araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 51-year-old female with papillary thyroid carcinoma; genetic feature: BRAF (V600E)

Clinical trial: Study of Nivolumab Given Sequentially With Ipilimumab in Subjects With Advanced or Metastatic Melanoma (CheckMate 064)

Summary: The purpose of this study is to evaluate the safety and efficacy of a sequential combination therapy of Nivolumab and Ipilimumab

Detailed description: In order to evaluate the potential synergistic activity of nivolumab and ipilimumab and also because there may be differences in biology between tumors which are stable or responding to therapy and those that are clinically progressing, this study, CA209064, looked at two sequential combination regimens in which the second agent is administered immediately after a pre-specified duration of therapy with the first agent and not delayed until the time of progression after the first agent. This sequential study design looked at pharmacodynamic changes during treatment with one agent which may predict clinical activity to subsequent treatment with the alternate agent. This was done because it has not been scientifically proven whether or not the order in which nivolumab and ipilimumab are given is clinically important.

Eligibility: For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com
  Inclusion Criteria:
  -  Histologically confirmed unresectable Stage III or IV melanoma
  -  Treatment-naive or experienced disease recurrence or progression during or after one prior systemic regimen for advanced disease
  -  Measurable disease by Computed Tomography/Magnetic resonance imaging (CT/MRI) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
  -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  -  Known BRAF V600 mutation status or consent to BRAF V600 mutation testing
  -  Sufficient tumor tissue accessible for baseline and post-treatment biopsies.
  Exclusion Criteria:
  -  Active central nervous system (CNS) metastases
  -  Carcinomatous meningitis
  -  Active, known or suspected autoimmune disease
  -  Condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization
  -  Prior therapy with anti-Programmed Death-1 (PD1), anti-Programmed Death-Ligand 1 (PD-L1), anti-PD-L2, anti-CD137, or anti-CTLA-4 (cytotoxic T lymphocyte antigen 4) antibody
  -  Prior treatment with other immunotherapies
  -  Prior therapy with BRAF inhibitor within 6 weeks of enrollment

Relevance to patient case: not relevant
Patient case: 51-year-old female with papillary thyroid carcinoma; genetic feature: BRAF (V600E)

Clinical trial: A Screening Study to Detect BRAF V600 Mutation-Positive Patients For Enrollment Into Clinical Research Studies of Zelboraf (Vemurafenib)

Summary: This is a screening study to detect BRAF V600 mutation-positive patients for enrollment into clinical research studies of Zelboraf (vemurafenib). Tumor samples will be collected and analyzed from eligible patients with solid tumors (other than metastatic melanoma or papillary thyroid cancer) or multiple myeloma. All institutions with identified patients as defined by this screening protocol will have potential access to the separate vemurafenib protocol MO28072.


Eligibility: Inclusion Criteria:
  -  Histologically confirmed solid tumors (excluding melanoma and papillary thyroid cancer) or multiple myeloma refractory to standard therapy or for which standard or curative therapy does not exist or is not considered appropriate by the investigator
  -  Patients with multiple myeloma must have received at least one line of prior systemic therapy for the treatment of multiple myeloma
  Exclusion Criteria:
  -  Eastern Cooperative Oncology Group (ECOG) performance status > 2
  -  Uncontrolled concurrent malignancy
  -  Active or untreated CNS metastases
  -  History of known carcinomatous meningitis
  -  Prior treatment with a BRAF or MEK inhibitor (prior sorafenib is allowed)
  -  Uncontrolled, severe medical illness or condition as defined in protocol MO28072

Relevance to patient case: not relevant
Patient case: 51-year-old female with papillary thyroid carcinoma; genetic feature: BRAF (V600E)

Clinical trial: Optimized Treatment and Regression of HBV-induced Liver Fibrosis

Summary: Patients with chronic hepatitis B histologically confirmed of liver fibrosis S2/S3 (similar to metavir F2/F3, Ishak 2/3/4) are randomly assigned in a 1:1 ratio. One arm is entecavir alone for 2 years; the other is entecavir alone for the first 0.5 year, entecavir plus pegylated interferon (peg-IFN) for 1 year, entecavir for another additional 0.5 year. Patients will be assessed at baseline, at every six months for blood count, liver function test, HBVDNA, AFP, prothrombin time, thyroid function, liver ultrasonography, and Fibroscan. The second liver biopsy will be performed to evaluate regression rate of liver fibrosis 1.5 years after initial therapy.


