araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 32-year-old male with melanoma; genetic feature: NRAS (Q61H)

Clinical trial: Studying Tumor Tissue Samples From Patients With Melanoma Who Have Undergone Sentinel Lymph Node Biopsy

Summary: RATIONALE: Studying samples of tumor tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. It may also help the study of cancer in the future.
  PURPOSE: This laboratory study is looking at tumor tissue samples from patients with melanoma who have undergone sentinel lymph node biopsy.

Detailed description: OBJECTIVES:
  -  Develop a predictive model for sentinel lymph node biopsy positivity in patients with melanoma who have undergone sentinel lymph node biopsy.
  -  Develop a survival model for relapse based on sentinel lymph node biopsy positivity.
  -  Assess the genetic determinants in primary melanomas that predict a metastatic phenotype and thereby improve understanding of the biology of the metastases in melanoma.
  OUTLINE: This is a retrospective, case-controlled, multicenter study. Patients are stratified according to Breslow thickness of the tumor (0.75-1.50 mm vs 1.51- 4 mm vs > 4 mm) and gender.
  Archived tumor tissue is analyzed by immunohistochemistry (IHC) for AP2, vascular endothelial growth factor, MMP 2, MCM4, and others, if feasible. Sentinel node biopsies are analyzed by IHC for CD31, LYVE-1, and D2-40 expression. RNA and DNA are also extracted for genetic expression studies and mutation analysis (e.g., BRAF, NRAS, PTEN, CDKN2A).
  Patient data related to relapse and recurrence is collected, if available.
  Peer reviewed and funded or endorsed by Cancer Research UK
  PROJECTED ACCRUAL: A total of 1,000 patients will be accrued for this study.

Eligibility: DISEASE CHARACTERISTICS:
  -  Confirmed diagnosis of cutaneous melanoma
  -  Breslow thickness > 0.75 mm
  -  Has undergone sentinel lymph node biopsy
  -  No primary melanoma that has not originated in the skin
  -  No multiple primary melanomas
  -  Currently under clinical followup OR discharged from follow up within the past 3 months
  PATIENT CHARACTERISTICS:
  -  No other malignancy except for nonmelanoma skin cancer or cervical carcinoma in situ
  PRIOR CONCURRENT THERAPY:
  -  See Disease Characteristics

Relevance to patient case: definitely relevant
Patient case: 32-year-old male with melanoma; genetic feature: NRAS (Q61H)

Clinical trial: Genetic Identification (ID) of Segmental Dysplastic Nevi

Summary: The investigators' goal is to identify the mutation in the gene that is responsible for the development of segmental dysplastic nevi. To identify the gene the investigators may use a candidate gene approach (i.e. sequence specific genes that are thought to be involved: NRAS, BRAF, etc) or a genome-wide approach trying to implicate regions in the genome (Loss-of-heterozygosity or copy number changes on comparative genomic hybridization).

Detailed description: Dysplastic (atypical) melanocytic (DMN) nevi have been identified as being potential precursors of melanoma and markers for patients at risk of developing primary melanoma1. In addition, having an increased number of nevi is associated with increased risk1. DMN are present in 2-5% of white adults in the U.S. population and international studies have documented up to 18% prevalence2. These lesions may be present in at least 17% of white adults with melanoma and 20-50% of melanomas may arise in nevi and atypical nevi2. The exact gene(s) involved in the development of nevi have yet to be elucidated.
  Segmental dysplastic nevi are nevi that are restricted to one area of the body3. This condition is much rarer than the occurrence of dysplastic nevi, but nonetheless, may involve the same genetic mutation. The pattern of distribution in SDN is thought to result from mosaicism, i.e. the part of the body that expresses the dysplastic nevi has a mutation in a gene, however, the rest of the body does not contain this same mutation. Other mosaic disorders that have been studied in greater detail than SDN have been shown to be caused by a single gene mutation4. It appears that SDN is no different and that it too is caused by a mutation in a single gene, however, this gene is not yet known.
  In this study we will perform a genetic analysis of tissue from a patient known to have SDN. With the information we gather from this analysis, we may be able to find the gene responsible for the development of dysplastic nevi.
  Primary Research Objective:
  To investigate the genetic mutation involved in the development of dysplastic nevi by examining a patient with SDN.

