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

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

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

Clinical trial: Differential Plasma MicroRNA Profiles in ED and Normal Erectile Function in Older Males

Summary: Erectile dysfunction (ED) is strongly associated with aging. With the rapidly expanding aging population and the increase in life expectancy, an increase in the prevalence of ED is expected in the years to come. Currently, the mechanism of ED is not fully understood. MicroRNAs (MiRNA) are endogenous small RNA molecules that control gene expression post-transcriptionally. It has been included in many in vitro physiology and pathophysiology processes, which also involved in the process of ED. This research was designed to investigate the differential plasma MiRNA profiles in ED and normal erectile function in older males. The results might tell us which MiRNA and how did it involved in the process of ED in aging.


Eligibility: Inclusion Criteria:
  -  older males with erectile dysfunction
  Exclusion Criteria:
  -  have some other general diseases, e.g. hypertension, vascular diseases, depression, chronic kidney disease, diabetes.

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

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

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

Clinical trial: Modified Melanoma Vaccine for High Risk or Low Residual Disease Patients

Summary: This study is designed for patients who had malignant melanoma and, following tumor removal, are now free of disease, or have only very minor residual disease, and are at a very high risk of disease recurrence. These patients will be treated with the A2/4-1BBL melanoma vaccine, a compatible melanoma cell line that has been engineered to express a molecule termed 4-1BBL, which enhances the chances of the cell line to be recognized by the patient's immune system, and to induce its stimulation. The hypothesis that drives the study states that the immune response against the cell line will also be effective against the residual tumor that may still be present in the body.


Eligibility: Inclusion Criteria:
  1. Patients included in this protocol must carry one or more of the following tissue typing alleles: HLA-A2, -A24, -A33, -B35, -B49, -CW04/12(04/08). We estimate that 50% of melanoma patients will be eligible.
  2. Cutaneous malignant melanoma AJCC stage IIb (>4 mm) or IIc (ulcerated melanoma >4mm).
  3. Metastatic melanoma AJCC stage III (nodal involvement, N1-3a,b) post-surgical removal of lymph nodes.
  4. Metastatic melanoma AJCC stage IV, completely resected.
  5. Non-resectable metastatic melanoma of low burden disease and normal LDH who have undergone at least two treatment lines, including chemotherapy (DTIC, temodal, taxanes, platinum compounds), anti-CTLA-4 (ipilimumab) and B-RAF inhibitor if harboring the V600E BRAF mutation in their tumor.
  6. Non cutaneous malignant melanoma of respective stages including uveal and mucosal melanoma.
  7. Melanoma can be of either mutant or wild-type B-RAF.
  8. Karnofsky performance status > 80 (Normal activity with effort).
  9. No active cardio-respiratory disease.
  10. Not pregnant or nursing. Women must take contraceptives during the treatment period.Hematocrit >25% and WBC >3000.
  11. Informed consent of the patient.
  Exclusion Criteria:
  1. Administration of cytotoxic drugs or extensive radiotherapy less than 28 days prior to protocol administration.
  2. Active brain metastases requiring corticosteroids.
  3. Concurrent malignancy (other than skin cancer, carcinoma in situ of cervix and early stage prostate cancer).
  4. Active serious infection.
  5. Allergy to penicillin.
  6. Patient's will to withdraw from the study at any stage.
  7. HIV and chronic hepatitis B and C carrier

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

Clinical trial: Bevacizumab Combined With Carboplatin Plus Paclitaxel Chemotherapy to Treat Metastatic Mucosal Melanoma

Summary: Mucosal melanoma is rare and associated with extremely poor prognosis.No effective treatment for advanced mucosal melanoma patients.Investigators conducted a randomized phase II study in patients with previously untreated metastatic mucosal melanoma to characterize the efficacy and safety of bevacizumab when combined with carboplatin plus paclitaxel.

Detailed description: Mucosal melanoma is rare and associated with extremely poor prognosis.It is the second most common subtype in Asians.No effective treatment for advanced mucosal melanoma patients.Malignant melanoma is a highly vascular tumor in which vascular endothelial growth factor(VEGF) is strongly expressed and seems to play an important role in disease progression.A randomized phase II study evaluated the activity of Bevacizumab in combination with carboplatin plus paclitaxel(CPB arm) in patients with previously untreated advanced melanoma.Overall response rates was 25.5%,median overall survival time(OS) was 12.3 months in the CPB arm. Investigators conducted a randomized phase II study in patients with previously untreated metastatic mucosal melanoma to characterize the efficacy and safety of bevacizumab when combined with carboplatin plus paclitaxel.

