araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 67-year-old male with melanoma; genetic feature: BRAF (V600E), NRAS (Q61R)

Clinical trial: Study of Dabrafenib, Trametinib and Metformin for Melanoma Patients

Summary: The main purpose is to evaluate the clinical response, safety and survival of the FDA approved drugs Dabrafenib, Trametinib in combination with Metformin. Investigators hypothesize that the combination of an FDA approved non toxic dose of oral Metformin with the B-Raf inhibitor, Dabrafenib and the MEK inhibitor, Trametinib will yield little toxicity and improve clinical outcomes in terms of objective response rates and survival in metastatic melanoma patients.

Detailed description: The study will be a single-arm, single center, uncontrolled phase I/II trial to estimate the safety of the combined treatments and then estimate the efficacy in terms of objective response rate in patients with stage IIIC and Stage IV melanoma treated with dabrafenib/trametinib and metformin.

Eligibility: Inclusion Criteria:
  -  Male or female patients > 18 years of age
  -  Patients with histologically confirmed BRAFV600E melanoma (Stage IIIC or
  -  Stage IV, American Joint Commission on Cancer)
  -  Eastern Cooperative Oncology Group Performance Status of 0 to 2
  -  Life expectancy > 3 months
  -  At least 1 site of radiographically measurable disease by RECIST 1.1
  -  Adequate hematologic, renal, and liver function as defined by laboratory values performed within 42 days prior to initiation of dosing:
  -  Absolute neutrophil count > 1.0 x 10⁹/L
  -  Platelet count > 50 x 10⁹/L
  -  Hemoglobin > 8 g/dL
  -  Serum creatinine < 2 x upper limit of normal
  -  Total serum bilirubin < 3 x ULN
  -  Serum aspartate transaminase or serum alanine transaminase < 3 x ULN, and < 4 x ULN if liver metastases are present
  -  Fertile males should use an effective method of contraception during treatment and for at least 3 months after completion of treatment, as directed by their physician
  -  Pre-menopausal females and females < 2 years after the onset of menopause should have a negative pregnancy test at Screening. Pre-menopausal females must agree to use an acceptable method of birth control from the time of the negative pregnancy test up to 90 days after the last dose of the study drug
  -  Females of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for > 1 year
  -  Before study entry, written informed consent must be obtained from the patient prior to performing any study related procedures
  Exclusion Criteria:
  -  Prior treatment with Vemurafenib or Dabrafenib
  -  Known hypersensitivity to Metformin or any of its components
  -  Received radiotherapy for non CNS disease within the 2 weeks prior to commencing study treatment or have not recovered from side effects of all radiation related toxicities to Grade < 1, except for alopecia
  -  Pregnant, breast feeding, or refusing double barrier contraception, oral contraceptives, or avoidance of pregnancy measures
  -  Have any other uncontrolled infection or medical condition that could interfere with the conduct of the study

Relevance to patient case: definitely relevant
Patient case: 67-year-old male with melanoma; genetic feature: BRAF (V600E), NRAS (Q61R)

Clinical trial: An Observational Study of BRAF Inhibitors Effectiveness in Patients With Newly Diagnosed Metastatic Melanoma

Summary: This observational study will evaluate the effectiveness of BRAF inhibitors and current therapies in patients with newly diagnosed metastatic melanoma with or without BRAF V600 mutation. Patients will be treated per the locally approved therapeutic options in clinical practice. The observation period for each patient will be up to 24 months.


Eligibility: Inclusion Criteria:
  -  Adult patients, >/= 18 years of age at diagnosis
  -  Histologically confirmed new diagnosis of unresectable or metastatic melanoma
  -  Patients with tumor samples available for assessment of BRAF V600 mutation
  Exclusion Criteria:
  -  Prior systemic therapy for metastatic disease
  -  Participation in interventional clinical trials

Relevance to patient case: possibly relevant
Patient case: 67-year-old male with melanoma; genetic feature: BRAF (V600E), NRAS (Q61R)

Clinical trial: A Single-Arm, Open-Label, Multicenter Clinical Trial With Nivolumab (BMS-936558) for Subjects With Histologically Confirmed Stage III (Unresectable) or Stage IV Melanoma Progressing Post Prior Treatment Containing an Anti-CTLA4 Monoclonal Antibody (CheckMate 172)

Summary: The purpose of this study is to determine the rate and frequency of high-grade (CTCAE v4.0 Grade 3 or higher), treatment-related, select adverse events in subjects with histologically confirmed stage III (unresectable) or stage IV melanoma and progression post prior treatment containing an anti-Cytotoxic T Lymphocyte Antigen (CTLA-4) monoclonal antibody, treated with Nivolumab (BMS-936558) at a dose of 3 mg/kg every two weeks.