Eligibility: Inclusion Criteria:
  -  Patient with a positive history of segmental dysplastic nevi
  Exclusion Criteria:
  -  None

Relevance to patient case: not relevant
Patient case: 32-year-old male with melanoma; genetic feature: NRAS (Q61H)

Clinical trial: Study of Tumor Tissue Samples From Patients With Stage I, Stage II, or Stage III Malignant Melanoma

Summary: RATIONALE: Studying the genes expressed in samples of tumor tissue from patients with cancer may help doctors identify biomarkers related to cancer.
  PURPOSE: This research study is looking at tumor tissue samples from patients with stage I, stage II, or stage III malignant melanoma.

Detailed description: OBJECTIVES:
  -  Determine the genetic profile of primary melanomas with and without synchronous regional nodal involvement by examining for 1) activating mutations B-Raf and N-Ras associated with melanoma development, and 2) allelic imbalances across the genome.
  -  Compare the genetic profile of primary melanomas from patients with and without lymph node involvement.
  -  Determine the combinations of genetic lesions that correlate with nodal metastasis by adopting a statistical machine learning approach to build a lesion-based classifier for nodal metastasis.
  OUTLINE: Laser capture microdissection is performed on the archived tissue samples to isolate melanoma cells. DNA is then purified from the samples and amplified using PCR. Matrix-assisted laser desorption/ionization (MALDI)-time of flight mass spectrometry technology is used to detect mutations of B-Raf and N-Ras. Single nucleotide polymorphism arrays are also performed.
  Information about the patient's demographics (e.g., TNM staging, sex, age, and tissue collection dates) will be gathered by chart review or from the Multidisciplinary Melanoma Conference at University Hospitals tumor conference report in order to match cases.

Eligibility: Inclusion Criteria:
  -  Node positive Group (experimental group)
  -  Primary melanoma > 2 mm in depth
  -  Metastasis must be > 0.1 mm and detectable by IHC or hematoxylin and eosin (H&E) to be considered node positive
  -  Slides and block for primary and node must be archived in UH dermatopathology
  -  Node Negative Group (control group)
  -  Primary melanoma > 2 mm in depth
  -  A negative sentinel lymph node must be negative by IHC and H&E
  -  No stage IV disease
  -  No acral and mucosal histology
  -  No history of prior invasive melanoma
  -  Underwent primary excision and sentinel lymph node biopsy within 3 months of each other
  -  Archived tissue available
  -  Slides and block for primary tumor and node biopsy must be archived in University Hospitals Case Medical Center (UH) dermatopathology
  Exclusion Criteria:
  -  Acral and mucosal histology
  -  Previous diagnosis of invasive melanoma
  -  previous chemotherapy or immunotherapy
  -  patients who are found to have stage IV disease during workup

Relevance to patient case: not relevant
Patient case: 32-year-old male with melanoma; genetic feature: NRAS (Q61H)

Clinical trial: Ultraviolet Light Exposure and Immunosuppression in Cutaneous Melanoma

Summary: This project seeks to understand differences in the serum vitamin D levels and immune status in cutaneous malignant melanoma patients with different UV exposure histories in New Mexico.

Detailed description: It is well established that ultraviolet radiation (UV) exposure is related to the development of melanoma. There is also evidence that immune reactions are altered after UV exposure in the skin (locally) and perhaps throughout the body (systemically). Additionally, while the role of vitamin D and melanoma development has not been fully established, UV-B exposure is essential for vitamin D production in the skin. Increased sun exposure is also related to the presence of solar elastosis, which might protect (1) or improve survival from melanoma. Thus, melanoma represents a unique model for studying UV exposure, the immune system, and vitamin D. Malignant melanoma is an antigenic cancer; therefore, the role of UV exposure-induced immunosuppression and vitamin D production in the recognition, destruction and growth inhibition of cancerous melanocytes is worth further study.
  To underscore the importance of this project, the Scientific Advisory Committee of the Melanoma Research Foundation and the Steering Committee of the Society of Melanoma Research have indicated a need to collect more human data on the host immune response mechanisms in melanoma and also to focus on the skin as a whole microenvironment, moving away from only in vitro experiments.

