araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 72-year-old male with melanoma; genetic feature: TP53 loss of function

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: not relevant
Patient case: 72-year-old male with melanoma; genetic feature: TP53 loss of function

Clinical trial: Physical and Cognitive Function - Look AHEAD Ancillary Study

Summary: Obesity is associated with physical disability through both direct pathways (e.g., lower extremity pain, insufficient muscle strength) and indirect pathways (obesity-related comorbidities and inflammation). Furthermore, diabetes, a major obesity-related health condition, is associated with increased risk of disability and accelerated declines in physical and cognitive function. The investigators preliminary data suggest that intentional weight loss improves physical function, and there is strong circumstantial evidence that it would also benefit cognitive function.
  To evaluate the role of intentional weight loss on physical and cognitive function, the investigators propose an ancillary study to the on-going Look AHEAD (Action for Health in Diabetes) trial. Look AHEAD is a multi-center, randomized clinical trial to examine the effects of a 4-year lifestyle intervention designed to achieve and maintain weight loss through decreased caloric intake and exercise in overweight or obese men and women aged 45-74 years with type 2 diabetes. The investigators propose to add validated and well-established measures of physical and cognitive performance to the year 8 follow-up visit - during the trial's weight maintenance phase - in ~1000 participants at 4 of the 16 Look AHEAD field sites (Colorado, Memphis, Pennington and Pittsburgh).
  The specific aims of this ancillary study are: 1) To determine the long-term effects of a lifestyle intervention designed to achieve and maintain weight loss on physical function; and 2) To determine the long-term effects of a lifestyle intervention designed to achieve and maintain weight loss on cognitive function. In addition, the investigators hypothesize that in the intervention group, larger initial weight loss, better weight loss maintenance, and higher physical activity will be associated with better physical and cognitive function. The investigators also hypothesize that in the control group weight loss will be associated with worse physical and cognitive function than in those who are weight stable or who have gained weight.
  The number of obese older adults is rising rapidly and there are few data to guide an evidence-based clinical response to their management. The results of this study will provide the first direct evidence of the role of long-term intentional weight loss on the maintenance of physical and cognitive function in older obese adults with diabetes. Since this study is being done as an ancillary study to an on-going trial it can be done in a timely and cost-efficient manner.


Eligibility: Inclusion Criteria:
  -  The only inclusion criterion is that the participant is considered "active" at his/her Year 8 or Year 9 visit in the main study.
  Exclusion Criteria:
  -  The only exclusion criterion is the person is not willing to participate in this ancillary study.

Relevance to patient case: not relevant
Patient case: 72-year-old male with melanoma; genetic feature: TP53 loss of function

Clinical trial: Safety Study of a Melanoma Vaccine (GVAX) With or Without Cyclophosphamide in Patients With Surgically Resected Melanoma

Summary: The primary objective of this study is to evaluate the safety and feasibility of administering an allogeneic GM-CSF-secreting lethally irradiated whole melanoma cell vaccine ("melanoma GVAX"), alone or in combination with low dose cyclophosphamide (CPM), for the adjuvant treatment of patients with surgically resected stage IIB-IV melanoma. Secondarily, the investigators will assess in vitro correlates of anti-melanoma immunization by melanoma GVAX, including serological and cellular immune responses in patients treated with either the vaccine alone or the vaccine given with low dose CPM.


Eligibility: Inclusion Criteria:
  -  Any patient age ≥18 years with melanoma of cutaneous or mucosal origin, and with clinicopathologic stage IIB, IIC, III or IV that has been completely resected
  -  Patients must be able to provide informed consent.
  -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  -  Life expectancy of at least 6 months.
  -  Adequate hematologic function.
  -  Adequate renal function
  -  Adequate hepatic function
  -  Patients of both genders must agree to practice effective birth control during the study period and for at least 4 weeks after the last treatment.
  Exclusion Criteria:
  -  Patients whose primary site of melanoma is ocular.
  -  Are undergoing or have undergone in the past 4 weeks any systemic treatment for melanoma.
  -  Are undergoing or have undergone in the past 2 weeks any surgery or focal radiation therapy.
  -  Have active systemic infections, coagulation disorders (including therapeutic anticoagulation), or other major medical or psychiatric illnesses.
  -  Are known to be positive for hepatitis B surface antigen, anti-Hepatitis C Virus or anti-Human Immunodeficiency Virus (HIV) antibody (because of possible immune effects of these conditions).
  -  Documented history of autoimmune disease, for example, systemic lupus erythematosus, sarcoidosis, rheumatoid arthritis, glomerulonephritis, or vasculitis.
  -  Any form of primary or secondary immunodeficiency. This would include hereditary disorders such as ataxia-telangiectasia or Wiskott-Aldrich syndrome, or acquired immune deficiencies such as following bone marrow transplantation.
  -  Requirement for systemic steroid therapy or immunosuppressive therapy.
  -  Have received any type of cancer immunotherapy, including but not limited to interleukin-2, interferon alfa or melanoma vaccines.
  -  Have been diagnosed with another invasive cancer within the past 3 years.
  -  Radiographic evidence of melanoma recurrence.
  -  Pregnant or lactating women.
  -  Known or suspected hypersensitivity to GM-CSF, pentastarch, hetastarch, corn, Dimethyl sulfoxide, fetal bovine serum or trypsin (porcine origin).

