araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 45-year-old female with Melanoma. Genetic variant: BRAF (V600E), CDKN2A Deletion. Other conditions: None.

Clinical trial: First-line FOLFOXIRI Plus Bevacizumab in BRAF Mutant Metastatic Colorectal Cancer

Summary: The purpose of this study is to prospectively verify if FOLFOXIRI plus bevacizumab as first-line treatment could be considered a promising approach to improve the outcome of BRAF mutant metastatic colorectal cancer patients


Eligibility: Inclusion Criteria:
  -  Histologically confirmed colorectal adenocarcinoma;
  -  Availability of formalin-fixed paraffin embedded tumor block from primary and/or metastasis;
  -  BRAF V600E mutant status of primary colorectal cancer and/or related metastasis;
  -  Unresectable and measurable metastatic disease according to RECIST criteria;
  -  Male or female, aged > 18 years and < 75 years;
  -  ECOG PS < 2 if aged < 71 years;
  -  ECOG PS = 0 if aged 71-75 years;
  -  Life expectancy of more than 3 months;
  -  Adequate haematological function: ANC ≥ 1.5 x 10^9/L; platelets ≥ 100 x 10^9/L, Hb ≥ 9 g/dL;
  -  Adequate liver function: serum bilirubin ≤ 1.5 x ULN; alkaline phosphatase and transaminases ≤ 2.5 x ULN (in case of liver metastases ≤ 5 x ULN);
  -  Serum creatinine ≤ 1.5 x ULN;
  -  Previous adjuvant chemotherapy is allowed if more than 12 months have elapsed between the end of adjuvant therapy and first relapse;
  -  At least 6 weeks from prior extended radiotherapy and 4 weeks from surgery;
  -  Written informed consent to experimental treatment and molecular analyses.
  Exclusion Criteria:
  -  Presence or history of CNS metastasis;
  -  Serious, non-healing wound, ulcer, or bone fracture;
  -  Evidence of bleeding diathesis or coagulopathy;
  -  Uncontrolled hypertension;
  -  Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (CVA) (≤6 months before treatment start), myocardial infarction (≤ 6 months before treatment start), unstable angina, NYHA ≥ grade 2 chronic heart failure (CHF), uncontrolled arrhythmia;
  -  Current or recent (within 10 days prior to study treatment start) ongoing treatment with anticoagulants for therapeutic purposes;
  -  Chronic, daily treatment with high-dose aspirin (>325 mg/day);
  -  Symptomatic peripheral neuropathy ≥ 2 grade NCIC-CTG criteria;
  -  Active uncontrolled infections;
  -  Treatment with any investigational drug within 30 days prior to enrolment;
  -  Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of curatively treated basal and squamous cell carcinoma of the skin or in situ cancer of the cervix;
  -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start;
  -  Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome;
  -  Fertile women (< 2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception.

Relevance to patient case: not relevant
Patient case: 45-year-old female with Melanoma. Genetic variant: BRAF (V600E), CDKN2A Deletion. Other conditions: None.

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: 45-year-old female with Melanoma. Genetic variant: BRAF (V600E), CDKN2A Deletion. Other conditions: None.

Clinical trial: Vemurafenib (R05185426) in Poor Performance Status Patients With Unresectable Locally Advanced or Metastatic Melanoma Harboring a V600E/K Mutation

Summary: The purpose of this study is to find out what effects, good and/or bad, vemurafenib has on the patient and the melanoma. Specifically, the investigators want to know how well vemurafenib shrinks melanoma. The investigators also want to find out how well vemurafenib can improve how well the patient functions.


