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

Clinical trial: BRAF-/MEK-Inhibition With Dabrafenib and Trametinib in Melanoma Patients

Summary: Adjuvant therapy with dabrafenib plus trametinib in melanoma was approved in 2018 by the EMA (EUropean Medicines Agency).
  The purpose of this non-interventional study is to assess the usage of adjuvant dabrafenib and trametinib in clinical practice, where the patient population may differ from study population.

Detailed description: Melanoma is a disease of significant metastatic potential if not detected very early. Oncogenic mutations in BRAF (B-Raf proto-oncogene, serine/threonine kinase) are found in approximately 40% of melanomas and result in constitutive activation of the MAPK (Mitogen-Activated Protein Kinase) pathway.
  Treatment with the BRAF inhibitor dabrafenib plus the MEK (Mitogen-activated protein kinase kinase) inhibitor trametinib showed improved overall survival in patients with unresectable or metastatic BRAF V600E/K-mutant melanoma (COMBI-d and COMBI-v studies). In an adjuvant setting treatment with dabrafenib and trametinib significantly reduced the risk of melanoma recurrence in patients with high-risk, stage III BRAF V600-mutant melanoma, with improvements in OS (Overall Survival), DMFS (Distant Metastasis Free Survival), and FFR (Freedom From Relaps) (COMBI-AD study). Based on these results, adjuvant dabrafenib plus trametinib therapy was approved in 2018 by the EMA.
  Compared to the metastatic situation, issues of compliance and treatment adherence may be more relevant in adjuvant treatments, as patients are free of disease and potentially cured even without adjuvant treatment. As the routine administration of drugs including dosing, treatment interruptions, and early termination in clinical practice may vary from procedures defined in clinical trials, this study aims to assess the usage of adjuvant dabrafenib and trametinib in the routine clinical setting.

Eligibility: Inclusion Criteria:
  -  Patients with complete surgical resection of histologically confirmed AJCC (American Joint Committee on Cancer) (8th edition) clinical stage III (IIIA, IIIB, IIIC, IIID) melanoma, for whom a decision for adjuvant treatment with dabrafenib and trametinib has been made before entering the study.
  -  V600E/K mutation-positive cutaneous melanoma
  -  Adjuvant treatment with combination therapy of Dabrafenib (Tafinlar®) and Trametinib (Mekinist®) as indicated in the SmPC (Summary of Product Characteristics) and by prescription, that has been started no longer that 4 weeks before inclusion of the patient into the study or which will be initiated directly after inclusion
  -  Age ≥ 18 years
  -  Signed written informed consent
  Exclusion Criteria:
  -  Lack of basic demographics and staging information
  -  Current or planned participation within a clinical trial. The participation in a follow-up phase of a clinical trial without active intervention is allowed.
  -  Current or planned treatment of another tumor disease except keratoacanthoma, squamous cell or basal cell carcinoma of the skin

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

Clinical trial: Registry Study of Neoadjuvant Chemoradiation & Transplant for Cholangiocarcinoma Patients

Summary: This is an observational study intended to validate results of a previous study done at the Mayo Clinic. Patients are treated with combination chemotherapy and radiation and maintained on oral Xeloda until they can receive liver transplant. A staging laparotomy is performed before chemoradiation in order to identify patients who will most benefit from the treatment and to improve outcomes.


Eligibility: Inclusion Criteria:
  1. Diagnosis of cholangiocarcinoma that has been established preoperatively by at least one of the following criteria:
  1. A positive brush cytology or biopsy result obtained at the time of cholangiography;
  2. Fluorescence in situ hybridization demonstrating aneuploidy;
  3. A serum CA 19-9 value greater than 100 U/mL in the presence of a radiographically characteristic malignant stricture in the absence of cholangitis.
  2. Tumor/stricture is above the cystic duct and is unresectable.
  3. A suitable candidate for orthotopic liver transplantation as judged by the liver transplant team. All 3 treatment modalities are not needed to confirm eligibility for this registry trial.
  4. >/= 18 years of age.
  5. Willing and able to provide written informed consent.
  Exclusion Criteria:
  1. Intrahepatic metastasis or other metastatic disease (except peri-hilar nodes).
  2. Prior treatment for this disease (including attempts at resection, irradiation, or chemotherapy)

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

Clinical trial: Safety Study of PLX4032 in Patients With Solid Tumors

Summary: The primary objective of this FIH study is to assess the safety and pharmacokinetics of PLX4032 in patients with solid tumors. The secondary objective is to assess the pharmacodynamic activity in paired biopsy specimens obtained from patients with malignant melanoma who have the V600E BRAF oncogenic mutation.