Relevance to patient case: not relevant
Patient case: 72-year-old male with melanoma; genetic feature: TP53 loss of function

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: not relevant
Patient case: 72-year-old male with melanoma; genetic feature: TP53 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: 72-year-old male with melanoma; genetic feature: TP53 loss of function

Clinical trial: Study of Safety and Pharmacokinetics of MK-8242 in Participants With Advanced Solid Tumors (P07650)

Summary: This study is being done to evaluate the safety and pharmacokinetic profile of MK-8242 and its active metabolite (M16) in participants with advanced solid tumors. In Part 1 of the study, the study drug dose will be escalated to determine the maximum tolerated dose (MTD). In Part 2 of the study, the MTD will be confirmed and the recommended Phase 2 dose (RPTD) established; the effect of MK-8242 on liposarcoma and other tumor types will also be evaluated.

Detailed description: Participants are considered to have completed the study after Cycle 12. Amendment 4 (14 April 2015) was done to allow participants on active treatment at the time the study was closed to enrollment to continue study treatment beyond Cycle 12 if deriving clinical benefit, at the Investigator's discretion.

Eligibility: Inclusion criteria:
  -  Histologically confirmed advanced solid tumor for which there are no effective standard therapy options
  -  Willing to provide tumor tissue for p53 wild type gene analysis
  -  Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
  -  Adequate organ function
  -  Female participants and male participants and their partners who are of childbearing potential must agree to abstain from sexual intercourse or to use an acceptable method of contraception during the study and for 90 days following the last dose of study drug
  -  At least one measurable lesion
  -  In Part 2, participants with liposarcoma must have a confirmed well-differentiated or de-differentiated histology
  Exclusion criteria:
  -  Known treated or untreated leptomeningeal metastases, or metastatic central nervous system disease
  -  History of recent myocardial infarction (within the past year); or with unstable or uncontrolled angina, New York Heart Association (NYHA) Class III or IV congestive heart failure, uncontrolled hypertension, clinically significant cardiac dysrhythmia or clinically significant electrocardiogram (ECG) abnormality
  -  Uncontrolled active infection on optimal systemic treatment
  -  Clinically significant hepatitis or hepatitis C antibody positive, hepatitis B surface antigen positive, or human immunodeficiency virus (HIV) seropositive
  -  Persistent, unresolved common terminology criteria for adverse events (CTCAE v4.0) ≥Grade 2 drug-related toxicity associated with previous treatment except for alopecia
  -  Radiation therapy or other loco-regional therapy within 2 weeks prior to study
  -  Use of moderate and strong cytochrome P450 inhibitors or inducers within 1 week prior to study
  -  Chemotherapy or any investigational drug(s) within 4 weeks prior to study
  -  Known hypersensitivity to MK-8242 or its components
  -  Nursing, pregnant, or intention to become pregnant during the study
  -  Initiating bisphosphonate therapy or adjusting the bisphosphonate dose or regimen within 30 days of Cycle 1 Day 1

Relevance to patient case: possibly relevant
Patient case: 72-year-old male with melanoma; genetic feature: TP53 loss of function

Clinical trial: Safety Study of IL-21/Ipilimumab Combination in the Treatment of Melanoma

Summary: The purpose of this study is to determine whether the combination of interleukin-21 (IL-21) and Ipilimumab in subjects with melanoma is safe, and provide preliminary information on the clinical benefits of the combination compared with Ipilimumab alone

Detailed description: Allocation: Part 1 Dose Escalation Phase: Non-randomized; Part 2 Cohort Expansion Phase: Randomized

Eligibility: For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.
  Inclusion Criteria:
  -  Unresectable Stage III or Stage IV melanoma
  -  Part 1 Dose Escalation: Prior melanoma treatment allowed except for the following: ipilimumab, BMS-982470 (rIL-21), anti-Programmed Death-1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), anti-PD-L2 or anti-CD137
  -  Part 2 Cohort expansion: Prior treatment for melanoma is not allowed, except for adjuvant therapy with interferon alpha or melanoma vaccines which are permitted
  -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  -  Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI)
  -  Normal liver function tests
  Exclusion Criteria:
  -  Part 1 Dose escalation: subjects with ≤ 2 brain metastases of stable size, ≥ 4 weeks post-radiation treatment, and off steroids are allowed
  -  Part 2 Cohort expansion: subjects with known or suspected brain metastases and uveal melanoma are excluded
  -  Autoimmune disease

Relevance to patient case: not relevant
Patient case: 72-year-old male with melanoma; genetic feature: TP53 loss of function

Clinical trial: Tissue and Blood Biomarkers From Patients With Stage III or Stage IV Melanoma Treated With Ipilimumab With or Without Sargramostim

Summary: RATIONALE: Studying samples of tissue and blood in the laboratory from patients treated with ipilimumab with or without sargramostim may help doctors learn more about the effects of ipilimumab and sargramostim on cells. It may also help doctors understand how well patients respond to treatment.
  PURPOSE: This research trial studies tissue and blood biomarkers in patients with stage III melanoma or stage IV melanoma treated with ipilimumab with or without sargramostim.

