araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 57-year-old male with melanoma; genetic feature: BRAF (V600E), PTEN loss of function

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

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


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

Relevance to patient case: not relevant
Patient case: 57-year-old male with melanoma; genetic feature: BRAF (V600E), PTEN loss of function

Clinical trial: miRNA Machinery in Melanoma, Melanoma Metastases and Benign Melanocytic Naevi

Summary: MicroRNAs (miRNAs) are very small endogenous RNA molecules about 22-25 nucleotides in length, capable of post-transcriptional gene regulation. miRNAs bind to their target messenger RNAs (mRNAs), leading to cleavage or suppression of target mRNA translation based on the degree of complementarity. miRNAs have recently been shown to play pivotal roles in diverse developmental and cellular processes and linked to a variety of skin diseases and cancers. In the present study, the investigators examines the expression profiles of miRNA machinery components such as miRNA maturation and transport factors, microprocessor complex and RISC subunits in cutaneous melanoma, cutaneous melanoma metastases and benign melanocytic nevi.

Detailed description: Patients with cutaneous melanoma, cutaneous melanoma metastases and benign melanocytic nevi were included in the study. Punch biopsies were harvested from the center of the tumors. The miRNA machinery components were detected by quantitative real-time reverse transcriptase polymerase chain reaction.

Eligibility: Inclusion Criteria:
  -  cutaneous melanoma
  -  cutaneous melanoma metastases
  -  benign melanocytic nevi
  Exclusion Criteria:
  -  other forms of malignancy

Relevance to patient case: not relevant
Patient case: 57-year-old male with melanoma; genetic feature: BRAF (V600E), PTEN loss of function

Clinical trial: Study of Ipatasertib or GDC-0980 With Abiraterone Acetate Versus Coralie in Participants With Castration-Resistant Prostate Cancer Previously Treated With Docetaxel Chemotherapy

Summary: This multicenter, international, Phase Ib/II trial consists of two stages: a Phase Ib, open-label stage in which the recommended Phase II dose will be determined for ipatasertib and GDC-0980 in combination with abiraterone and prednisone/prednisolone and a Phase II, 3-arm, double-blind, randomized comparison of ipatasertib with abiraterone and prednisone/prednisolone versus placebo with abiraterone and prednisone/prednisolone.


Eligibility: Inclusion Criteria:
  -  Histologically confirmed metastatic or advanced prostate adenocarcinoma that has been previously treated with docetaxel and has progressed during treatment of at least one hormonal therapy
  -  Two rising PSA levels greater than or equal to (>/=) 2 ng/mL measured >/= 1 week apart or radiographic evidence of disease progression in soft tissue or bone
  -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening
  -  Adequate hematologic and organ function
  -  Documented willingness to use an effective means of contraception
  Exclusion Criteria:
  -  History of Type I or Type II diabetes mellitus requiring insulin
  -  New York Heart Association Class III or IV heart failure or Left ventricular ejection fraction < 50% or ventricular arrhythmia requiring medication
  -  Significant atherosclerotic disease, as evidenced by: unstable angina, history of myocardial infarction within 6 months prior to Day 1, or cerebrovascular accident within 6 months prior to Day 1
  -  Active autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs or active inflammatory disease which requires immunosuppressive therapy
  -  Clinically significant history of liver disease
  -  History of adrenal insufficiency or hyperaldosteronism
  -  Phase II only: Previous therapy for prostate cancer with 17 alpha-hydroxylase/C17,20-lyase inhibitors, including abiraterone
  -  Phase II only: Previous treatment for prostate cancer with Protein kinase B phosphatidylinositol 3 kinase and/or mammalian target of rapamycin inhibitors
  -  Need for chronic corticosteroid therapy of >/= 20 mg of prednisone per day or an equivalent dose of other anti inflammatory corticosteroids or immunosuppressant

Relevance to patient case: not relevant
Patient case: 57-year-old male with melanoma; genetic feature: BRAF (V600E), PTEN loss of function

Clinical trial: cKIT, BRAF/NRAS Mutations in Advanced Melanoma : Clinical Outcome in Response to Tyrosine-kinase Inhibitors - KitMel Project