Eligibility: For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com
  Inclusion Criteria:
  -  Subjects with histologically confirmed malignant melanoma
  -  Eastern Cooperative Oncology Group (ECOG) Performance Status (PS):
  -  PS 0 to 1
  -  PS 2
  -  Previously treated unresectable stage III or stage IV melanoma as per the American Joint Committee on Cancer 2010 Guidelines regardless of BRAF mutation status
  -  Subjects must have experienced evaluable Response Evaluation Criteria In Solid Tumors (RECIST 1.1)-defined disease progression
  -  Prior treatment with chemotherapy, interferon (adjuvant setting), Interleukin (IL-2), BRAF/MEK inhibitors for subjects with known BRAF mutations, Mitogen-activated or extracellular signal- regulated protein kinase (MEK) inhibitors for Neuroblastoma Ras Viral (v-ras) oncogene homolog (NRAS) mutations, and cKIT inhibitor subjects with known cKIT mutations are allowed
  -  Patients with CNS metastases are eligible:
  -  if CNS metastases are treated, patients are asymptomatic or neurologically returned to baseline
  -  if they have previously untreated CNS metastases and are asymptomatic
  -  if they have leptomeningeal metastases, are treated and asymptomatic or neurologically returned to baseline with life expectancy > 3 months
  -  Patients with a known history of Grades 3-4 immune-related adverse reactions during/after anti-CTLA-4 therapy if all toxicities have resolved at least to Grade 1
  Exclusion Criteria:
  -  Subjects with untreated, active Central Nervous System (CNS) metastases are excluded

Relevance to patient case: possibly relevant
Patient case: 67-year-old male with melanoma; genetic feature: BRAF (V600E), NRAS (Q61R)

Clinical trial: Study to Determine the Feasibility of Sentinel Node Biopsy in Patients With Anal Cancer

Summary: The purpose of this study is assess the technical and operational feasibility of a specialised biopsy technique, sentinel lymph node biopsy (SLNB), in patients with anal cancer.

Detailed description: SLNB is based on the premise that lymphatic dissemination from a tumour occurs in a stepwise fashion, with initial involvement of a primary node, called the sentinel node, before dissemination to the remainder of the lymphatic chain. If the sentinel node is histologically negative, then the remainder of the nodes in the same anatomic region will be at a lower (assumed to be minimal) risk of containing metastases. SLNB is part of standard care for patients with malignant melanoma and with breast cancer but has yet to be prospectively evaluated in patients with anal cancer.
  Currently, the standard way to treat patients with anal cancer is to deliver a combination of chemotherapy and radiation to the tumour at the anus together with 'preventative' (prophylactic) radiotherapy to the lymph glands of the groin and pelvis. There is a growing perception for the need to reduce the morbidity of radiotherapy i.e. current regimens over-treat the patient and one approach is to reduce radiotherapy volume and/or dose where there is an absence or very low risk of nodal metastases.
  This feasibility study is a vital first step in informing the design of a larger study examining the role of SLNB in clinical decision-making and outcomes for patients with anal cancer. In this trial eligible patients will attend for lymphoscintigraphy, to locate the lymph node, before sentinel lymph node removal by surgery. Detection rate of the sentinel node(s) will be the key outcome for the study.

