araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 38-year-old male with melanoma; genetic feature: BRAF (K601E)

Clinical trial: Dabrafenib Plus Trametinib vs Vemurafenib Alone in Unresectable or Metastatic BRAF V600E/K Cutaneous Melanoma

Summary: This is a two-arm, open-label, randomised, Phase III study comparing dabrafenib (GSK2118436) and trametinib (GSK1120212) combination therapy to vemurafenib. Subjects with histologically confirmed cutaneous melanoma that is either stage IIIc (unresectable) or stage IV, and BRAF V600E/K mutation positive will be screened for eligibility. Subjects who have had prior systemic anti-cancer treatment in the advanced or metastatic setting will not be eligible although prior systemic treatment in the adjuvant setting will be allowed. Approximately 694 subjects will be randomised 1:1 (combination therapy:vemurafenib). The primary endpoint is overall survival (OS) for subjects receiving the combination therapy compared with those receiving vemurafenib.


Eligibility: Inclusion Criteria:
  -  >= 18 years of age
  -  Stage IIIc or Stage IV BRAF V600E/K cutaneous melanoma
  -  Measurable disease according to RECIST 1.1
  -  Women of childbearing potential with negative serum pregnancy test prior to randomisation
  -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  -  Adequate baseline organ function
  Exclusion Criteria:
  -  Any prior use of a BRAF or MEK inhibitor
  -  Prior systemic anti-cancer treatment in the advanced or metastatic setting; prior systemic treatment in the adjuvant setting is allowed
  -  History of another malignancy (except subjects who have been disease free for 3 years or with a history of completely resected non-melanoma skin cancer)
  -  Known HIV, HBV, HCV infection (except chronic or cleared HBV and HCV infection which will be allowed)
  -  Brain metastases (except if all known lesions were previously treated with surgery or stereotactic radiosurgery and lesions, if still present, are confirmed stable for >= 12 weeks prior to randomisation or if no longer present are confirmed no evidence of disease for >= 12 weeks, and are asymptomatic with no corticosteroid requirements for >= 4 weeks prior to randomisation, and no enzyme inducing anticonvulsants for >= 4 weeks prior to randomisation
  -  History or evidence of cardiovascular risk (LVEF < LLN; QTcB >= 480 msec; blood pressure or systolic >=140 mmHg or diastolic >= 90 mmHg which cannot be controlled by anti-hypertensive therapy)
  -  History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR)

Relevance to patient case: not relevant
Patient case: 38-year-old male with melanoma; genetic feature: BRAF (K601E)

Clinical trial: BRIM8: A Study of Vemurafenib Adjuvant Therapy in Patients With Resected Cutaneous BRAF Mutant Melanoma

Summary: This multicenter, randomized, double-blind, placebo-controlled study will evaluate the efficacy and safety of vemurafenib in participants with completely resected, cutaneous BRAF mutation-positive melanoma at high risk for recurrence. Participants will be randomized to receive oral doses of vemurafenib 960 milligrams (mg) twice daily or matching placebo. The anticipated time on study treatment is 52 weeks.


Eligibility: Inclusion Criteria:
  -  Histologically confirmed melanoma of cutaneous origin
  -  Surgically rendered free of disease within 90 days of randomization
  -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  -  Life expectancy of at least 5 years
  -  Fully recovered from the effects of any major surgery or significant traumatic injury prior to the first dose of study treatment
  -  Adequate hematologic, hepatic, and renal function
  Exclusion Criteria:
  -  History of any systemic or local therapy (e.g., chemotherapy, biologic or targeted therapy, hormonal therapy, or photodynamic therapy) for the treatment or prevention of melanoma, including interferon alpha-2b and pegylated interferon alpha-2b
  -  History of limb perfusion therapy
  -  History of radiotherapy for the treatment of melanoma
  -  Invasive malignancy other than melanoma at the time of enrollment or within 5 years prior to first dose of study treatment
  -  Family history of inherited colon cancer syndromes
  -  History of clinically significant cardiac or pulmonary dysfunction
  -  Major surgical procedure within 4 weeks prior to first dose of study treatment
  -  Infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C virus