Eligibility: Inclusion Criteria:
  -  Age >18 years old.
  -  Histologic proof of melanoma reviewed and confirmed by MSKCC.
  -  A confirmed EBRAFV600E or KBRAFV600K mutation.
  -  Stage IV melanoma, or advanced stage III not curable by surgery. Patients with active CNS metastases will be allowed on the study.
  -  Measurable disease by RECIST v1.1.
  -  ECOG performance status 3 or 4. The basis for the grading of performance is strict; there must be clear justification of the performance status grade (e.g. patient is confined to bed > 50% of time, or cannot carry out ADLs, or is otherwise disabled by burden of disease such as requiring supplemental O2).
  -  Patients must be able to swallow pills
  -  Adequate hematologic, hepatic and renal function as defined by the following:
  -  Absolute Neutrophil Count ≥ 1.0 x 109/L
  -  Hemoglobin ≥8.0g/dL, occasional transfusions are acceptable as vemurafenib does not have significant hematologic toxicities.
  -  Total bilirubin ≤2.0x the upper limit of normal, ≤3.0x the upper limit of normal if the patient has Gilbert's Syndrome.
  -  Alkaline phosphatase ≤2.0x the upper limit of normal.
  -  AST and ALT ≤2.0x the upper limit of normal.
  -  Serum creatinine ≤ 1.5x the upper limit of normal.
  Exclusion Criteria:
  -  Uveal melanoma as primary.
  -  Concurrent chemotherapy, immunotherapy, or radiotherapy.
  -  Prior treatment with a RAF inhibitor. Other prior chemotherapy, immunotherapy, or radiotherapy will be allowed including prior treatment with a MEK inhibitor Patients must have had complete recovery from any adverse events or toxicities of prior cancer-directed therapies.
  -  Pregnant or lactating women.
  -  A second active malignancy. Prior malignancy will be allowed as long as the patient is known to be free of disease for at least 2 years. Patients with indolent B-cell malignancies will not be eligible.
  -  QTc interval > 500 msec.

Relevance to patient case: not relevant
Patient case: 45-year-old female with Melanoma. Genetic variant: BRAF (V600E), CDKN2A Deletion. Other conditions: None.

Clinical trial: Comparative Microarray Analysis in Primary Cutaneous Malignant Melanoma

Summary: Perturbations in microRNA (miRNA) expression profiles has been reported for cutaneous malignant melanoma (CMM). This study will be an exploratory analysis by miRNA expression profiling using microarrays.

Detailed description: Perturbations in microRNA (miRNA) expression profiles has been reported for cutaneous malignant melanoma (CMM). With regards to a rapidly growing number of newly discovered miRNA sequences, the availability of up-to-date miRNA expression profiles for primary cutaneous malignant melanoma (PCMM), cutaneous malignant melanoma metastases (CMMM) and benign melanocytic naevi (BMN) is limited. Patients with PCMM, CMMM and BMN are included in the study to perform an exploratory analysis by miRNA expression profiling using microarrays. Expression levels of miRNA candidates will be validated by TaqMan real-time quantitative polymerase chain reaction (RT-PCR).

Eligibility: Inclusion Criteria:
  -  Primary Cutaneous Malignant Melanoma
  -  Cutaneous Malignant Melanoma Metastases
  -  Benign Melanocytic Naevi
  Exclusion Criteria:
  - Other Skin Cancer than Primary Cutaneous Malignant Melanoma

Relevance to patient case: not relevant
Patient case: 45-year-old female with Melanoma. Genetic variant: BRAF (V600E), CDKN2A Deletion. Other conditions: None.

Clinical trial: Minimally Invasive Groin Dissection for Melanoma

Summary: The purpose of this this study is to determine if a structured educational training program is successful in teaching surgeons a new operative technique. It will then be determined if this new operative technique is safe.

Detailed description: This study is a multi-center, Phase 1 clinical trial to determine the safety and feasibility of minimally invasive inguinal lymph node dissection for patients with melanoma. Licensed surgeons who have undergone special training, including a course at the Mayo Clinic Rochester in minimally invasive lymph node dissection (MILND) will perform the new procedure at their home institutions. The study will characterize the learning curve of MILND in the clinical setting, and evaluate the safety of the new operative technique.
  The hypotheses for this study are: 1) minimally invasive groin dissection is a safe procedure. 2) a structured educational training program is a feasible and effective method to train practicing surgeons in this novel procedure and 3) pre-course generic laparoscopic technical skills correlate with minimally invasive superficial groin dissection performance in a clinical setting, including operative oncologic standards and safety metrics.

Eligibility: Inclusion criteria:
  -  Malignant melanoma present in an inguinal nodal basin requiring superficial inguinal lymph node dissection.
  -  Plan for superficial inguinal dissection alone or combined superficial inguinal and deep pelvic node dissection is acceptable.
  -  Clinical or radiographic evidence of superficial inguinal lymph node disease or a prior positive single lymph node biopsy of the superficial inguinal basin as an indication for superficial inguinal lymph node disease is acceptable.
  -  Patients must be Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 and be healthy enough to undergo a general anesthetic (no epidural or spinal anesthetics).
  -  Female patients of child bearing age must have a negative pregnancy test, be surgically sterile or post-menopausal greater than 1 year.
  -  Patients must be able to return to surgical facility for 30 and/or 90 day (+/- 20 days) for follow-up appointment.
  Exclusion Criteria:
  -  Prior ipsilateral superficial inguinal lymph node dissection
  -  Invasion or ulceration of inguinal nodal disease into the overlying skin
  -  Prior radiation therapy to the same regional nodal basin.