Eligibility: Inclusion Criteria:
  1. Ages from 18 to 65 years old;
  2. Male or female;
  3. Treatment-naive patients with chronic HBV-induced fibrosis S2/S3 (similar to F2/F3, Ishak 2/3/4), who consent to undergo liver biopsy before and after treatment;
  4. Patients with HBeAg-positive, HBVDNA>2×10<4> IU/ml or with HBeAg-negative, HBVDNA>2×10<3> IU/ml;
  5. Agree to be follow-up regularly;
  6. signature of written inform consent.
  Exclusion Criteria:
  1. Patients with decompensated cirrhosis: including ascites, hepatic encephalopathy, esophageal varices bleeding or other complications of decompensated cirrhosis or hepatocelluar carcinoma;
  2. Patients who are allergic to entecavir, interferon, or their components, and those considered not suitable for medications used in this study;
  3. Patients coinfection with HCV or HIV, alcoholic liver disease, autoimmune liver disease, genetic liver disease, drug-induced liver injury, severe non-alcoholic fatty liver disease or other chronic liver diseases;
  4. Patients with baseline AFP level higher than 100 ng/ml and possible malignant lesion on image, or AFP level higher than 100 ng/ml for continuous three months;
  5. Creatinine >1.5×ULN;
  6. Patients with other uncured malignant tumors;
  7. Patients with severe diseases of heart, lung, kidney, brain, blood system or other organs;
  8. Patients with severe neurological or psychological disease (e.g. epilepsy, depression, mania and schizophrenia);
  9. Patients with poorly controlled diabetes, hypertension or thyroid disease;
  10. Patients with any other reasons not suitable for the study.

Relevance to patient case: not relevant
Patient case: 51-year-old female with papillary thyroid carcinoma; genetic feature: BRAF (V600E)

Clinical trial: Percutaneous Ethanol Injection for Primary Papillary Thyroid Microcarcinoma

Summary: We assess the effectiveness of percutaneous ethanol ablation for the treatment of thyroid cancer.

Detailed description: We hypothesize that percutaneous ethanol ablation (PEA) for primary papillary thyroid microcarcinoma (PTMC) has equivalent oncologic outcomes to current treatment options including observation, thyroid lobectomy and total thyroidectomy. In addition, we hypothesize that it will yield superior long-term quality of life, including measures of pain, voice, and cosmesis than standard surgical therapy (total thyroidectomy). If our hypotheses are correct, the findings of this study have the potential to fundamentally change clinical management of this group of patients.
  This study was changed from its initial design: a 2 arm study comparing PEA to surgery (Amended April 30, 2015). The change in design was made based on several discussions within Yale Endocrine Surgery, with patients diagnosed with PTMC, and knowledge of other institutions performing PEA for PTMC as standard of care.
  The study team had been contacted by numerous potential subjects interested in PEA who were unwilling to be randomized to surgery. Because patients interested in PEA appeared to be firmly against the idea of thyroidectomy, we believed that we would be unable to enroll sufficient patients to this study as the protocol originally stood.

Eligibility: Inclusion Criteria:
  -  Age 18 years and older
  -  Diagnosis: single, cytology-proven papillary thyroid carcinoma measuring 1 cm or less in diameter (microcarcinoma, T1a), without visible extrathyroidal extension, and with negative central and lateral neck lymph nodes by ultrasound
  Exclusion Criteria:
  -  Patient refusal to participate
  -  History of prior thyroid or parathyroid surgery
  -  Previous recurrent laryngeal nerve injury
  -  Inability to make decisions or comply with follow up
  -  Co-existing indication for thyroidectomy
  -  Aggressive cytological or molecular features
  -  Multifocal papillary thyroid carcinoma
  -  Pregnant or breast-feeding
  -  Anatomically unfavorable location of the tumor (proximity to recurrent laryngeal nerve or trachea)
  -  Documented or suspected distant metastasis
  -  History of radiation to neck or face
  -  Family history of thyroid cancer

