araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

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: not relevant
Patient case: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

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: possibly relevant
Patient case: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

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: not relevant
Patient case: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

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: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

Clinical trial: Mohs and Immunofluorescence for Malignant Melanoma In Situ

Summary: The purpose of this study is to determine if immunofluorescence (IF) can effectively identify features of malignant melanoma in situ, on sun-damaged skin, in the setting of Mohs Micrographic Surgery.

Detailed description: The aim of this study is to
  1. Determine the feasibility of using melanocytic markers such as Melanoma antigen recognized by T cells 1 (MART-1) with fluorescence to clear surgical margins when compared to conventional MART-1 immunohistochemistry (IHC) in the setting of MMS for LM (lentigo maligna type melanoma in situ).
  2. Compare the use of a cocktail of immunofluorescent markers such as, but not limited to, Sex-determining Region Y (SRY)-box 10 (SOX10), human melanoma black 45 (HMB-45), and Kiel-67 (Ki-67) to sections only stained with fluorescent MART-1 alone.
  3. Explore the value of using other combinations of immunofluorescent markers such as S-100 with Microphthalmia-associated transcription factor (MiTF), Nestin with Ki-67, and HMB-45 with Lamin.

Eligibility: Inclusion Criteria:
  1. Male or female of any race and at least 18 years of age
  2. Patient with biopsied proven Lentigo maligna (LM) in situ
  3. Patient meets criteria for Mohs Micrographic Surgery (MMS)
  1. The cancer is large
  2. The edges of the cancer (clinical margins) cannot be clearly defined
  3. Prior treatment has failed, i.e. recurrent tumor
  4. The cancer is located in a cosmetically sensitive or functionally critical area of the body (such as eyelids, nose, ears, lips, fingers, toes, and genitals)
  5. The histologic pattern of the cancer is aggressive
  6. The patient is immunosuppressed
  4. Patient with biopsied proven LM in situ located on an anatomic areas appropriate for MMS:
  1. Area H: ''Mask areas'' of face (central face, eyelids [including inner/outer canthi], eyebrows, nose, lips [cutaneous/mucosal/vermillion], chin, ear and periauricular skin/sulci, temple), genitalia (including perineal and perianal), hands, feet, nail units, ankles, and nipples/areola.
  2. Area M: Cheeks, forehead, scalp, neck, jawline, pretibial surface.
  3. Area L: Trunk and extremities (excluding pretibial surface, hands, feet, nail units, and ankles).
  5. Patient able to tolerate surgery
  6. Patient is able to comply with appointments including follow-up appointments
  7. Ability to understand and willingness to sign a written informed consent document
  Exclusion Criteria:
  1. Patients under the age of 18
  2. Patient does not meet criteria for MMS or has LM located in areas that are not accessible with MMS
  3. Patient with previously diagnosed invasive LM
  4. Patients unable to comply with follow-up
  5. Adults unable to consent
  6. Pregnant women
  7. Prisoners

Relevance to patient case: not relevant
Patient case: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

Clinical trial: Automatic Early Melanoma Detection by Ultrahigh Resolution Three Dimensional Optical Coherence Tomography

Summary: The investigators will use optical coherence tomography to detect the ex-vivo tissue image of surgical removed melanoma or other benign pigmented lesions of skin.

Detailed description: The investigators will use an advanced high resolution 3D optical coherence tomography (OCT) technology to observe skin tissue images in ex vivo culture. Parts of melanoma or benign pigmented lesions specimens derived from biopsy or surgical excision specimen will be observed by 3D optical tomography. A tiny tissue fragment of melanoma or benign pigmented lesions will be taken from surgical specimen without interference normal pathological evaluation. The location of melanocytic cells in melanoma or benign tissue fragments will be mapped by the 3D optical coherence tomography (OCT). The 3D optic tomography system utilize a Ce:YAG optical fiber as light source and also combined with confocal microscopy. Taken together, these features made the 3D optic tomography system have very high resolution and suitable for single cell imaging. This study will not interfere with the normal medical practice and had no impact on patient's safety and health. All of the materials will be destroyed once the experiments are done. The enrollment criteria will be dermatological patients who need to surgical intervention.

