araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 80-year-old male with melanoma; genetic feature: BRAF (V600R)

Clinical trial: Phase 1 Safety and Tolerability of MEDI4736 in Combination With Dabrafenib and Trametinib or With Trametinib Alone

Summary: The purpose of this study is to determine the maximum tolerated dose and the safety profile of MEDI4736 in combination with dabrafenib and trametinib or with trametinib alone in subjects with metastatic or unresectable melanoma with BRAF-mutation positive or Wild Type BRAF, respectively.


Eligibility: Inclusion Criteria:
  -  Adults >/= 18 years old
  -  Histologically confirmed cutaneous melanoma that is either Stage IIIc (unresectable) or Stage IV (metastatic) and determined to be BRAF V600E or V600K mutation-positive (cohort A) or mutation-negative (cohorts B and C)
  -  ECOG performance status of 0 or 1
  -  Measurable disease by radiographic or physical examination
  -  Adequate organ and marrow function
  -  Willingness to provide consent for biopsies positive or BRAF WT measurable disease, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and adequate organ and marrow function
  Exclusion Criteria:
  -  Prior treatment with a BRAF inhibitor or MEK inhibitor
  -  Any prior Grade ≥ 3 immune-related adverse event while receiving immunotherapy
  -  Active or prior documented autoimmune disease within the past 2 years
  -  History of or current risk for retinal vein occlusion (RVO) or central serous retinopathy (CSR)
  -  History of or current cardiovascular risk including myocardial infarction, ≥ Class II congestive heart failure, uncontrolled arrhythmias, or refractory hypertension
  -  Active, untreated CNS metastases
  -  Women who are pregnant or lactating

Relevance to patient case: possibly relevant
Patient case: 80-year-old male with melanoma; genetic feature: BRAF (V600R)

Clinical trial: Study to Evaluate Treatment of Dabrafenib Plus Trametinib in Subjects With BRAF Mutation-Positive Melanoma That Has Metastasized to the Brain

Summary: This is a multi-cohort, open label, Phase II study with Dabrafenib (GSK2118436) and Trametinib (GSK1120212) combination therapy in subject with BRAF mutation-positive melanoma that has metastasized to the brain. This study will evaluate the safety and efficacy of 4 cohorts. Cohorts will consist of; V600 E, D, K, R mutations, metastases to the brain, symptomatic and asymptomatic, with or without prior local (brain) therapy, with or without prior local (brain) therapy, and range of ECOG scores from 0-2.


Eligibility: Inclusion Criteria:
  -  ECOG Performance Status range of 0-2
  -  Histologically confirmed cutaneous metastatic melanoma of V600 E, K, D or R.
  -  May be systemic naïve or received up to two previous systemic treatment regimens for metastatic melanoma.
  -  Must be able to undergo MRI and have at least one measurable intracranial lesion for which specific criteria have to be met.
  Exclusion Criteria:
  -  Prior treatment with any BRAF inhibitor or any mitogen-activated protein/extracellular signal-regulated kinase inhibitor.
  -  Anti-cancer therapy or investigational anti-cancer therapy or chemotherapy without delayed toxicity within treatment specific timeframe.
  -  Treatment with stereotactic radiosurgery or treatment with whole-brain radiation within treatment specific timeframe.
  -  Any presence of leptomeningeal disease or any parenchymal brain metastasis
  -  History of another malignancy, some exceptions may apply.
  -  A history or evidence of cardiovascular risk- specific criteria have to be met
  -  A history or current evidence/risk of retinal vein occlusion or retinal pigment epithelial detachment - specific criteria have to be met.

Relevance to patient case: definitely relevant
Patient case: 80-year-old male with melanoma; genetic feature: BRAF (V600R)

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: definitely relevant
Patient case: 80-year-old male with melanoma; genetic feature: BRAF (V600R)

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: 80-year-old male with melanoma; genetic feature: BRAF (V600R)

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: 80-year-old male with melanoma; genetic feature: BRAF (V600R)

Clinical trial: A Translational Systems Medicine Approach to Provide Predictive Capacity for Therapy Response in Advanced or Metastatic Malignant Melanoma

Summary: This is an exploratory prospective translational multicentre study. Melanoma is the 5th most common cancer diagnosed in Ireland and its incidence among women and men is above the European average.
  Following treatment the elimination of cancer cells ultimately occurs by the activation of apoptotic cell death pathways. The SYS-ACT approach builds on a combination of mathematical systems of modelling, quantitative biochemistry and cell biology, and specifically predicts the drug responsiveness of melanoma cell lines to various apoptosis-inducing treatments.
  The investigators propose to validate the SYS-ACT approach and application in a translational systems medicine study.


Eligibility: Inclusion Criteria:
  1. Patients ≥ 18 years of age.
  2. Patient must be able to give own signed informed consent.
  3. Patients that present with advanced or metastatic (stage III/IV) malignant melanoma of the skin.
  4. Patients that are planned to receive either:
  -  Adjuvant treatment
  -  1st line treatment for metastatic disease
  -  2nd line treatment for metastatic disease
  5. Patients with prior adjuvant treatment are allowed.
  6. Patients receiving planned standard treatment of one or more of the following:
  -  Chemotherapy regimens containing DTIC, TMZ and/or cisplatin
  -  Immunotherapy (for example ipilimumab and/or anti-PD-L1/PD-1 therapies)
  -  BRAF and/or MEK inhibitors
  7. Patients were FFPE and fresh frozen tissue is available (both mandatory).
  Exclusion Criteria:

Relevance to patient case: possibly relevant
Patient case: 80-year-old male with melanoma; genetic feature: BRAF (V600R)

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: 80-year-old male with melanoma; genetic feature: BRAF (V600R)

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: 80-year-old male with melanoma; genetic feature: BRAF (V600R)

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: 80-year-old male with melanoma; genetic feature: BRAF (V600R)

Clinical trial: Inducing Systemic Immunity and Regressions in Metastatic Melanoma

Summary: In patients with multiple metastatic nodules of melanoma, the investigators evaluated whether autologous cytokines injected into cutaneous metastases would induce a systemic immune response as evidenced by the accumulation of dense lymphocytic infiltrates in metastases that had never been injected. Such immune responses were observed, and often the never-injected metastasis regressed completely. 20% of patients remained free of disease for greater than 5 years.

Detailed description: Lymphocytic infiltrates were seen in never-injected nodules only after several weeks of injections elsewhere. No adverse events were seen. The tumor-infiltrating lymphocytes were able to kill autologous melanoma ex vivo. Some patients who experienced complete regressions of all metastases lived without disease for over 10 years.

Eligibility: Inclusion Criteria:
  -  Multiple cutaneous or subcutaneous metastases of melanoma
  Exclusion Criteria:
  -  Visceral metastases on admission.
  -  No current chemotherapy or immunotherapy.
  -  Note study performed between 1978 and 2002 before current therapies were available.

Relevance to patient case: not relevant
Patient case: 80-year-old male with melanoma; genetic feature: BRAF (V600R)

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