Eligibility: Inclusion Criteria:
  -  Patients with squamous cell carcinoma (SCC) of the anus (any T size and/or those with recurrent disease)
  -  Equivocal lymph node involvement on standard CT staging or magnetic resonance (MR) staging or PET-CT scan, as determined by the anal cancer multidisciplinary team (MDT)
  -  Age >= 18 years
  -  Written informed consent provided by the patient
  Exclusion Criteria:
  -  Patients with unequivocal lymph node involvement on standard CT staging or MR staging, as determined by the anal cancer MDT.
  -  Unfit for surgical biopsy
  -  Patients undergoing palliative treatment
  -  Previous pelvic or inguinal area radiotherapy
  -  Other coincident cancers
  -  Previous inguinal surgery (e.g. hernia repair) with mesh insertion

Relevance to patient case: not relevant
Patient case: 67-year-old male with melanoma; genetic feature: BRAF (V600E), NRAS (Q61R)

Clinical trial: The Oncopanel Pilot (TOP) Study

Summary: The BCCA Oncopanel is a clinical assay being developed to determine genotype status of a prospectively defined set of genes.
  The purpose of this pilot study is to assess the feasibility and effect on clinical-decision-making of the Oncopanel test. Eligible patients are those with advanced lung, colorectal, melanoma and GIST cancers and patients with diagnosed malignancies being considered for clinical trials.

Detailed description: Somatic mutations in solid tumors represent an established means of characterizing malignancies for prognostic, diagnostic and therapeutic purposes. Mutations in EGFR, KRAS, BRAF, and KIT and PDGFRA genes direct therapy in patients with advanced lung, colorectal, melanoma, and GIST tumors, respectively. Known or novel mutations in other genes may also be of clinical significance but are not identified by current genotyping offered to BC Cancer Agency (BCCA) patients. Furthermore, numerous candidate genes have been implicated as potential prognostic and predictive biomarkers in patients with solid tumours. As such, the Oncopanel is a clinical assay being developed to determine genotype status of a prospectively defined set of genes. The following clinically relevant set of genes and exons are included in the Oncpanel: KRAS, EGFR, BRAF, NRAS and HRAS, PIK3CA Signal Transduction Pathway Genes, RAS-RAF-MEK-MAPK Pathway, HER2, IDH1 and IDH2, ALK, TP53, c-KIT, STAT1&3 and PDGFRA. Additional testing on the tumour material will also include analysis of specific gene variants associated with adverse events or response to therapy.
  Numerous studies have documented the presence of circulating tumour DNA (ctDNA) among patients with advanced and early stage malignancies (20-22). The ability to diagnose standard cancer mutations with a blood-based assay (a "liquid biopsy") has not yet been established but presents obvious advantages. The emergence of "resistance" mutations arising in the metastatic tumor or throughout the course of therapy is well documented (21, 22). A blood biopsy may represent more accurate determination of the tumor's genetic features than archival DNA specimen. Adequate tissue specimens can be difficult to obtain from some patients with diagnosed malignancies, particularly lung cancer. A blood biopsy may represent a less invasive and timelier means of diagnosing both standard and translational cancer mutations.

Eligibility: Patients with archival tumor tissue and a known history of invasive malignancies are eligible if they meet one or more of the following criteria:
  -  Advanced colorectal cancer and eligible for standard KRAS testing,
  -  Advanced non-small cell lung cancer and eligible for standard EGFR testing,
  -  Advanced melanoma and eligible for standard BRAF testing,
  -  Gastrointestinal stromal tumors (GISTs) eligible for standard c-KIT and PDGFRA testing,
  -  Being considered for potential eligibility in clinical trial.

Relevance to patient case: possibly relevant
Patient case: 67-year-old male with melanoma; genetic feature: BRAF (V600E), NRAS (Q61R)

Clinical trial: Moletest Clinical Study in Scotland

Summary: To evaluate an iPad based photoimage analysis system (Moletest) for improving discrimination of benign from malignant suspicious skin lesions or moles. Specifically the objective is to demonstrate that the Moletest system is able with a sufficient degree of confidence (95%) to identify lesions which are benign


Eligibility: Inclusion Criteria:
  All patients referred to the Dermatology Department, Lanarkshire Hospitals during a period to be defined for assessment of suspicious skin lesions (cutaneous moles) will be eligible for inclusion in the study. There are no age limits but patients under the age of 18 years will also have their inclusion subject to parental/guardian consent
  Exclusion Criteria:
  There is no exclsion criteria

Relevance to patient case: not relevant
Patient case: 67-year-old male with melanoma; genetic feature: BRAF (V600E), NRAS (Q61R)

Clinical trial: Phase I-II Study With Tumor Molecular Pharmacodynamic (MPD) Evaluation and Pharmacokinetics of PD-0332991 in Patients Suffering Metastatic Melanoma

Summary: An open label multicentre, phase I-II study with tumour molecular pharmacodynamics (MPD) evaluation and pharmacokinetics of PD-0332991 added to vemurafenib in patients suffering metastatic melanoma with BR.
  The main objective is to establish the Maximum Tolerated Dose (MTD) of PD-0332991 when added to standard vemurafenib therapy (960 mg BID). The estimated MTD is defined as the dose of PD-0332991 combined with vemurafenib that will be associated with a prespecified proportion of patients experiencing a Dose-Limiting Toxicity (DLT), ie, 1/3.