Relevance to patient case: not relevant
Patient case: 38-year-old male with melanoma; genetic feature: BRAF (K601E)

Clinical trial: A Non-Drug Study on the Relationship Between Exploratory Biomarkers and Functional Dimensions in Individuals With Autistic Disorder or Asperger's Syndrome

Summary: This multi-center, non-drug study will explore the relationship between exploratory biomarkers and functional dimensions in male adult individuals with Autistic Disorder or Asperger's Syndrome and healthy volunteer controls. Subjects will undergo a number of assessments on study visit Day 1.


Eligibility: Inclusion Criteria:
  Individuals with Autistic Disorder or Asperger's Syndrome:
  -  Male adults, 18 to 45 years of age inclusive
  -  Diagnosis of Autistic Disorder or Asperger's Syndrome as defined by DSM-IV
  -  IQ >70
  -  Body mass index (BMI) 18 to 35 kg/m2
  -  Availability of a reliable caregiver, able and willing to provide information regarding the individual's behavior and symptoms
  Healthy controls:
  -  Healthy male adults, 18 to 45 years of age inclusive
  -  IQ >70
  -  Body mass index (BMI) 18 to 30 kg/m2
  Exclusion Criteria:
  General exclusion criteria:
  -  Positive test for drugs of abuse or alcohol
  -  Confirmed systolic blood pressure >140 or <90 mmHg, and diastolic blood pressure >90 or <50 mmHg
  -  Resting pulse rate >100 or <40 beats per minute
  -  Alcohol and/or substance abuse/dependence during the last 12 months
  -  Concomitant disease or condition that could interfere with, or treatment of which might interfere with, the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study
  Additionally for individuals with Autistic Disorder or Asperger's Syndrome:
  -  History of epilepsy/seizure disorder (except simple febrile seizures)
  -  Significant disruptive, aggressive or self-injurious, or sexually inappropriate behavior during the last 3 months that in the opinion of the investigator might interfere with the conduct of the study
  Additionally for healthy controls:
  -  Clinically significant abnormalities in laboratory test results
  -  History of or current psychiatric, neurological disorder or pervasive developmental disorder

Relevance to patient case: not relevant
Patient case: 38-year-old male with melanoma; genetic feature: BRAF (K601E)

Clinical trial: Phase II Safety Study of Vemurafenib Followed by Ipilimumab in Subjects With V600 BRAF Mutated Advanced Melanoma

Summary: The purpose of this study is to assess the safety profile of vemurafenib, 960 mg, administered for 6 weeks, followed by ipilimumab monotherapy in patients with BRAF V600 mutated advanced/metastatic melanoma.


Eligibility: For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com
  Key Inclusion Criteria:
  -  Men and women 18 years of age and older
  -  Histologic diagnosis of malignant melanoma tested positive for the BRAF V600 mutation
  -  Previously untreated unresectable Stage III or Stage IV melanoma
  -  Complete set of brain/neck, chest, abdomen/pelvis axial radiographs taken within 28 days of first dose of study drug
  -  Measurable melanoma by physical or radiographic examination
  -  Brain metastases stable after radiation for at least 1 month and off corticosteroid therapy for ≥30 days prior to enrollment
  -  Eastern Cooperative Oncology Group performance status of 0 or 1
  -  Adequate hematologic parameters and renal and hepatic function
  Key Exclusion Criteria:
  -  Primary ocular melanoma
  -  Active brain metastases with symptoms or requiring corticosteroid treatment
  -  Any other malignancy from which the patient has been disease-free for less than 2 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix
  -  History of or current active autoimmune diseases, including but not limited to inflammatory bowel diseases, rheumatoid arthritis, autoimmune thyroiditis, autoimmune hepatitis, systemic sclerosis, systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies
  -  History of or current immunodeficiency disease, splenectomy, or splenic irradiation
  -  Prior anticancer therapy or investigational products <4 weeks prior to enrollment
  -  Prior therapy with a BRAF or MEK inhibitor and prior investigational anticancer immunotherapies;
  -  Prior therapies with immunosuppressive agents within the past 2 years
  -  Concomitant therapy with any anticancer or potent immunosuppressive agent, surgery, radiotherapy, other investigational anticancer therapies, or chronic use of systemic corticosteroids

