented genetic alterations upstream in the Wnt signaling pathway are eligible with prior agreement with Novartis.
  Single Agent Dose expansion part: documented B-RAF mutant colorectal cancer with documented RNF43 mutation and/or RSPO fusion or pancreatic adenocarcinoma with documented RNF43 mutation. In addition, patients with tumors of any histological origin with documented genetic alterations upstream in the Wnt signaling pathway (e.g. RNF43 or RSPO fusion) are eligible with prior agreement with Novartis
  LGK974 with PDR001: Dose escalation: patients with the following cancers that were previously treated with anti-PD-1 therapy and whose best response on that therapy was progressive disease (i.e. primary refractory): melanoma, lung SCC, HNSCC. Patients with esophageal SCC, cervical SCC or TNBC who are either naïve or primary refractory to prior anti-PD-1 therapy.
  LGK974 with PDR001: Dose expansion: patients with pancreatic cancer, or TNBC, or melanoma, or head and neck cancer.
  Exclusion Criteria:
  -  Impaired cardiac function
  -  Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of oral LGK974 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)
  -  Brain metastases that have not been adequately treated
  -  Malignant disease other than that being treated in this study
  -  Laboratory abnormalities as specified in the protocol
  -  Osteoporosis, severe or untreated osteopenia
  -  Bone fractures within the past year
  -  Pathologic bone fracture
  -  Active, known or suspected autoimmune disease or severe hypersensitivity reactions to other monoclonal antibodies
  Other protocol-defined inclusion/exclusion criteria may apply

Relevance to patient case: possibly relevant