Eligibility: Inclusion Criteria:
  -  Resident of New Mexico
  -  Age between the 1 and 95
  -  Newly diagnosed with cutaneous invasive melanoma; any stage permitted (ICDO C44.0-9) between September 1, 2008 and December 31, 2011.
  -  SSM (superficial spreading melanoma) and NM (nodular melanoma) histological subtypes are allowed
  -  Access to a telephone or be able to participate in a personal interview at the clinic
  -  Physically and mentally competent to complete a 1-hour telephone or personal interview
  Exclusion Criteria:
  -  Ocular melanoma, LMM (lentigo maligna melanoma) or ALM (acral lentigo melanoma), and mucosal melanoma cases.
  -  No access to a telephone or is not able to meet with the interviewer.

Relevance to patient case: not relevant
Patient case: 32-year-old male with melanoma; genetic feature: NRAS (Q61H)

Clinical trial: A Pharmacokinetic Study of RO5185426 in Combination With a Drug Cocktail in Patients With Metastatic Melanoma

Summary: This open-label single-arm study will evaluate the effect of RO5185426 [RG7204; PLEXXIKON: PLX4032] on the pharmacokinetics of five CYP450 substrates (caffeine, warfarin + vitamin K, omeprazole, dextromethorphan, midazolam) administered as a drug cocktail to patients with metastatic melanoma. The study will also evaluate efficacy and safety of RO5185426. On day 1, patients will receive the drug cocktail. On days 6 to 19, patients will receive RO5185426 twice daily. On day 20, patients will receive RO5185426 and the drug cocktail and on days 21 to 25, patients will receive RO5185426. Assessments will be made at regular intervals during the dosing periods and at follow-up. Patients may continue on study treatment (RO5185426) until the development of progressive disease or unacceptable toxicity. Target sample size <50.


Eligibility: Inclusion Criteria:
  -  Adult patient >/= 18 years of age
  -  Malignant melanoma (Stage IV, AJCC)
  -  Patients who are treatment-naive or have received prior systemic treatments for metastatic melanoma. Time elapsed between previous treatment for metastatic disease and first administration of study drug must be at least 28 days
  -  Positive tested for BRAF mutation
  -  Patients must not be poor metabolizers of CYP450 enzymes 2C9, 2C19, or 2D6 as determined by genotyping
  -  Measurable disease by RECIST criteria
  -  Negative pregnancy test; for fertile men and women, effective contraception during treatment and for 6 months after completion
  Exclusion Criteria:
  -  Active CNS lesions on CT/MRI within 28 days prior to enrollment
  -  History of known spinal cord compression, or carcinomatous meningitis
  -  Severe cardiovascular disease within 6 months prior to study

Relevance to patient case: not relevant
Patient case: 32-year-old male with melanoma; genetic feature: NRAS (Q61H)

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

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


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

Relevance to patient case: not relevant
Patient case: 32-year-old male with melanoma; genetic feature: NRAS (Q61H)

Clinical trial: Pemetrexed and Gemcitabine for Treatment Resistant Patients With Metastatic Colorectal Cancer and KRAS Mutations

Summary: This study aims to investigate the efficacy and safety of the combination of pemetrexed and gemcitabine in heavily pre-treated, chemotherapy resistant colorectal cancer patients with KRAS mutations.