Eligibility: Inclusion Criteria:
  -  Patients aged older than 20 years old
  -  Patients who had melanoma, melanoma in situ, and/or other benign pigmented lesions,
  -  Patients who had non-melanoma skin cancers (basal cell carcinoma, or squamous cell carcinoma).
  -  Patients who had precancerous skin lesions (Bowen's disease, actinicc keratosis)
  Exclusion Criteria:
  • Pregnant women.

Relevance to patient case: not relevant
Patient case: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

Clinical trial: Quality of Life and Surgical Late Effects of Melanoma Treatment

Summary: Health-related Quality of life in Danish stage IB-III cutaneous melanoma patients.

Detailed description: The aim of the PhD-study is to evaluate, in a large cohort of Danish melanoma patients:
  1. Health-related quality of life assessing psychological, physical and social well-being
  2. Physical long term side effects (lymphoedema, scarring and neuropathic pain)
  3. Lymphoedema assessed by clinical examination and DXA scans

Eligibility: Inclusion Criteria:
  -  AJCC stage IB-III cutaneous melanoma patients
  -  At least one year follow-up after melanoma surgery
  Exclusion Criteria:
  -  Pregnancy
  -  Bilateral axilla or groin melanoma surgery

Relevance to patient case: not relevant
Patient case: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

Clinical trial: A Trial of Trametinib and Panitumumab in RAS/RAF Wild Type Advanced Colorectal Cancer

Summary: This is a phase 2 study (the second phase in testing a new drug or drug combination) to see how useful the combination of two drugs, panitumumab and trametinib, are in patients with advanced colorectal cancer with KRAS, NRAS, or BRAF wild type (genes that are not mutated).
  Panitumumab is a drug that is approved by Health Canada for the treatment of advanced colorectal cancer with KRAS wild type. Panitumumab works by binding to and blocking the protein, epidermal growth factor receptor (EGFR) from working.
  Trametinib is a drug that is approved by Health Canada for the treatment of melanoma with a mutation in the BRAF gene. Trametinib works by binding to and blocking mitogen-activated protein kinase kinase (MEK) 1 and MEK2 from working.
  Previous studies have shown that the combination of panitumumab and trametinib may be more useful in KRAS, NRAS, or BRAF wild type colorectal cancer.


Eligibility: Inclusion Criteria:
  -  18 years of age or older
  -  KRAS/NRAS/BRAF wild type colorectal cancer, not responsive to standard therapies, no approved or curative therapy, refuse standard therapy
  -  Prior 5-FU, oxaliplatin and irinotecan
  -  ECOG Performance Status of 0 or 1
  -  Able to swallow/retain oral drugs
  -  Able and agree to have provide tumor tissue/have biopsies
  -  Agree to use contraception
  -  Not pregnant
  -  Adequate organ system function
  Exclusion Criteria:
  -  Chemotherapy, radiotherapy, immunotherapy, or other anti-cancer therapies <28 days or 5 half lives
  -  Prior EGFR, MEK, or RAF inhibitor or regorafenib
  -  Current use of prohibited medications
  -  Unresolved side effects
  -  GI disease or other condition affecting GI absorption
  -  Mucosal or internal bleeding
  -  Any major surgery <four weeks
  -  HIV, HBV, or HCV positive
  -  Active infection
  -  Leptomeningeal disease
  -  Brain metastases
  -  Unacceptable QTcF interval
  -  Significant uncontrolled arrhythmias
  -  Acute coronary syndromes, myocardial infarction, coronary angioplasty, or stenting or bypass grafting < 6 mos.
  -  Class II, III, or IV heart failure
  -  Other clinically significant ECGs
  -  Intra - cardiac defibrillators
  -  Cardiac metastases
  -  Condition that may interfere with patient safety
  -  Hypersensitivity to study drugs
  -  Severe or uncontrolled systemic diseases
  -  Pregnant or lactating
  -  Retinal vein occlusion
  -  Interstitial lung disease or pneumonitis
  -  Active liver or biliary disease

Relevance to patient case: not relevant
Patient case: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

Clinical trial: Trial of Vemurafenib and Cobimetinib in Patients With Advanced BRAFV600 Mutant Melanoma

Summary: This trial explores the immunologic effects of vemurafenib (BRAF inhibitor) and cobimetinib (MEK inhibitor), administered alone and in combination, to patients with advanced BRAF V600E/K mutant melanoma.


