araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 61-year-old male with melanoma; genetic feature: BRAF amplification

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

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


Eligibility: Inclusion Criteria:
  -  Must be at least 18 years of age
  -  Must have histologically confirmed cutaneous metastatic melanoma (Stage IV) that is BRAF mutation-positive (V600 E/K) as determined via central testing with a BRAF mutation assay.
  -  Is treatment naive or has received prior treatment for metastatic melanoma.
  -  Must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
  -  Women of child-bearing potential must have a negative pregnancy test within 14 days prior to the first dose of study treatment.
  -  Women with reproductive potential must be willing to practice acceptable methods of birth control during the study and for up to 4 weeks after the last dose of study medication.
  -  Men with reproductive potential must be willing to practice acceptable methods of birth control during the study and for up to 16 weeks after the last dose of study medication.
  -  Must have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
  -  Adequate organ function.
  Exclusion Criteria:
  -  Previous treatment with a BRAF or MEK inhibitor.
  -  Cancer therapy (chemotherapy with delayed toxicity, radiation therapy, immunotherapy, biologic therapy, or major surgery) within the last 3 weeks; chemotherapy regimens without delayed toxicity within the last 2 weeks; or use of any investigational anti-cancer or other drug within 28 days or 5 half-lives, whichever is longer, preceding the first dose of GSK2118436.
  -  A history of known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection.
  -  History or evidence of brain metastases on MRI or head CT if MRI is not able to be performed.
  -  History of other malignancy. Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
  -  Certain cardiac abnormalities.

Relevance to patient case: possibly relevant
Patient case: 61-year-old male with melanoma; genetic feature: BRAF amplification

Clinical trial: Early Diagnosis of Malignant Transformation of Pigmentary Skin Lesions

Summary: Malignant Melanoma is a deadly skin cancer that can be cured if diagnosed early. To date atypical pigmented skin lesions are diagnosed by appearance alone and many moles and lesions are excised unnecessarily and on the other hand malignant lesions are missed and diagnosed too late. In this study a protein conjugated to a florescent dye is spread on a suspicious pigmented lesion, the hypothesis is that this protein binds to malignant cells only and thus with a special camera that picks up the dye we can find pigmented lesions with early malignant transformation.


Eligibility: Inclusion Criteria:
  -  pigmented lesion indicated for surgical excision
  -  over 18 years of age
  Exclusion Criteria:
  -  pregnancy

Relevance to patient case: not relevant
Patient case: 61-year-old male with melanoma; genetic feature: BRAF amplification

Clinical trial: A Study of the Effect of Food on the Pharmacokinetics of Single Dose RO5185426 And the Safety And Efficacy of Continuous Administration in Patients With BRAF V600E Mutation-Positive Metastatic Melanoma

Summary: This randomized, open-label, two period crossover study will evaluate the effect of food on the pharmacokinetics of a single dose of RO5185426 and the efficacy and safety of continuous administration in patients with BRAF V600E mutation-positive metastatic melanoma. Patients will be randomized to receive in a crossover design single oral doses of RO5185426 with or without food, with a 10-day washout period between doses. Following the crossover periods, patients will receive RO5185426 orally twice daily on a continuous basis until disease progression or unacceptable toxicity occurs.


Eligibility: Inclusion Criteria:
  -  Adult patients, >/= 18 years of age
  -  Histologically confirmed metastatic melanoma (Stage IV, American Joint Committee on Cancer)
  -  Positive BRAF V600E mutation result determined by Cobas 4800 BRAF V600 Mutation Test
  -  Previously treated patients must have failed at least one prior treatment regimen; if patients have received prior systemic treatments for metastatic melanoma, the time elapsed from previous therapy must be >/= 28 days; patients must have recovered fully from toxicities of all prior therapy
  -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  -  Evaluable disease (measurable for disease progression according to RECIST criteria)
  -  Adequate hematological, renal and liver function
  Exclusion Criteria:
  -  Active CNS lesions
  -  History of or known spinal cord compression or carcinomatous meningitis
  -  Anticipated or ongoing administration of anti-cancer therapies other than those administered in this study
  -  Previous malignancy within the past 5 years except for basal or squamous cell carcinoma of the skin, melanoma in-situ and carcinoma in-situ of the cervix
  -  Previous treatment with BRAF inhibitor (sorafenib allowed) or MEK inhibitor
  -  Refractory nausea or vomiting, malabsorption, external biliary shunt, or history of any type of gastrointestinal surgery that would preclude adequate absorption of study drug

