araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 80-year-old male with melanoma; genetic feature: BRAF (V600R)

Clinical trial: A Phase I Study of Oral LGX818 in Adult Patients With Advanced or Metastatic BRAF Mutant Melanoma

Summary: CLGX818X2101 is a first-time in-human, phase I study to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of daily administered LGX818 (daily, twice daily and/or every-other-day), a RAF kinase inhibitor. Patients with locally advanced or metastatic melanoma harboring the BRAF V600 mutation (during dose escalation phase and expansion phase) and patients with metastatic colorectal cancer harboring the BRAF V600 mutation (during the expansion phase) will be enrolled. The study consists of a dose escalation part were cohorts of patients will receive escalating oral doses of LGX818, followed by a safety dose expansion part were patients will be treated with oral dose of LGX818 given at the MTD or RP2D.


Eligibility: Inclusion Criteria:
  For the dose escalation phase:
  1. Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage IIIB to IV per American Joint Committee on Cancer [AJCC]). For the dose expansion phase: (i) Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage IIIB to IV per American Joint Committee on Cancer [AJCC]), or (ii) confirmed diagnosis and non-resectable advanced metastatic colorectal cancer (mCRC) for which no further effective standard therapy exists.
  2. Written documentation of BRAF V600E mutation, or any other BRAF V600 mutation.
  3. Evidence of measurable disease
  Exclusion Criteria:
  1. Previous therapy with a MEK inhibitor.
  2. Symptomatic or untreated leptomeningeal disease.
  3. Symptomatic or untreated brain metastasis.Patients previously treated for these conditions that are asymptomatic in the absence of corticosteroid therapy are allowed to enroll. Brain metastasis must be stable with verification by imaging.
  4. Known acute or chronic pancreatitis.
  5. Clinically significant cardiac disease
  6. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LGX818
  7. Previous or concurrent malignancy. Exceptions to this exclusion criteria include: adequately treated basal cell or squamous cell skin cancer; in situ carcinoma of the cervix, treated curatively and without evidence of recurrence for at least 3 years prior to study entry; or other solid tumor treated curatively, and without evidence of recurrence for at least 3 years prior to study entry.
  8. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL).
  9. History of thromboembolic or cerebrovascular events within the last 6 months
  Other protocol-defined inclusion/exclusion criteria may apply

Relevance to patient case: definitely relevant
Patient case: 80-year-old male with melanoma; genetic feature: BRAF (V600R)

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: 80-year-old male with melanoma; genetic feature: BRAF (V600R)

Clinical trial: A Study of Zelboraf (Vemurafenib) in Patients With BRAF V600 Mutation-Positive Cancers

Summary: This open-label, multi-center study will assess the efficacy and safety of Zelboraf (vemurafenib) in patients with BRAF V600 mutation-positive cancers (solid tumors and multiple myeloma, except melanoma and papillary thyroid cancer) and for whom Zelboraf is deemed the best treatment option in the opinion of the investigator. Patients will receive twice daily oral doses of 960 mg Zelboraf until disease progression, unacceptable toxicity, or withdrawal of consent.
  The safety and efficacy of Zelboraf in combination with cetuximab in a subset of patients with colorectal cancer will also be assessed.


Eligibility: Inclusion Criteria:
  -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  -  Must have recovered from all side effects of their most recent systemic or local treatment
  -  Adequate hematological, renal and liver function
  For solid tumors only:
  -  Histologically confirmed cancers (excluding melanoma and papillary thyroid cancer) with a BRAF V600 mutation and that are resistant to standard therapy or for which standard or curative therapy does not exist
  -  Measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST)
  For multiple myeloma only:
  -  Confirmed diagnosis of multiple myeloma with a BRAF V600 mutation
  -  Patients must have received at least one prior systemic therapy for the treatment of multiple myeloma
  -  Patients treated with local radiotherapy
  -  Patients must have relapsed and/or refractory multiple myeloma with measurable disease
  Exclusion Criteria:
  -  Melanoma, papillary thyroid cancer or hematological malignancies (with the exception of multiple myeloma)
  -  Uncontrolled concurrent malignancy
  -  For patients with multiple myeloma: solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia
  -  Active or untreated CNS metastases
  -  History of or known carcinomatous meningitis
  -  Concurrent administration of any anti-cancer therapies other than those administered in this study
  -  Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that would, in the investigator's opinion, contraindicate participation in this study