Detailed description: Activating mutations of the BRAF gene have been observed in a variety of cancers, including 55-68% of malignant melanomas. In general, oncogenic mutations of BRAF correlate with a poor outcome. PLX4032 is a compound that selectively inhibits oncogenic B-Raf kinase.
  Two extension cohorts of patients with confirmed V600E mutations will be recruited, consisting of advanced melanoma and metastatic colorectal carcinoma.

Eligibility: Inclusion Criteria:
  -  Solid tumors confirmed histologically whose tumors are refractory to standard therapy, or for whom standard or curative therapy does not exist
  -  Patients from whom paired melanoma biopsies are planned must have a V600E+ BRAF mutation confirmed prior to the administration of PLX4032
  -  Previous chemotherapy, immunotherapy, or radiation therapy must have been completed at least 2 weeks prior to starting PLX4032 therapy, and all associated toxicity must be resolved prior to administration of PLX4032
  -  Patients in the Extension cohorts (melanoma or adenocarcinoma of the colon or rectum) must have both a V600E+ BRAF mutation and measurable disease (by RECIST V 1.0 criteria) prior to the administration of PLX4032. All patients enrolled must provide archival or fresh melanoma tumor biopsy for confirmation of V600E+ BRAF mutation status by TaqMan assay
  -  ECOG performance status 0 or 1
  -  Life expectancy ≥ 3 months
  -  Adequate hematologic, hepatic, and renal function
  Exclusion Criteria:
  -  Brain metastases that are progressing or have been documented to be stable for less than 3 months, or for which systemic corticosteroids are required
  -  Investigational drug use within 28 days of the first dose of PLX4032
  -  Uncontrolled intercurrent illness
  -  Refractory nausea and vomiting, malabsorption, or significant bowel resection that would preclude adequate absorption

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

Clinical trial: Study to Test Genetic Alterations Among Different Dermoscopic Types of Melanocytic Nevi.

Summary: This project is a multicenter study in which we will investigate a dual concept of nevogenesis. Study location is the Department of Dermatology at the Medical University of Graz in collaboration with centers in Austria (Vienna), Italy (Naples, Benevento, Modena), Spain (Barcelona) and the United States (New York).
  The hypothesis is that small congenital melanocytic nevi (CMN), "early" acquired melanocytic nevi in childhood (AMN) and dermal nevi, all dermatoscopically characterized by globular pattern, belong to the same spectrum of genetically determined melanocytic proliferations that develop due to endogenous pathways, in contrast to "true" acquired melanocytic nevi, dermatoscopically showing reticular pattern, that develop due to exogeneous factors such as UV-exposure.

Detailed description: The investigations to this study will verify whether small CMN, "early" AMN and dermal nevi, characterized by globular pattern differ in their genetic alterations compared to reticular typed nevi. It will be expected that globular typed nevi and eventually dermal nevi lack B-RAF mutations whereas reticular nevi show alterations in the B-RAF gene. Study location: Graz

Eligibility: Inclusion Criteria:
  -  Healthy individuals aged 9 to 80 years showing one or more dermoscopically benign nevi with either uniform globular-cobblestone pattern or reticular pattern or a combination of both types
  Exclusion Criteria:
  -  Children under the age of 9 years
  -  Pregnant woman
  -  Patients with atypical nevi (i.e., melanoma cannot be clinically ruled out)
  -  Patients with immunosuppression
  -  Patients with sun exposure 4 weeks before enrollment

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

Clinical trial: Use of Fenofibrate for Primary Biliary Cirrhosis

Summary: This is a pilot study to evaluate the safety and efficacy of fenofibrate on patients with primary biliary cirrhosis who have an incomplete response to ursodeoxycholic acid.