Relevance to patient case: not relevant
Patient case: 38-year-old male with melanoma; genetic feature: BRAF (K601E)

Clinical trial: A Study of the BRAF Inhibitor Dabrafenib in Combination With the MEK Inhibitor Trametinib in the Adjuvant Treatment of High-risk BRAF V600 Mutation-positive Melanoma After Surgical Resection.

Summary: This is a two-arm, randomized, double-blind Phase III study of dabrafenib in combination with trametinib versus two placebos in the adjuvant treatment of melanoma after surgical resection. Patients with completely resected, histologically confirmed, BRAF V600E/K mutation-positive, high-risk [Stage IIIa (lymph node metastasis >1 mm), IIIb or IIIc] cutaneous melanoma will be screened for eligibility. Subjects will be randomized to receive either dabrafenib (150 milligram (mg) twice daily [BID]) and trametinib (2 mg once daily [QD]) combination therapy or two placebos for 12 months.


Eligibility: Inclusion Criteria:
  -  Completely resected histologically confirmed high-risk [Stage IIIa (LN metastasis more than 1 mm), IIIb or IIIc cutaneous melanoma determined to be V600E/K mutation positive by a central laboratory. Patients presenting with initial resectable lymph node recurrence after a diagnosis of Stage I or II melanoma are eligible.
  -  Surgically rendered free of disease no more than 12 weeks before randomization.
  -  Recovered from definitive surgery (e.g. no uncontrolled wound infections or indwelling drains).
  -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
  -  Adequate hematologic, hepatic, renal and cardiac function.
  Exclusion Criteria:
  -  Known mucosal or ocular melanoma or the presence of unresectable in-transit metastases.
  -  Evidence of distant metastatic disease.
  -  Prior systemic anti-cancer treatment and radiotherapy for melanoma; prior surgery for melanoma is allowed.
  -  History of another malignancy or concurrent malignancy including prior malignant melanoma. Exceptions to this include: Patients who have been disease-free for 5 years or patients with a history completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible, for example cervical cancer in situ, atypical melanocytic hyperplasia or melanoma in situ, multiple primary melanomas, or other malignancies for which the patient has been disease free for > 5 years.
  -  History or current evidence of cardiovascular risk.
  -  History or current evidence of retinal vein occlusion (RVO) or central serous retinopathy (CSR)

Relevance to patient case: not relevant
Patient case: 38-year-old male with melanoma; genetic feature: BRAF (K601E)

Clinical trial: Safety and Efficacy of LEE011 and LGX818 in Patients With BRAF Mutant Melanoma.

Summary: To evaluate the safety, tolerability and efficacy of LEE011 and LGX818 when administered orally to patients with BRAF mutant melanoma.

Detailed description: In response to developments in the treatment of melanoma, the sponsor reviewed the data from the ongoing study and decided to halt further enrollment of patients in the Phase Ib part of the study. Consequently, the Phase II part of the study was not performed. Early termination of the study was not due to any safety concerns.