Eligibility: Inclusion Criteria:
  -  Age > 18 years
  -  Stage IV or un-resectable stage III melanoma
  -  Presence of BRAF V600E/K mutation and CDNKN2A loss and expression of Rb using immunohistochemistry in a recent metastatic sample (< 6 months)
  -  A previous exposure to BRAF inhibitor or combination of BRAF and MEK inhibitors therapy is allowed unless it has been stopped more than 3 months before study enrolment(This will defined the two strata of the trial)
  -  No previous therapy by MEK inhibitor unless associated with BRAF inhibitors
  -  No previous therapy with the AKT/PI3K pathway inhibitor
  -  Patients should have a tumour available for repeated biopsies for pharmacodynamics evaluation
  -  Life expectancy of > 3 months
  -  ECOG performance status <2
  -  Signed informed consent
  -  Patient with health insurance coverage
  -  No patient under guardianship or curators
  Exclusion Criteria:
  -  Inadequate hepatic function defined as serum bilirubin>25 μmol/l, transaminases > 3.0 times the upper limit of normal (ULN) or 5ULN in cases of liver metastases;
  -  Inadequate bone marrow function defined as absolute neutrophil count<1500/mcl, platelets<150000/mcl and haemoglobin<8g/dL
  -  Inadequate renal function with serum creatinine>2.0mg/dl) and /or creatinine clearance< 60 ml/min
  -  Untreated brain metastases : Patients with brain metastases will be eligible if they have completed treatment 1 months prior to the start of study medication, have discontinued corticosteroid treatment for these metastases for at least 5 days, and are neurologically asymptomatic
  -  Myocardial infarct or unstable angina within the past 6 months
  -  Concomitant take of drugs known to be strong inhibitor or inducers of CYP314
  -  HIV positive.
  -  Chemotherapy, immunotherapy within 4 weeks
  -  Drugs interfering with PD-0332991 and vemurafenib metabolism
  -  Malabsorption syndrome or other condition that would interfere with enteral absorption
  -  Congenital long QT syndrome or screening QTc > 470 msec
  -  Need for chronic corticosteroid therapy of ≥10 mg of prednisone per day

Relevance to patient case: definitely relevant
Patient case: 67-year-old male with melanoma; genetic feature: BRAF (V600E), NRAS (Q61R)

Clinical trial: Use of Exome Sequence Analysis and Circulating Tumour in Assessing Tumour Heterogeneity in BRAF Mutant Melanoma

Summary: Despite recent advances in cancer treatment, little impact has been made on curing as opposed to controlling cancers over the last several decades. Part of the problem is that investigators have an incomplete understanding of how tumours behave as they evolve and in response to treatment. In this trial, the investigators hope to better understand the evolution of BRAF melanoma in response to drugs a patient may have received such as vemurafenib or dabrafenib. Importantly, the investigators want to understand how the tumours evolve resistance to these drugs and whether this can be predicted through blood tests, in particular of the circulating tumour DNA.

Detailed description: Study population: BRAF mutant melanoma patients
  Pre-mortem bloods will be taken from the patient on three occasions at one to thirty days apart from each other, with the first blood draw taking place on the patient's first clinic visit. Six 7 ml EDTA and one 6 ml SST vacutainers of blood (a total of approx. 50 ml of blood) will be taken from the patient.
  When death is expected within the next 48-72 hours, the Medical Oncologist/ Radiation Oncologist/ Hematologist OR delegate will revisit the RAP process with the patient and/or family/substitute decision maker to ensure that they are still in agreement. The patient and the families will also be provided with an additional consent form for participation including blood sampling.