Relevance to patient case: possibly relevant
Patient case: 61-year-old male with melanoma; genetic feature: BRAF amplification

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

Summary: This open-label, multicenter study will evaluate the safety and efficacy of RO5185426 in patients with BRAF V600 mutation-positive, surgically incurable and unresectable stage IIIC or IV metastatic melanoma. Eligible patients will receive RO5185426 (960 mg twice daily orally) until disease progression or unacceptable toxicity occurs, with a safety follow-up of 24 months after discontinuation of the study drug.


Eligibility: Inclusion Criteria:
  -  Adult patients, >/= 16 years of age
  -  Histologically confirmed metastatic melanoma (surgically incurable and unresectable stage IIIC or stage IV; AJCC) with BRAF V600 mutation determined by Cobas 4800 BRAF Mutation Test
  -  Patients may or may not have received prior systemic therapy for metastatic melanoma
  -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  -  Adequate hematologic, renal and liver function
  Exclusion Criteria:
  -  Evidence of symptomatic CNS lesions, use of steroids or anti-seizure medications for treatment of brain metastases prior to the first administration of RO5185426
  -  Previous malignancy (other than melanoma) within the past 2 years, except for treated and controlled basal or squamous cell carcinoma of the skin or carcinoma in-situ of the cervix
  -  Concurrent administration of any anti-cancer therapies other than those administered in the study
  -  Clinically significant cardiovascular disease or event within the 6 months prior to first administration of study drug
  -  Refractory nausea or vomiting, external biliary shunt, or significant bowel resection that would preclude adequate absorption

Relevance to patient case: possibly relevant
Patient case: 61-year-old male with melanoma; genetic feature: BRAF amplification

Clinical trial: A Phase II Study of Single Agent MEK162 in Patients With Advanced Melanoma

Summary: The study will assess the safety and efficacy of single-agent MEK162 in adult patients with locally advanced and unresectable or metastatic malignant cutaneous melanoma, harboring BRAFV600E or NRAS mutations.


Eligibility: Inclusion Criteria:
  -  Locally advanced or metastatic cutaneous melanoma AJCC Stage IIIB to IV, not potentially curable with surgery
  -  BRAF or NRAS mutation in tumor tissue
  -  All patients enrolled should provide sufficient fresh or archival tumor sample at baseline to enable confirmation of BRAF or NRAS mutations and the additional analyses described in the protocol
  -  Evidence of measurable tumor disease as per RECIST
  -  WHO performance status of 0-2
  -  Adequate organ function and laboratory parameters
  Exclusion Criteria:
  -  History or evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO) or any eye condition that would be considered a risk factor for CSR or RVO
  -  Patients with unstable CNS metastasis
  -  Prior treatment with a MEK- inhibitor
  -  Impaired cardiovascular function
  -  HIV, active Hepatitis B, and/or active Hepatitis C infection
  -  Pregnant or nursing (lactating) women
  -  Women of child-bearing potential UNLESS they comply with protocol contraceptive requirements
  Other protocol-defined inclusion/exclusion criteria may apply.

Relevance to patient case: possibly relevant
Patient case: 61-year-old male with melanoma; genetic feature: BRAF amplification

Clinical trial: Detection of Choroidal Nevus Cells in Vitrectomy Fluid

Summary: The purpose of this study is to determine if the investigators can detect the presence of choroidal nevi cells in the vitreous fluid of humans, as this may improve the diagnosis and classification of choroidal nevi and melanomas in the future.

Detailed description: Approximately 7% of the population has a choroidal nevus, or "freckle," in the back of the eye. Like a nevus on the skin, there is potential for malignant change to a melanoma. Dermatologists have the ability to quickly and easily biopsy suspicious skin lesions while ophthalmologists currently have no way of determining the malignant potential of choroidal nevi other than a fine needle aspiration (which is invasive and has the potential complications of bleeding and retinal detachment). This study's sole aim is to see if choroidal nevi cells are present in the inside fluid of the eye. The investigators plan to analyze the fluid of the eye, which is routinely removed during retina surgery, to detect any nevus cells. If the investigators are able to detect these cells, then future studies may allow us to better classify choroidal nevi for potential malignant change.