Eligibility: Inclusion Criteria:
  -  Age ≥18 years.
  -  Diagnosis of locally advanced or metastatic melanoma along with written documentation of BRAF V600 mutation.
  -  ECOG performance status of 0 - 2.
  -  Patients enrolled into Phase Ib must have evidence of evaluable and/or measurable disease as determined by RECIST v1.1.
  -  Patients enrolled into Phase II (BRAFi naïve and resistant) must have evidence of measurable disease as determined by RECIST v1.1.
  -  Archival tumor tissue must be obtained for patients enrolled in Phase Ib and Phase II arm 1a/b- BRAFi naïve patients. If an archival tumor tissue is not available, a fresh tumor sample is acceptable.
  -  For patients enrolled in the phase II arm 2, patients must agree to undergo a fresh tumor biopsy unless one was collected prior to study entry but at the time of disease relapse from the most recent BRAFi treatment.
  Exclusion Criteria:
  -  Symptomatic brain metastases.
  -  Symptomatic or untreated leptomeningeal disease.
  -  Patients with inadequate laboratory values during screening.
  -  In the phase II BRAFi naïve arms (1a/b), prior exposure to CDK4/6 inhibitor (e.g., PD 0332991)
  -  Impaired cardiac function or clinically significant cardiac diseases.
  -  Impairment of gastro-intestinal (GI) function or GI disease that may significantly alter the absorption of LEE011 or LGX818.
  -  Patients with concurrent severe and/or uncontrolled concurrent medical conditions.
  -  Previous or concurrent malignancy.
  -  Major surgery < 2 weeks before starting study treatment
  -  Known diagnosis of human immunodeficiency virus (HIV) or hepatitis C.
  Other protocol-defined inclusion/exclusion criteria may apply.

Relevance to patient case: not relevant
Patient case: 38-year-old male with melanoma; genetic feature: BRAF (K601E)

Clinical trial: A Phase 1b Open Label, Dose Escalation Study of PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma

Summary: The purpose of this research study is to test the safety of an investigational new drug called PLX3397 when used in combination with Vemurafenib (Zelboraf™) at different dose levels. Vemurafenib has been approved by the United States Food and Drug Administration (FDA)/European Medicines Agency (EMA) for the treatment of a specific category of unresectable or metastatic melanoma.


Eligibility: Inclusion Criteria:
  -  Male or female ≥18 years old.
  -  Patients with histologically confirmed unresectable Stage III or Stage IV metastatic melanoma who have not been previously treated with a selective BRAF inhibitor.
  -  Presence of a BRAF V600 mutation in the tumor tissue using the cobas BRAF mutation assay or comparable standard of care methodology.
  -  Measurable disease per RECIST v. 1.1 criteria.
  -  ECOG performance status 0 or 1.
  Exclusion Criteria:
  -  Radiation therapy within 14 days of C1D1.
  -  Investigational drug use within 28 days of C1D1.
  -  Patients with active CNS lesions are excluded (i.e., those with radiographically unstable, symptomatic lesions). However, patients treated with stereotactic therapy or surgery are eligible if they remain without evidence of disease progression in the brain for ≥3 weeks.

Relevance to patient case: not relevant
Patient case: 38-year-old male with melanoma; genetic feature: BRAF (K601E)

Clinical trial: Utility of Novel BRAF Test for Melanoma

Summary: This primary purpose of this study is to obtain blood samples from participants with both early and later stages of melanoma (Stage II/III and Stage IV). The researchers hope to better understand an abnormal protein found in many melanoma tumors called the BRAFV600 mutation.
  There will be two separate cohorts (groups) of participants on this study. You will be placed in one of the Groups.
  Group 1-For participants with advanced melanoma: Your existing tumor tissue sample will be compared to the blood samples given in order to further analyze and to understand the BRAFV600E gene mutation.
  Group 2-For participants with stage II/III melanoma: Following surgery, blood samples will be collected and analyzed.
  Understanding the BRAFV600E gene mutation in melanoma will help the researchers better understand the disease, and help plan treatment options for people with melanoma of all stages in the future.

Detailed description: There will be no extra clinic visits for this study. These research blood samples will be drawn at the same time as your regularly scheduled blood draws that are part of standard care for melanoma.
  About 2 to 4 teaspoons of blood will be drawn for each research sample.
  Depending on which group you are in, you will have either a one time blood draw or ongoing blood work for 1-2 years.