Detailed description: This is a multicenter open label pilot study to evaluate the efficacy of fenofibrate in 20 patients with PBC treated for 1 year. A randomized design would not be feasible at this stage of the research. Two sites are enrolling patients: University of Florida, Gainesville, and Mayo Clinic Rochester, with the first as the coordinating site. The total number of patients to start treatment will not exceed 20. Our endpoints are 1) surrogate markers of disease activity -serum alkaline phosphatase and immunoglobulin M; 2) a well validated prognostic index -Mayo risk score and 3) the NIDDK quality of life questionnaire.

Eligibility: Inclusion Criteria:
  -  Established diagnosis of PBC by serological (positive antimitochondrial antibodies) and/or histological evidence (diagnostic liver biopsy)
  -  Previous treatment with UDCA 13-15 mg/kg/day for at least 1 year
  -  Persistent elevation of serum alkaline phosphatase ≥ 2 times the upper limit of normal on two separate measurements
  -  Female patients of childbearing age should have a pregnancy test done within -days of the beginning of this trial, and should agree to be on adequate contraception throughout the study period
  -  Signed informed consent after careful review of the information and study details by one of the investigators
  Exclusion Criteria
  -  Hypersensitivity to fenofibrate
  -  Prisoners and institutionalized subjects
  -  Pregnant or nursing women
  -  Anticipated need for liver transplantation in one year (estimated one year survival < 80%) as determined by the Mayo risk score. The Mayo risk score takes into account the patient's age, serum bilirubin, albumin and prothrombin time, as well as presence or absence of peripheral edema.
  -  Recipients of liver transplantation
  -  Recurrent variceal hemorrhage, uncontrolled encephalopathy or refractory ascites
  -  Co-existing liver diseases, such as primary sclerosing cholangitis, acute or chronic hepatitis, alcoholic liver disease, choledocholithiasis, autoimmune hepatitis, cholangiocarcinoma
  -  Acute or chronic renal failure
  -  Known history of cholecystitis with intact gallbladder
  -  Current use of statins, as the concomitant use of fibrates and statins would increase the risk of toxicity

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

Clinical trial: Coregistration of 18F-FDG-PET and MRI in the Staging of Potentially Resectable Hilar Cholangiocarcinoma: a Pilot Study

Summary: To evaluate the feasibility and performance of coregistered 18F-FDG-PET/MRI in the staging of potentially respectable hilar cholangiocarcinoma.


Eligibility: Inclusion Criteria:
  -  Hilar cholangiocarcinoma assessed by conventional imaging modalities (triphasic CT scan of the liver) and thought to be potentially resectable.
  Exclusion Criteria:
  -  Biliary drain inserted.
  -  Contraindication for MRI.
  -  Pregnant or breast-feeding.
  -  Uncontrolled diabetes (over 9.7 mmol/L).

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

Clinical trial: S-1 and Photodynamic Therapy in Cholangiocarcinoma

Summary: In patients with unresectable perihilar cholangiocarcinoma, photodynamic therapy with biliary stent has been known for palliation of jaundice and improving survival. But most of therapeutic effects were expected to delay bile duct obstruction rather than to decrease the tumor. Recently orally available chemotherapeutic agent, S-1 was reported as effective in patients with bile duct adenocarcinoma. The investigators' aims of study evaluate the combined effect of photodynamic therapy and S-1.

Detailed description: In patients with unresectable perihilar cholangiocarcinoma, photodynamic therapy with biliary stent has been known for palliation of jaundice and improving survival. But most of therapeutic effects were expected to delay bile duct obstruction rather than to decrease the tumor. Recently orally available chemotherapeutic agent, S-1 was reported as effective in patients with bile duct adenocarcinoma. The investigators' aims of study evaluate the combined effect of photodynamic therapy and S-1.