Relevance to patient case: not relevant
Patient case: 51-year-old female with papillary thyroid carcinoma; genetic feature: BRAF (V600E)

Clinical trial: A Study of MEHD7945A and Cobimetinib in Patients With Locally Advanced or Metastatic Cancers With Mutant KRAS

Summary: This open-label, multicenter, global Phase Ib study will evaluate the safety, tolerability and pharmacokinetics of intravenous (IV) dosing of MEHD7945A in combination with oral dosing of cobimetinib in patients with locally advanced or metastatic solid tumors that carry a Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) mutation and for which standard therapies do not exist, have proven ineffective or intolerable or are considered inappropriate. The study comprises a dose-escalation (Stage 1) and an indication-specific cohort expansion stage (Stage 2).


Eligibility: Inclusion Criteria:
  -  Locally advanced or metastatic solid KRAS-mutant tumors, for which standard therapies do not exist, have proven ineffective or intolerable or are considered inappropriate
  -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  -  Evaluable disease or disease measurable per modified Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
  -  Consent to provide archival tumor tissue for biomarker testing
  -  Additionally, for patients who are considered for enrollment into the indication specific expansion cohorts in Stage 2, the current cancer must be either KRAS-mutant colorectal cancer (CRC) or KRAS-mutant non-small cell lung cancer (NSCLC)
  Exclusion Criteria:
  -  History of prior significant toxicity from another MEK pathway inhibitor or combination of another MEK and epidermal growth factor receptor (EGFR) inhibitor requiring discontinuation of treatment
  -  Previous treatment with a combination of a MEK inhibitor with an EGFR inhibitor (applies only to the indication specific expansion cohorts in Stage 2)
  -  Allergy or hypersensitivity to components of the cobimetinib formulations
  -  History of severe (Grade 3 or 4) allergic or hypersensitivity reaction to therapeutic antibodies that required discontinuation of therapy
  -  History of interstitial lung disease (ILD)
  -  Known severe ulcer disease
  -  History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, central serous chorioetinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration
  Patients will be excluded if they currently have either of the following conditions which have been identified as risk factors for CSCR:
  -  Uncontrolled glaucoma with intraocular pressure greater than (>) 21 millimeters of mercury (mm Hg)
  -  Grade greater than equal to (>=) 3 hypertriglyceridemia

Relevance to patient case: not relevant
Patient case: 51-year-old female with papillary thyroid carcinoma; 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: not relevant
Patient case: 51-year-old female with papillary thyroid carcinoma; 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: not relevant
Patient case: 51-year-old female with papillary thyroid carcinoma; 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: not relevant
Patient case: 51-year-old female with papillary thyroid carcinoma; 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: not relevant
Patient case: 51-year-old female with papillary thyroid carcinoma; genetic feature: BRAF (V600E)

Clinical trial: An Observational Study in Differentiated Thyroid Cancer Which is Radioactive Iodine (RAI) Refractory to Assess the Use of Multikinase Inhibitors

Summary: The purpose of the study is to assess the use of Multikinase Inhibitors (MKIs) in the treatment of patients with a progressive differentiated thyroid carcinoma (DTC) refractory to radioactive iodine (RAI) who do not have any symptoms.

Detailed description: The primary objective of this study is to compare time to symptomatic progression (TTSP) from study entry in asymptomatic patients with RAI-refractory progressive DTC for whom there is a decision to initiate MKIs at study entry with that of asymptomatic patients with RAI-refractory progressive DTC for whom there is a decision to not initiate MKIs at study entry.

Eligibility: Inclusion Criteria:
  -  Histologically/cytologically documented DTC (papillary, follicular, Hurthle cell, and poorly differentiated carcinoma)
  -  DTC refractory to RAI
  -  Radiological progression and preferably according to RECIST 1.1
  -  No symptoms due to DTC
  -  >/=1cm diameter of lesion confirmed by radiological exam
  -  Life expectancy of at least 6 months
  Exclusion Criteria:
  -  Plan to be treated according to a clinical trial protocol for intervention including a locoregional therapy or systemic therapy
  -  Previous treatment with MKIs for advanced disease
  -  Hospice patients

Relevance to patient case: not relevant