Summary: Background: Metastatic melanoma has a devastating prognosis and is one of the top causes of cancer death in young patients. Until now, available therapies were few and unreliable, but recent understanding of melanomas' molecular pathways has improve their classification and new clinical strategies have been proposed.
  Initial studies showed that B-Raf/N-Ras mutations (respectively V600E and Q61) are the most frequent alteration being present in 70 to 80% of melanomas, characterizing non Chronic Sun-induced Damage skins (CSD). These include Superficial Spreading Melanomas (SSM) and Nodular Melanomas (NM). Other studies showed that c-Kit mutations are presently the predominant activating mutation (20 - 40 %) in Acro-Lentiginous Melanomas (ALM), Mucous Melanomas (MM) and in melanomas arising on CSD skin. c-Kit mutation pattern is more complex with four exons being affected leading to different mutations, which incidence and biological impact are less documented.
  BRAF/NRAS genetics alterations drive constantly cell growth, being thus attractive targets. Spectacular results have indeed been obtained with the BRAF inhibitor that targets the V600E BRAF-mutated form. Data from GIST disease revealed that the different c-Kit mutations modulate differently c-Kit function and the response to targeted therapies.
  Because c-Kit targeted therapy is a critical clinical issue, the investigators aimed to identify the most frequent mutations present in our population to propose appropriate screening test and adapt the therapy.
  Methods: 250 melanoma samples corresponding to an homogeneous white-Caucasian population (Brittany, France) will be screened. c-Kit exons 11, 13, 17 and 18 will be sequenced (direct sequencing and pyrosequencing when possible). c-Kit copy number will be quantified by q-PCR and level of c-Kit determined by immunohistochemistry (IHC, CD117). Samples will also be analyzed for B-Raf mutations in codon 464, 466, 469 and 600, and for N-Ras mutations in codon 12, 13 and 61 (Pyrosequencing).
  Expected Results:
  Taken together, the investigators anticipate that the present genetic analysis of the tumours from patients with advanced melanoma will first document the type and frequency of cKit mutations, will confirm or not that BRAF, NRAS and cKit mutations are mutually exclusive and document their repartition in the melanomas sub-types. Finally this study will clue researchers in to how well patients will respond to a therapy that targets the growth-promoting proteins BRAF/NRAS and cKIT.


Eligibility: Inclusion Criteria:
  -  melanoma
  -  white caucasian population

Relevance to patient case: definitely relevant
Patient case: 57-year-old male with melanoma; genetic feature: BRAF (V600E), PTEN loss of function

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

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

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

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

Relevance to patient case: possibly relevant
Patient case: 57-year-old male with melanoma; genetic feature: BRAF (V600E), PTEN loss of function

Clinical trial: A Study Comparing Trametinib and Dabrafenib Combination Therapy to Dabrafenib Monotherapy in Subjects With BRAF-mutant Melanoma

Summary: This is a two-arm, double-blinded, randomized, Phase III study comparing dabrafenib (GSK2118436) and trametinib (GSK1120212) combination therapy to dabrafenib administered with a trametinib placebo (dabrafenib monotherapy). Subjects with histologically confirmed cutaneous melanoma that is either Stage IIIC (unresectable) or Stage IV, and BRAF V600E/K mutation positive will be screened for eligibility. Subjects who have had prior systemic anti-cancer treatment in the advanced or metastatic setting will not be eligible although prior systemic treatment in the adjuvant setting will be allowed. Approximately 340 subjects will be randomized 1:1 (combination therapy: dabrafenib monotherapy). Subjects will be stratified by lactate dehydrogenase (LDH) level (> the upper limit of normal (ULN) versus less than or equal to the ULN) and BRAF mutation (V600E versus V600K). The primary endpoint is investigator-assessed, progression-free survival for subjects receiving the combination therapy compared with those receiving dabrafenib monotherapy. Subjects will be followed for overall survival; crossover will not be permitted.


Eligibility: Inclusion Criteria:
  -  Histologically confirmed cutaneous melanoma that is either Stage IIIC (unresectable) or Stage IV (metastatic), and determined to be BRAF V600E/K mutation-positive using the bioMerieux (bMx) investigational use only (IUO) THxID BRAF Assay (IDE: G120011). The assay will be conducted by a central reference laboratory. Subjects with ocular or mucosal melanoma are not eligible.
  -  The subject must have a radiologically 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 counts
  Exclusion Criteria:
  -  Prior treatment with a BRAF or a MEK inhibitor
  -  Prior systemic anti-cancer treatment for Stage IIIC (unresectable) or Stage IV (metastatic) melanoma. Prior systemic treatment in the adjuvant setting is allowed. (Note: Ipilimumab treatment must end at least 8 weeks prior to randomization.)
  -  The subject has received major surgery or certain tyes of cancer therapy with 21 days of starting treatment
  -  Current use of prohibited medication listed in the protocol
  -  Left ventricular ejection fraction less than the lower limit of normal
  -  Uncontrolled blood pressurl
  -  History or current evidence of retinal vein occlusion or central serous retinopathy
  -  Brain metastases unless previously treated with surgery or stereotactic radiosurgery and the disease has been stable for at least 12 weeks
  -  The subject is pregnant or nursing

Relevance to patient case: definitely relevant
Patient case: 57-year-old male with melanoma; genetic feature: BRAF (V600E), PTEN loss of function

Clinical trial: Study Of Zelboraf (Vemurafenib) in Patients With Locally-Advanced, Unresectable, Stage IIIc Or Metastatic Melanoma and Activating Exon 15 BRAF Mutations Other Than V600E

Summary: This is an open-label, multicenter, single-agent, phase II study of continuous oral Zelboraf (vemurafenib) in patients with locally-advanced, unresectable, stage IIIc or metastatic melanoma and activating exon 15 BRAF mutations other than V600E.