Eligibility: Inclusion Criteria:
  -  Histologically verified adenocarcinoma in colon or rectum
  -  Age >18
  -  Metastatic colorectal cancer progressed after chemotherapy regimens containing fluoropyrimidines, oxaliplatin and irinotecan.
  -  KRAS mutation in primary tumour or metastasis.
  -  Measurable disease according to RECIST
  -  ECOG performance status 0, 1 or 2
  -  Adequate function of liver, kidneys and bone marrow measured by biochemistry (max. 2 weeks before enrolment)
  -  EDTA clearance: Uncorrected GFR > 45 ml/min.
  -  Neutrophilocytes ≥1.5 x 10^9/l, leukocytes ≥3.0 x 10^9/l, thrombocytes ≥100x10^9/l
  -  ALAT ≤ 3 x upper normal value (ULN), bilirubin ≤ 3 x upper normal value, Aptt and INR normal (or 2-3 at AC treatment). (ALAT and basic phosphatase ≤ 5 x upper normal value in case of liver metastases).
  -  Blood samples and paraffin embedded tissue from primary tumour and/or metastases for translational research.
  -  Fertile men and women (women <2 year after last menstruation) must use efficient birth control.
  -  Signed informed consent.
  Exclusion Criteria:
  -  Clinically significant other concurrent disease making the patient unfit for participation in the study according to the investigator.
  -  Other malignant disease within 5 years prior to study enrolment, except from planocellular and basal cell carcinomas in the skin or carcinoma-in-situ cervix.
  -  Other experimental treatment within 30 days prior to treatment start.
  -  Pregnant or breastfeeding women.
  -  Clinical or radiological signs of CNS metastases.
  -  Planned radiation of target lesions.
  -  Concurrent vaccination against yellow fever.

Relevance to patient case: not relevant
Patient case: 32-year-old male with melanoma; genetic feature: NRAS (Q61H)

Clinical trial: A Pharmacokinetic and Metabolism Study of 14C-labeled RO5185426 on Patients With Metastatic Melanoma

Summary: This open-label, non-randomized study will assess the mass balance, metabolism, routes and rates of elimination as well as efficacy and safety of RO5185426 (RG7204; PLEXXIKON; PLX4032) in previously treated or untreated patients with metastatic melanoma. Patients will receive continuous twice daily oral treatment with RO5185426. On Day 15, a 14C-labeled dose will be administered. Anticipated time on study treatment is until disease progression occurs.


Eligibility: Inclusion Criteria:
  -  Adult patients, >/= 18 years of age
  -  Histologically confirmed metastatic melanoma, surgically incurable and unresectable Stage IIIc or IV (AJCC)
  -  Prior treatment for metastatic melanoma allowed; >/= 28 days must be elapsed since previous systemic treatment prior to first administration of study drug
  -  Positive BRAF V600E mutation result (by Roche CoDx test)
  -  ECOG performance status 0-1
  -  Adequate hematologic, renal and liver function
  -  Body Mass Index (BMI) 18 to 32 kg/m2 inclusive
  Exclusion Criteria:
  -  Active CNS lesions
  -  History of or known spinal cord compression, or carcinomatous meningitis
  -  Anticipated or ongoing administration of any anticancer therapies other than those administered in this study
  -  Refractory nausea or vomiting, or other medical conditions that are capable of altering the absorption, metabolism or elimination of the study drug
  -  Known clinically significant active infection
  -  Known HIV positivity or AIDS-related illness, active HBV, or active HCV
  -  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
  -  Clinically significant cardiovascular disease or incident within the 6 months prior to study drug administration
  -  Patients who have had at least one dose of study drug (RO5185426 or comparator) in a clinical trial that includes RO5185426

Relevance to patient case: not relevant
Patient case: 32-year-old male with melanoma; genetic feature: NRAS (Q61H)

Clinical trial: Safety and Efficacy Study of BMS-908662 in Combination With Ipilimumab in Subjects With Advanced Melanoma

Summary: The purpose of the study is to identify a safe and tolerable dose of BMS-908662 in combination with ipilimumab; and then to evaluate the anti-tumor response to BMS-908662 when administered in combination with ipilimumab.


Eligibility: Inclusion:
  -  Male and female subjects ≥ 18 years of age with a histologic or cytologic diagnosis of Stage III or Stage IV (unresectable) melanoma
  -  Enrollment to cohort expansion will be limited to only those subjects whose tumors demonstrate the B-Raf V600E mutation
  -  ECOG ≤ 1
  -  Adequate organ & marrow function
  Exclusion:
  -  Uncontrolled or significant cardiovascular disease
  -  Cohort expansion: Prior therapy with a RAF inhibitor

Relevance to patient case: not relevant
Patient case: 32-year-old male with melanoma; genetic feature: NRAS (Q61H)

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: not relevant
Patient case: 32-year-old male with melanoma; genetic feature: NRAS (Q61H)

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: definitely relevant