Eligibility: Inclusion Criteria:
  UHN adult patient with BRAF mutant melanoma
  Exclusion Criteria:
  Non BRAF mutant melanoma patient Pediatric patient Non-UHN patient

Relevance to patient case: possibly relevant
Patient case: 67-year-old male with melanoma; genetic feature: BRAF (V600E), NRAS (Q61R)

Clinical trial: Study of Trametinib and Nab-paclitaxel in Patients With Melanoma

Summary: This study will investigate the combination of two drugs, trametinib and nab-paclitaxel, in patients with advanced unresectable or metastatic melanoma. Each drug has shown activity in trials of patients with melanoma. However, the combination of these two drugs has not been studied. In this trial the investigators will determine the maximum dose of the drug combination to be administered to patients with advanced unresectable or metastatic melanoma and examine the safety profile of the drug combination.

Detailed description: While treatment for melanoma has evolved in the last few years, advanced/metastatic melanoma remains an aggressive disease with poor prognosis. Trametinib and nab-paclitaxel have demonstrated single-agent activity in Phase III trials of patients with melanoma. The investigators propose to investigate this drug combination in patients with advanced unresectable or metastatic melanoma. This open-label Phase I study is designed to determine the maximum tolerated dose (MTD), recommended Phase II dose (RP2D), and safety profile of trametinib and nab-paclitaxel given in combination. Patients with melanoma and known BRAF mutation status will receive escalating doses of trametinib and nab-paclitaxel to determine the MTD. Once the MTD is determined an additional 6 patients will be treated at the MTD to establish the dose for future studies.

Eligibility: Inclusion Criteria:
  -  Adults (≥18 years) with histologically or cytologically-confirmed advanced unresectable or metastatic melanoma. BRAF mutation-positive and wild-type tumors are allowed.
  -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  -  Adequate hematologic, renal, and hepatic function
  -  Life expectancy ≥12 weeks
  -  Any pre-existing neuropathy must be <grade 2 per Common Technology Criteria for Adverse Events (CTCAE) version 4.0
  Exclusion Criteria:
  -  More than 1 prior cytotoxic chemotherapy regimen in the metastatic setting
  -  Prior MEK inhibitor therapy (prior BRAF inhibitor allowed)
  -  Prior nab-paclitaxel (prior taxane allowed)
  -  Use of an investigational anti-cancer drug within 21 days or 5 half-lives (whichever is shorter) prior to first dose. A minimum of 10 days after termination of investigational drug is required. Any drug-related toxicity should have resolved to Grade 1 or baseline.
  -  Symptomatic or untreated brain metastases
  -  History of retinal vein occlusion (RVO)

Relevance to patient case: possibly relevant
Patient case: 67-year-old male with melanoma; genetic feature: BRAF (V600E), NRAS (Q61R)

Clinical trial: Clinical Research on the Treatments on Advanced Malignant Melanoma by Combining in Situ Immunotherapy and Laser Therapy

Summary: To evaluate the therapeutic efficacy and the safety for the treatments on malignant melanoma by combining semiantigen dinitrophenyl (DNP) in situ immunotherapy and laser therapy, and carry out monitoring on related immunological parameters of the patients.
  72 patients with stage III (b or c) or stage IV skin (which could not be excised by operations) malignant melanoma were treated by combining simple semiantigen DNP in situ immunotherapy and laser therapy respectively. The changes in peripheral blood CD4+CD25+Treg regulatory T cells (Treg), CD8+T, CD4+ T effector cells, IL-10, TGF-β and other inhibitory cytokines of the patients were detected, the changes in anti-DNP IgG antibody titer was monitored, the relationship between delayed-type hypersensitivity (DTH) and survival was observed, and results of clinical follow-ups were also examined.


Eligibility: Inclusion Criteria:
  -  pathologically diagnosed as malignant melanoma, HMB45 (+～++++), S100 (+～++++);
  -  Basically normal hepatic and renal functions as well as results for blood routine examinations;
  -  Karnofsky score ≥ 60;
  -  Anticipated life span for more than three months;
  -  They were all malignant melanoma patients suffering from skin malignant melanoma of local or distal metastasis unsuitable for operations in their skin;
  -  The therapeutic efficacy was objectively evaluated with reference to the criteria from WHO;
  -  All of the subjects had signed the informed consent and had been submitted and approved by the ethic committee of the hospital, the compliance was good and follow-ups can be easily carried out.

Relevance to patient case: not relevant