Eligibility: Inclusion Criteria:
  -  Patients with a choroidal nevus who are undergoing routine vitrectomy surgery for another indication (such as epiretinal membrane or macular hole repair).
  Exclusion Criteria:
  -  Patients without a choroidal nevus
  -  Children under the age of 18
  -  Pregnant and nursing females

Relevance to patient case: not relevant
Patient case: 61-year-old male with melanoma; genetic feature: BRAF amplification

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

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


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

Relevance to patient case: not relevant
Patient case: 61-year-old male with melanoma; genetic feature: BRAF amplification

Clinical trial: Ph I Ipilimumab Vemurafenib Combo in Patients With v-Raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF)

Summary: Treatment of subjects who have metastatic melanoma that expresses an activated mutant form of the BRAF oncogene (V600E) with a combination of the specific BRAF inhibitor, Vemurafenib, and the Cytotoxic T Lymphocyte Antigen 4 (CTLA-4) inhibitor mAb Ipilimumab will be safe and feasible and will show preliminary evidence of anti-tumor efficacy and survival in comparison to historical results following treatment with either agent alone.


Eligibility: For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.
  Inclusion Criteria:
  -  Metastatic melanoma with activating V600 BRAF mutation
  -  Measurable Tumor
  -  Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1
  Exclusion Criteria:
  -  Autoimmune disease
  -  Active Brain Metastasis (must be stable after radiation for at least one month)
  -  Prior therapy with immune stimulating agents

Relevance to patient case: possibly relevant
Patient case: 61-year-old male with melanoma; genetic feature: BRAF amplification

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: possibly relevant
Patient case: 61-year-old male with melanoma; genetic feature: BRAF amplification

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: not relevant
Patient case: 61-year-old male with melanoma; genetic feature: BRAF amplification

Clinical trial: Study of Circulating Tumor Cells Before and After Treatment in Patients With Metastatic Melanoma

Summary: Circulating tumor cells (CTC) are the subject of increasing interest in clinical oncology as a prognostic factor and predictor of therapeutic response. The detection of CTC by immunomagnetic method has proved its reliability and its usefulness for monitoring breast cancer, colon and prostate in the metastatic and immunomagnetic detection system (CellSearch, Veridex LLC) was approved by the FDA in these indications. However, to date there is no reliable method to detect CTCs in melanoma (CMC). Studies based on PCR amplification of mRNA by reverse specific melanoma is disappointing. Recently, a new detection system of CMC immunomagnetic was presented (CellSearch, Veridex LLC, United States). This system has the advantage of combining immunomagnetic selection step and a step of identifying by immunofluorescence. A preclinical study on serial dilutions of melanoma cells has shown encouraging results. The investigators propose a prospective study of the CellSearch system in patients with melanoma.
  Primary objective: To determine the effect of treatment on the number of circulating melanoma cells in patients with metastatic melanoma.
  Secondary objectives:
  -  determine the percentage of patients with metastatic melanoma with melanoma cells circulating
  -  seek a relationship between the number of circulating melanoma cells and prognosis in patients with metastatic melanoma
  -  seek a relationship between the change in the number of circulating melanoma cells before / after treatment and tumor response in patients with metastatic melanoma


Eligibility: Inclusion Criteria:
  -  Patients > or = 18 years
  -  Patients with advanced melanoma stage IIIC (unresectable) or stage IV
  -  Patient not treated or not responding to chemotherapy with chemotherapy session last> 1 month
  -  Patients who signed informed consent
  -  Patients presenting no socio-economic, psychological, familial or geographical allow proper understanding of the information leaflet of the protocol or the regular monitoring in the department of dermatology
  -  Patients with a life expectancy greater than 3 months
  -  Patients with melanoma measurable by RECIST version 1.1
  -  Patients with venous good for venipuncture
  Exclusion Criteria:
  -  Patients with contraindication for treatment with chemotherapy or V600E BRAF inhibitor or ipilimumab or have conditions concomitant heavy may interfere with the treatment of metastatic melanoma
  -  Pregnant women or nursing
  -  People vulnerable detainees, adults under guardianship or curatorship, minors.

Relevance to patient case: not relevant