Eligibility: Inclusion Criteria:
  -  Histologic or cytologic diagnosis of cholangiocarcinoma
  -  Not eligible for curative surgery
  -  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 ≧75,000/ul)
  -  Consent this study in letter
  Exclusion Criteria:
  -  Another neoplasia
  -  Porphyria
  -  Pregnant or breastfeeding women

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

Clinical trial: Photodynamic Therapy (PDT) Trial for Palliation of Cholangiocarcinoma

Summary: This research study is a phase III double arm, multicenter, randomized controlled clinical trial comparing endoscopic retrograde cholangiopancreatography (ERCP) and stenting plus photodynamic therapy (PDT) versus ERCP with stenting alone in adult patients with unresectable cholangiocarcinoma.
  The study objectives are to investigate the efficacy of photodynamic therapy (PDT) in increasing the survival time of patients with unresectable cholangiocarcinoma and to assess the effect of PDT on both cholestasis and health-related quality of life (HRQoL).

Detailed description: The study objectives are to investigate the efficacy of photodynamic therapy (PDT) in increasing the survival time of patients with unresectable cholangiocarcinoma and to assess the effect of PDT on both cholestasis and health-related quality of life (HRQoL).

Eligibility: Inclusion Criteria:
  -  Patient is age 18 years or older
  -  Patient is diagnosed with non-resectable cholangiocarcinoma, as determined by CT within 30 days of enrollment and CT shows Bismuth Tumor Stage as: IIIa, IIIb, IV (Bismuth tumor stage I and II are not eligible to participate)
  -  Patients must have adequate organ and marrow function as defined below:
  -  Patient's INR ≤ 2 within 30 days of treatment
  -  Patient's platelets > 50,000/cmm within 30 days of treatment
  -  Patient's Absolute Neutrophil Count (ANC) > 1,500/cmm within 30 days of treatment
  -  Patient's creatinine ≤ 3 mg/dL within 30 days of treatment
  -  Patient has the ability to understand and the willingness to comply with the study procedures and provide written informed consent to participate in the study
  Exclusion Criteria:
  -  Patient was diagnosed with cholangiocarcinoma more than 3 months ago
  -  Patient has any metastatic disease
  -  Patient has acute porphyria
  -  Subjects exhibiting neurologic or cutaneous symptoms will undergo urinary delta-aminolevulinic acid and porphobilinogen dosage tests to determine severity.
  -  Patient is pregnant (Women of child bearing age must have a negative pregnancy test prior to registration and must agree to use adequate contraception during study therapy)
  -  Patient has a concurrent non solid malignancy

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

Clinical trial: Comparison of AZD6244 in Combination With Dacarbazine Versus (vs) Dacarbazine Alone in BRAF Mutation Positive Melanoma Patients

Summary: To assess the efficacy in terms of overall survival of AZD6244 in combination with dacarbazine, compared with dacarbazine alone, in first line patients with BRAF mutation positive advanced cutaneous or unknown primary melanoma


Eligibility: Inclusion Criteria:
  -  Histological or cytological confirmation of advanced (inoperable stage III and stage IV) cutaneous or unknown primary melanoma
  -  Tumor sample confirmed as BRAF mutation positive
  Exclusion Criteria:
  -  Diagnosis of uveal or mucosal melanoma
  -  Any prior Investigational therapy comprising inhibitors of Ras, Raf or MEK
  -  Having received an investigational drug within 30 days of starting treatment, or have not recovered from side effects of an investigational drug

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 Previously Treated Patients With Metastatic Melanoma

Summary: This open-label single arm study will assess the efficacy, safety and tolerability of Vemurafenib in previously treated patients with metastatic melanoma. Patients will receive oral Vemurafenib [RG7204; PLEXXIKON: PLX4032] at a dose of 960 mg b.i.d. continuously until disease progression or withdrawal from study and will be assessed at regular intervals for tumour response and tolerability. Target sample size is <100 patients.