Eligibility: Inclusion Criteria:
  -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
  -  Histologically-confirmed metastatic melanoma (unresectable Stage IIIc or IV) with an activating BRAF mutation other than V600E
  -  Measurable disease (as defined by RECIST, v1.1)
  -  Adequate recovery from most recent systemic or local treatment for cancer
  -  Adequate organ function
  -  Women of childbearing potential and male partners of women of childbearing potential: agreement to use prescribed contraception.
  -  Negative serum 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 vemurafenib; for male patients, agreement not to donate sperm during the study and for at least 6 months after discontinuation of vemurafenib
  Exclusion Criteria:
  -  Invasive malignancy other than melanoma at the time of enrollment and within 2 years prior
  -  Pregnant or breast-feeding
  -  Concurrent anti-tumor therapy (e.g., chemotherapy, other targeted therapy, radiation therapy, including participation in an experimental drug study)
  -  Either a concurrent condition or history of a prior condition that places the patient at unacceptable risk if he/she were treated with the study drug or confounds the ability to interpret data from the study
  -  Ongoing cardiac dysrhythmia >/= Grade 2

Relevance to patient case: possibly relevant
Patient case: 57-year-old male with melanoma; genetic feature: BRAF (V600E), PTEN loss of function

Clinical trial: Dabrafenib Plus Trametinib vs Vemurafenib Alone in Unresectable or Metastatic BRAF V600E/K Cutaneous Melanoma

Summary: This is a two-arm, open-label, randomised, Phase III study comparing dabrafenib (GSK2118436) and trametinib (GSK1120212) combination therapy to vemurafenib. Subjects with histologically confirmed cutaneous melanoma that is either stage IIIc (unresectable) or stage IV, and BRAF V600E/K mutation positive will be screened for eligibility. Subjects who have had prior systemic anti-cancer treatment in the advanced or metastatic setting will not be eligible although prior systemic treatment in the adjuvant setting will be allowed. Approximately 694 subjects will be randomised 1:1 (combination therapy:vemurafenib). The primary endpoint is overall survival (OS) for subjects receiving the combination therapy compared with those receiving vemurafenib.


Eligibility: Inclusion Criteria:
  -  >= 18 years of age
  -  Stage IIIc or Stage IV BRAF V600E/K cutaneous melanoma
  -  Measurable disease according to RECIST 1.1
  -  Women of childbearing potential with negative serum pregnancy test prior to randomisation
  -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  -  Adequate baseline organ function
  Exclusion Criteria:
  -  Any prior use of a BRAF or MEK inhibitor
  -  Prior systemic anti-cancer treatment in the advanced or metastatic setting; prior systemic treatment in the adjuvant setting is allowed
  -  History of another malignancy (except subjects who have been disease free for 3 years or with a history of completely resected non-melanoma skin cancer)
  -  Known HIV, HBV, HCV infection (except chronic or cleared HBV and HCV infection which will be allowed)
  -  Brain metastases (except if all known lesions were previously treated with surgery or stereotactic radiosurgery and lesions, if still present, are confirmed stable for >= 12 weeks prior to randomisation or if no longer present are confirmed no evidence of disease for >= 12 weeks, and are asymptomatic with no corticosteroid requirements for >= 4 weeks prior to randomisation, and no enzyme inducing anticonvulsants for >= 4 weeks prior to randomisation
  -  History or evidence of cardiovascular risk (LVEF < LLN; QTcB >= 480 msec; blood pressure or systolic >=140 mmHg or diastolic >= 90 mmHg which cannot be controlled by anti-hypertensive therapy)
  -  History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR)

Relevance to patient case: definitely relevant
Patient case: 57-year-old male with melanoma; genetic feature: BRAF (V600E), PTEN loss of function

Clinical trial: BRIM8: A Study of Vemurafenib Adjuvant Therapy in Patients With Resected Cutaneous BRAF Mutant Melanoma

Summary: This multicenter, randomized, double-blind, placebo-controlled study will evaluate the efficacy and safety of vemurafenib in participants with completely resected, cutaneous BRAF mutation-positive melanoma at high risk for recurrence. Participants will be randomized to receive oral doses of vemurafenib 960 milligrams (mg) twice daily or matching placebo. The anticipated time on study treatment is 52 weeks.


Eligibility: Inclusion Criteria:
  -  Histologically confirmed melanoma of cutaneous origin
  -  Surgically rendered free of disease within 90 days of randomization
  -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  -  Life expectancy of at least 5 years
  -  Fully recovered from the effects of any major surgery or significant traumatic injury prior to the first dose of study treatment
  -  Adequate hematologic, hepatic, and renal function
  Exclusion Criteria:
  -  History of any systemic or local therapy (e.g., chemotherapy, biologic or targeted therapy, hormonal therapy, or photodynamic therapy) for the treatment or prevention of melanoma, including interferon alpha-2b and pegylated interferon alpha-2b
  -  History of limb perfusion therapy
  -  History of radiotherapy for the treatment of melanoma
  -  Invasive malignancy other than melanoma at the time of enrollment or within 5 years prior to first dose of study treatment
  -  Family history of inherited colon cancer syndromes
  -  History of clinically significant cardiac or pulmonary dysfunction
  -  Major surgical procedure within 4 weeks prior to first dose of study treatment
  -  Infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C virus

Relevance to patient case: definitely relevant