Relevance to patient case: not relevant
Patient case: 80-year-old male with melanoma; genetic feature: BRAF (V600R)

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: possibly relevant
Patient case: 80-year-old male with melanoma; genetic feature: BRAF (V600R)

Clinical trial: A Study of MEK162 and AMG 479 in Patients With Selected Solid Tumors

Summary: This is a multi-center, open-label, phase Ib/II study. First, the aim of the phase Ib part is to estimate the MTD(s) and/or to identify the recommended phase II dose(s) (RP2D) for the combination of MEK162 and AMG 479 (ganitumab), followed by the phase II part to assess the clinical efficacy and to further assess the safety of the combination in selected patient populations. The dose escalation part of the study will be guided by a Bayesian Logistic Regression Model (BLRM). At least 18 patients are expected to be enrolled in the dose escalation part.
  Following MTD/ RP2D declaration, patients will be enrolled in three phase II arms to assess efficacy of the combination as well as to better understand the safety, tolerability, PK, antibody concentrations and PD of the combination at MTD/RP2D. Phase II arm 1 will consist of approximately 25 patients with KRAS-mutant colorectal adenocarcinoma. Phase II arm 2 will consist of approximately 20 patients with metastatic pancreatic adenocarcinoma. Phase II arm 3 will consist of approximately 28 patients with mutant BRAFV600 melanoma.
  Patients will be treated until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurs first. All patients will be followed up - at minimum patients must complete the safety follow-up assessments 30 days after the last dose of the study treatment.


Eligibility: Inclusion Criteria:
  -  Patients aged ≥ 18 years
  -  Patients with advanced solid tumors (CRC, melanoma) with documented somatic KRAS or BRAFV600 mutations in tumor tissue. Patients with metastatic pancreatic adenocarcinoma may be enrolled irrespectively of KRAS or BRAFV600 mutational status.
  -  Patients must have relapsed or progressed following standard therapy or patients for whom no standard anticancer therapy exists.
  -  Measurable disease as determined by RECIST v1.1. World Health Organization (WHO) Performance Status (PS) ≤ 2.
  -  Adequate organ function
  -  Negative serum pregnancy test
  Exclusion Criteria:
  -  Prior therapy with MEK- or IGF-1R- inhibitor
  -  History or current evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO) or retinal degenerative disease
  -  Patients with known history of severe infusion reactions to monoclonal antibodies
  -  Patients with primary CNS tumor or CNS tumor involvement
  -  History of thromboembolic event requiring full-dose anticoagulation therapy
  -  Clinically significant cardiac disease
  -  History of another malignancy within 2 years
  -  Pregnant or nursing (lactating) women
  Other protocol-defined inclusion/exclusion criteria may apply

Relevance to patient case: possibly relevant
Patient case: 80-year-old male with melanoma; genetic feature: BRAF (V600R)

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: possibly relevant
Patient case: 80-year-old male with melanoma; genetic feature: BRAF (V600R)

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: definitely relevant
Patient case: 80-year-old male with melanoma; genetic feature: BRAF (V600R)

Clinical trial: Autonomic Phenotype Before and After Akt Inhibition

Summary: Some Akt inhibitors have produced functional cardiovascular effects such as marked hypotension that may limit their clinical benefit. There are no current data on whether this autonomic failure presents in humans at clinically used doses. We will test the hypothesis that Akt inhibition causes an acute decrease in sympathetic tone and lowers blood pressure.


Eligibility: Inclusion Criteria:
  -  Diagnosed with melanoma with a BRAF mutation and relapse following therapy with a BRAF inhibitor
  -  Enrolled in a clinical trial through the Vanderbilt Ingram Cancer Center (VICC) including an arm with an oral Akt inhibitor
  -  Able and willing to provide informed consent
  Exclusion Criteria:
  -  Factors which in the investigator's opinion would prevent the participant from completing the protocol, including poor compliance during previous studies or an unpredictable schedule
  -  Unable to give informed consent

Relevance to patient case: possibly relevant
Patient case: 80-year-old male with melanoma; genetic feature: BRAF (V600R)

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: possibly relevant
Patient case: 80-year-old male with melanoma; genetic feature: BRAF (V600R)

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