Relevance to patient case: not relevant
Patient case: 45-year-old female with Melanoma. Genetic variant: BRAF (V600E), CDKN2A Deletion. Other conditions: None.

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
Patient case: 45-year-old female with Melanoma. Genetic variant: BRAF (V600E), CDKN2A Deletion. Other conditions: None.

Clinical trial: A Multi-National, Prospective, Observational Study in Patients With Unresectable or Metastatic Melanoma

Summary: The purpose of this study is to examine the safety of Ipilimumab and patterns of use in the treatment of unresectable or metastatic melanoma in the post-approval setting.

Detailed description: Time Perspective: this study does have a retrospective component involving a subset of patients.

Eligibility: For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.
  Inclusion Criteria:
  -  Diagnosis of unresectable or metastatic melanoma
  -  Age of 18 years or older at time of entry into the study
  -  Patients who have initiated treatment for unresectable or metastatic melanoma at medical practice (e.g. community-based, office-based, hospital-based, academic setting)within 21 days before informed consent for this study OR in the case where treatment has not yet been initiated, documentation that the treatment strategy was determined before informed consent for this study, and treatment must be initiated within 28 days after informed consent
  -  Ipilimumab-treated patients must be receiving treatment for the indication(s) approved in their country of residence or where they are receiving treatment
  Exclusion Criteria:
  -  Current or pending participation in a clinical trial examining therapy for the treatment of any cancer (including unresectable or metastatic melanoma)
  -  Current use of therapy to treat a primary cancer other than melanoma

Relevance to patient case: not relevant
Patient case: 45-year-old female with Melanoma. Genetic variant: BRAF (V600E), CDKN2A Deletion. Other conditions: None.

Clinical trial: BRIM-P: A Study of Vemurafenib in Pediatric Patients With Stage IIIC or Stage IV Melanoma Harboring BRAFV600 Mutations

Summary: This open-label, multicenter. single arm Phase I dose-escalation study with efficacy tail extension will evaluate the maximum tolerated dose/recommended dose, the safety and efficacy of vemurafenib (RO5185426) in pediatric participants (aged 12 through 17) with newly diagnosed or recurrent surgically incurable and unresectable Stage IIIC or Stage IV melanoma harboring BRAFV600 mutations. Participants will receive vemurafenib orally twice daily until disease progression or unacceptable toxicity occurs.


Eligibility: Inclusion Criteria:
  -  Pediatric participants, 12 to 17 years of age inclusive
  -  Histologically confirmed surgically incurable and unresectable Stage IIIC or Stage IV (AJCC) melanoma
  -  Positive proto-oncogene B-Raf (BRAF) mutation result (Cobas 4800 BRAF V600 Mutation Test)
  -  Measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria
  -  Performance status: Karnofsky (for participants >/= 16 years of age) or Lansky (for participants < 16 years of age) score of >/= 60
  -  Adequate bone marrow, liver and renal function
  -  Participants must have fully recovered from the acute toxic effects of all prior therapy prior to first administration of study drug
  Exclusion Criteria:
  -  Active or untreated central nervous system (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 selective/specific BRAF or Methyl Ethyl Ketone (MEK) inhibitor (previous treatment with sorafenib is allowed)
  -  Any previous treatment with study drug (RO5185426) or participation in a clinical trial that includes RO5185426
  -  Pregnant or lactating females
  -  Known human immunodeficiency virus (HIV) positivity or acquired immune deficiency syndrome (AIDS)-related illness, active hepatitis B virus, or active hepatitis C virus

Relevance to patient case: not relevant
Patient case: 45-year-old female with Melanoma. Genetic variant: BRAF (V600E), CDKN2A Deletion. Other conditions: None.

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: 45-year-old female with Melanoma. Genetic variant: BRAF (V600E), CDKN2A Deletion. Other conditions: None.

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