Detailed description: OBJECTIVES:
  -  To compare the pathology of primary melanomas, melanoma metastases, and post-treatment melanoma metastases in relation to clinical outcomes for patients receiving ipilimumab plus sargramostim (GM-CSF) and patients receiving ipilimumab alone.
  -  To determine the effects of the addition of systemic GM-CSF to ipilimumab on effector immune function in patients with metastatic melanoma.
  -  To determine the effects of the addition of systemic GM-CSF to ipilimumab on regulatory immune function in patients with metastatic melanoma.
  -  To determine the effects of the addition of systemic GM-CSF to ipilimumab on anti-tumor humoral immunity in patients with metastatic melanoma.
  OUTLINE: Serum, peripheral blood mononuclear cells, and tumor tissue (from primary tumor and post-treatment biopsies) samples are analyzed for biomarkers predictive of clinical outcomes, immune function, and anti-tumor humoral immunity by IHC, RT-PCR, flow cytometry, ELISPOT assays, and ELISA.

Eligibility: DISEASE CHARACTERISTICS:
  -  Diagnosis of measurable unresectable stage III or stage IV melanoma
  -  Treated with ipilimumab with or without sargramostim on clinical trial ECOG-E1608
  -  Primary tumor tissue and optional post-treatment biopsies of tumors from easily accessible tissues
  PATIENT CHARACTERISTICS:
  -  ECOG performance status 0 or 1
  PRIOR CONCURRENT THERAPY:
  -  See Disease Characteristics

Relevance to patient case: not relevant
Patient case: 72-year-old male with melanoma; genetic feature: TP53 loss of function

Clinical trial: Trial of pIL-12 Electroporation Malignant Melanoma

Summary: This study will assess the safety and effectiveness of intratumoral plasmid interleukin-12 DNA injection (pIL-12) with electroporation (EP) in malignant melanoma. Intratumoral pIL-12 EP is a gene therapy approach to directly induce a pro-inflammatory response within a tumor to initiate and/or enhance anti-tumor immunity.

Detailed description: Plasmid IL-12 (pIL-12) at a concentration of 0.5 mg/mL will be injected intratumorally at a dose volume of ¼ of the calculated lesion volume and a dose volume per lesion of 0.1 mL for lesions of volume < 0.4 cm3. Six pulses at field strengths of (E+) of 1500 V/cm and pulse width of 100 μs at 1-second intervals will be administered using the OMS to each previously injected tumor.
  Two treatment regimens will be explored:
  Regimen A: Treatment on Days 1, 8 and 15 every 6 weeks Regimen B: Treatment on Days 1, 5 and 8 every 6 weeks. Lesions will be treated on either Regimen A or Regimen B. Subsequent cycles may be given at 6-week intervals, for up to 9 treatment cycles in total.

Eligibility: Inclusion Criteria:
  -  Patients with advanced cutaneous or subcutaneous in-transit or metastatic melanoma
  -  Age ≥ 18 years of age
  -  ECOG performance status 0-2
  -  Patients may have had prior chemotherapy or immunotherapy (vaccines, interferon, ipilimumab, or IL-2) with progression or persistent disease
  -  Patients may have had radiation therapy, but must have progressive disease after radiation therapy if the lesions to be treated are within the radiation field
  -  Female patient of childbearing potential has a negative pregnancy test within 14 days prior to the start of study drug
  -  Adequate organ function
  -  Able to give informed consent
  Exclusion Criteria:
  -  Prior therapy with IL-12 or prior gene therapy
  -  Concurrent immunotherapy, chemotherapy, or radiation therapy for duration of subject participation on study
  -  Evidence of significant active infection (e.g., pneumonia, cellulitis, wound abscess, etc.) at time of study enrollment
  -  Pregnant or breast-feeding women
  -  Patients with electronic pacemakers or defibrillators are excluded from this study
  -  The patient is known to be positive for Human Immunodeficiency Virus (HIV) or has another confirmed or suspected immunosuppressive or immunodeficient condition (patients with thyroiditis are eligible)
  -  Life expectancy of less than 6 months
  -  History of significant cardiovascular disease (i.e. NYHA class 3 congestive heart failure; myocardial infarction with the past 6 months; unstable angina; coronary angioplasty with the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias)
  -  Other clinically significant co-morbidities such as uncontrolled pulmonary disease, uncontrolled diabetes, active CNS disease, active infection or any other condition that could compromise the patients participation in the study according to the investigator

Relevance to patient case: not relevant