Eligibility: Inclusion Criteria:
  -  Biopsy proven advanced (unresectable stage IIIC or stage IV)or high risk (stage II or stage III) malignant melanoma
  Exclusion Criteria:
  -  History of a different malignancy except for the following circumstances: disease-free for at least 2 years and deemed by the investigator to be at low risk for recurrence; or non-metastatic prostate cancer, cervical cancer in situ and basal cell or squamous cell carcinoma
  -  Known history of a different BRAF mutant malignancy

Relevance to patient case: possibly relevant
Patient case: 38-year-old male with melanoma; genetic feature: BRAF (K601E)

Clinical trial: A Study on the Effect of Vemurafenib on the Pharmacokinetics of a Single Dose of Tizanidine in Patients With BRAFV600 Mutation-Positive Metastatic Malignancies

Summary: This open-label, multicenter, 3-period, fixed-sequence study will evaluate the effect of multiple oral doses of vemurafenib on the pharmacokinetics of a single oral dose of tizanidine in participants with BRAFV600 mutation-positive metastatic malignancies. Participants will receive a single oral dose of tizanidine on Day 1, vemurafenib orally twice daily on Days 2 to 21, and tizanidine and vemurafenib on Day 22. Eligible participants will have the option to continue treatment with vemurafenib as part of an extension study (NCT01739764).


Eligibility: Inclusion Criteria:
  -  Adults 18 to 70 years of age, inclusive
  -  Unresectable Stage IIIc or IV metastatic melanoma positive for the BRAFV600 mutation or other malignant tumor type which harbors a V600 activating mutation of BRAF, as determined by Cobas 4800 BRAFV600 Mutation Test or a DNA sequencing method
  -  Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
  -  Life expectancy greater than or equal to (>/=) 12 weeks
  -  Participant has not consumed tobacco or nicotine-containing products for 42 days prior to first dose of study drug, and must agree to refrain from such products while on study
  -  Adequate hematologic, renal and liver function
  Exclusion Criteria:
  -  Prior treatment with vemurafenib or other BRAF inhibitor within 42 days of Day 1
  -  History of or current clinically significant cardiac or pulmonary dysfunction, including current uncontrolled Grade >/= 2 hypertension or unstable angina
  -  Current dyspnea at rest due to complications of advanced malignancy or any requirement for supplemental oxygen
  -  Active central nervous system lesions (participants with radiographically unstable, symptomatic lesions)
  -  Participants with CYP1A2 gene mutation (-3113G->A), either in one or two alleles
  -  Allergy or hypersensitivity to vemurafenib or tizanidine formulations
  -  Current severe uncontrolled systemic disease
  -  Inability or unwillingness to swallow pills
  -  History of malabsorption or other condition that would interfere with enteral absorption of study treatment
  -  History of clinically significant liver disease (including cirrhosis), current alcohol abuse, or human immunodeficiency (HIV) infection requiring antiretroviral treatment, acquired immune deficiency syndrome (AIDS)-related illness, or active hepatitis B or C
  -  Pregnant or breastfeeding women

Relevance to patient case: not relevant
Patient case: 38-year-old male with melanoma; genetic feature: BRAF (K601E)

Clinical trial: Circulating Melanoma Cells in Metastatic Patients Treated With Selective BRAF Inhibitors

Summary: The purpose of this study, is to evaluate Circulating Melanoma Cell (CMC) changes in Metastatic Melanoma (MM) patients, undergoing treatment with selective inhibitors of mutated BRAF.

Detailed description: This is an observational prospective pilot study aimed to investigate the association between changes of total and apoptotic CMC count and disease progression in MM patients undergoing treatment with selective inhibitors of mutated B-RAF.

Eligibility: Inclusion Criteria:
  -  Fourth stage Melanoma patients with both measurable and not measurable lesions undergoing treatment with selective B-RAF inhibitors will be included. To determine the prevalence of CMC-positive patients in IV stage Melanoma, patients without mutated B-RAF undergoing chemotherapy and/or vaccines will be also enrolled at baseline, as part of study protocols approved and activated in the participating centers.
  -  Informed written consent.
  Exclusion Criteria:
  -  Inadequate compliance to multiple blood draws (baseline, 15 days, 1th month, 4th month, and/or at progression) as scheduled in this adjunctive biologic study for patients carrying B-FAF mutation; inadequate compliance to adjunctive blood draws, as scheduled at baseline for BRAF wild-type
  -  Previously exposure to immunological treatment.

Relevance to patient case: possibly relevant