Eligibility: Inclusion Criteria:
  -  Signed informed consent
  -  Signed HIV testing consent
  -  Life expectancy ≥ 12 weeks
  -  Able to swallow pills
  -  ECOG performance status 2 or less
  -  Adequate bone marrow function
  -  Adequate renal function
  -  Adequate liver function
  -  Negative urine pregnancy test within 7 days prior to commencement of dosing in premenopausal women
  -  Histological diagnosis of unresectable AJCC stage III or stage IV, BRAFV600E/K mutant melanoma
  -  Measurable disease
  -  Accessible tumor that can be biopsied
  -  Naive to targeted therapy (Prior immune-based therapy in the adjuvant setting or for advanced disease will be allowed if >2 weeks from study entry)
  Exclusion Criteria:
  -  Active systemic infection
  -  Active autoimmune disease or history of known or suspected autoimmune disease
  -  Active brain metastases or leptomeningeal metastases
  -  Treatment with any immunomodulatory medication within 4 weeks of initiation of study therapy.
  -  Positive test for hepatitis B virus
  -  Positive test for hepatitis C virus
  -  Positive test for human immunodeficiency virus (HIV)
  -  Pregnant, lactating or breast feeding women
  -  Localized radiation therapy within the last 14 days
  -  History of malabsorption
  -  No consumption of the following within 7 days prior to start of treatment:
  -  St. John's wort or hyperforin (potent cytochrome P450 CYP3A4 enzyme inducer)
  -  Grapefruit juice (potent cytochrome P450 CYP3A4 enzyme inhibitor
  -  History or evidence of cardiovascular risk
  -  History or evidence of retinal pathology

Relevance to patient case: possibly relevant
Patient case: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

Clinical trial: Immune Modulation Study in Patients With Metastatic Melanoma Treated With Anti-PD1 Monoclonal Antibodies

Summary: This is an open mono-centric prospective non-randomized study in patients with metastatic melanoma treated with Anti-PD1 monoclonal antibodies (Nivolumab). The aim of the study is to identify the immune cells modulations differences between patients who present a complete, partial or stable response and patients who have non-response to the therapy in order to establish an improving response rate strategy.


Eligibility: Inclusion Criteria:
  -  Men and women aged ≥ 18 years
  -  Patient with metastatic or unresectable melanoma
  -  Anti-PD1 monoclonal antibodies treatment indication
  -  Patient affiliated to a social security regime
  -  Signed Written Informed Consent.
  -  agree with the storage of his biological samples
  -  Women of childbearing potential must as mentioned in the summary of product characteristics (SPC) using two effective methods of contraception during treatment, and men whose partner is of childbearing potential must use effective contraception during treatment. For all patients treated men and women, contraception should be continued during the four months following the discontinuation of nivolumab.
  Exclusion Criteria:
  -  development of haematological tumor during treatment
  -  Patients requiring concomitant chronic treatment with systemic corticosteroids or other immunosuppressive agents
  -  Patients with autoimmune disease.
  -  Patient with Occular melanoma

Relevance to patient case: possibly relevant
Patient case: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

Clinical trial: Study to Analyze Mutations in V600 BRAF Oncogen in Participants With Metastatic Melanoma

Summary: This is a national, multicenter, cross-sectional epidemiological study in adult Spanish participants diagnosed with advanced or metastatic melanoma.


Eligibility: Inclusion Criteria:
  -  Valid tumor samples from participants diagnosed with Stage IIIc or IV melanoma
  -  Written informed consent granted
  Exclusion Criteria:
  - Do not fulfill one or more inclusion criteria

Relevance to patient case: not relevant