Eligibility: Inclusion Criteria:
  -  adult patients >/=18 years of age
  -  histologically confirmed metastatic melanoma (Stage IV, AJCC)
  -  patients must have completed and failed at least one prior standard of care regimen (e.g. DTIC, temozolomide, etc.)
  -  BRAF V600E positive mutation (by Roche CoDx BRAF mutation assay)
  -  measurable disease by RECIST criteria
  -  negative pregnancy test and, for fertile men and women, effective contraception during treatment and for 6 months after completion
  Exclusion Criteria:
  -  active CNS metastases on CT/MRI within 28 days prior to enrollment
  -  history of or known carcinomatous meningitis
  -  previous treatment with BRAF (sorafenib allowed) or MEK inhibitor
  -  cardiac dysrhythmias >2 NCI CTCAE or treatment with drugs with dysrhythmic potential
  -  uncontrolled hypertension(>150/100mmHg) despite optimal medical therapy
  -  infectious disease including HIV, HBV and HCV

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

Clinical trial: Study to Determine the Effectiveness of GSK1120212 in BRAF Mutation-positive Melanoma Previously Treated With or Without a BRAF Inhibitor

Summary: MEK113583 is a Phase II open-label, multi-site study to investigate the objective response rate, safety, and pharmacokinetics of GSK1120212 in subjects with BRAF mutation-positive melanoma who were previously treated with or without a BRAF inhibitor. GSK1120212 is a potent and highly selective inhibitor of MEK activation and kinase activity.


Eligibility: Inclusion Criteria:
  -  Metastatic cutaneous melanoma that was previously treated with: (Cohort A) a BRAF inhibitor either with or without other prior therapy. (Cohort B) at least 1 prior chemotherapy or immunotherapy, without treatment with a BRAF inhibitor.
  -  Documented positive BRAF mutation (V600E, V600K, or V600D).
  -  Subjects must provide archived tumor tissue or undergo fresh tumor biopsy prior to enrollment.
  -  The subject must have a radiographically measurable tumor.
  -  The subject is able to carry out daily life activities without significant difficulty (ECOG performance status score of 0 or 1).
  -  Able to swallow and retain oral medication.
  -  Sexually active subjects must use acceptable methods of contraception during the course of the study.
  -  Adequate organ system function and blood cell counts.
  Exclusion Criteria:
  -  The subject has had major surgery or received certain types of cancer therapy within 21 days before starting the study.
  -  Previous treatment with a MEK inhibitor.
  -  Current use of a prohibited medication listed in the protocol.
  -  Uncontrolled glaucoma.
  -  Brain metastasis, unless previously treated with surgery or stereotactic radiosurgery, and the disease has been stable for at least 2 months prior to enrollment.
  -  Current severe or uncontrolled systemic disease.
  -  History of clinically significant heart, lung, or eye/vision problems.
  -  Significant unresolved side effects from previous anti-cancer therapy.
  -  The subject is pregnant or breastfeeding.

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

Clinical trial: Glivec/Gleevec Pediatric (Age 1 to Less Than 4) PK Study in CML, Ph+ ALL Patients and Other Glivec/Gleevec® Indicated Hematological Disorders.

Summary: This study will assess the pharmacokinetics of imatinib in pediatric patients ages 1 to <4 years of age to help develop dosing regimens


Eligibility: Inclusion Criteria:
  1. Patients must be 1 to less than 4 years of age at study entry
  2. Written informed consent must be signed by the patient's parent or legal guardian.
  3. Patients must have the diagnosis of CML or Ph+ ALL
  4. Lansky score must be ≥ 50 (Table7-2)
  5. Patient must have adequate end organ function as defined by
  -  Total bilirubin < 1.5 x ULN
  -  SGPT (ALT) and SGOT (AST) < 2.5 x UNL
  -  Creatinine < 1.5 x ULN
  Exclusion Criteria:
  1. Patients who have received drugs a) known to be metabolized by CYP3A4 or 3A5, b) are CYP inhibitors and inducers, within 2 weeks prior to Visit 2 (except for imatinib)
  2. Patients who previously received radiotherapy to ≥ 25% of the bone marrow, with the exception of patients who received total body radiation as part of a preparatory regimen for hematopoetic stem cell transplant (HSCT)
  3. Patients receiving antibacterial and antipyretic medication to treat active infection
  4. Patients with International normalized ratio (INR) or partial thromboplastin time (PTT) > 1.5 x ULN, with the exception of patients on treatment with oral anticoagulants
  5. Patients whose parents or legal guardians, in the opinion of the Investigator, were unlikely to comply with the protocol or safety monitoring requirements
  Other protocol-defined inclusion/exclusion criteria may apply

Relevance to patient case: not relevant