Eligibility: Inclusion Criteria:
  1. Histologically confirmed mucosal melanoma with metastases and has no received any systemic treatment.
  2. ECOG performance status 0, 1
  3. Estimated life expectancy of 12 weeks or greater
  4. Age 18 years or older, male or female
  5. At least one measurable site (diameter≥1cm) of disease (RECIST 1.1).
  6. Adequate organ function
  7. Without symptoms of brain metastases and stable in neuro-functions.
  8. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
  Exclusion Criteria:
  1. Mutations in C-KIT or BRAF-V600E, asked for other target treatments
  2. Pregnant or lactation women
  3. Acute infections without control.
  4. Heart disease history, cardiac function class≥NYHA II.
  5. HIV positive or chronic HBV/HCV in active stage.
  6. Brain metastases or primary tumor with positive symptoms
  7. Need anti-epileptic treatments
  8. Organ transplantation history
  9. Hemorrhagic tendency or related history
  10. Renal dialysis patients
  11. Diagnosis of any second malignancy within the last 3 years, except for adequately treated.
  12. Current treatment on another clinical trial
  13. The other improper situations which investigator judged.

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

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

Clinical trial: Lavage of the Uterine Cavity for the Diagnosis of Ovarian and Tubal Carcinoma and Their Premalignant Changes.

Summary: Epithelial Ovarian cancer (EOC) is the leading cause of death among gynaecologic malignancies in western civilized countries, with an estimated prevalence in Europe and the US of 752,600 in 2007 and 59,828 deaths annually.
  State-of-the-art diagnostic tests for EOC include transvaginal ultrasonography and serum cancer antigen (CA-125) measurements; the specificity of these diagnostic tools however is low, and both tests are not effective enough at detecting EOC early enough to improve clinical outcomes. Definitive diagnosis of EOC still relies on histological or cytological confirmation. These findings underline the importance for an effective test for early detection of EOC.
  In the current project we will obtain a lavage of the uterine cavity. It will be investigated whether cells from EOCs or genetic material from those cells can be detected in the lavage fluid.
  Aim of this study:
  There is a clear clinical need for a diagnosis test to detect EOC at an earlier stage.

Detailed description: Epithelial Ovarian cancer is the leading cause of death among gynaecologic malignancies in western civilized countries, with an estimated prevalence in Europe and the US of 752,600 in 2007 and 59,828 deaths annually. Treatment and survival of the patients depend primarily on the stage of the disease. Of all EOC patients only 25% are diagnosed at an early stage while the tumour is confined to the pelvis. In these cases the five-year survival rate is 80% to 90% and the disease can often be cured by the combination of surgery and chemotherapy. Unfortunately, almost 75% of women affected have advanced stage disease with metastatic spread throughout the abdominal cavity or to retroperitoneal lymph nodes at the time of diagnosis; five-year survival rates drop to 10%-30% for advanced disease, despite maximum surgical effort and combination chemotherapy.
  State-of-the-art diagnostic tests for EOC include transvaginal ultrasonography and serum cancer antigen (CA-125) measurements; the specificity of these diagnostic tools however is low, and both tests are not effective enough at detecting EOC early enough to improve clinical outcomes. Definitive diagnosis of EOC still relies on histological or cytological confirmation. These findings underline the importance for an effective test for early detection of EOC.
  In the current project we will obtain a lavage of the uterine cavity. It will be investigated whether cells from EOCs or genetic material from those cells can be detected in the lavage fluid.
  Aim of this study:
  There is a clear clinical need for a diagnosis test to detect EOC at an earlier stage.

Eligibility: Inclusion Criteria:
  -  suspected ovarian cancer
  -  verified ovarian cancer
  Exclusion Criteria:
  -  pregnant
  -  incapacitated persons

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

Clinical trial: Circulating Cell-free DNA in Metastatic Melanoma Patient: Mutational Analyses in Consecutive Measurement Before and After Chemotherapy

Summary: Therapies that target specific molecules markedly inhibit cancer growth in several malignancies, and provide valuable strategies for the treatment of advanced melanoma. In recent years, BRAF and KIT have become established therapeutic targets in melanoma patients showing activating mutations in these oncogenes. However, it is crucial that genetic mutations present in the melanoma lesions are identified if the investigators are to design tailormade therapies for individual patients. The tumour genotypes that determine the selection of molecular-targeted therapies are usually identified in primary tumours; however, primary tumours are not always representative of metastases. Circulating free DNA may be a source of valuable information because it can be obtained via routine blood sampling, it provides real-time information about a patient's current disease state, and it allows monitoring and molecular characterization before and after chemotherapy. The aim of the study is to determine the mutational status in circulating DNA in melanoma metastatic patients, with the Sequenom Mass Array, a next generation sequencing technology. Results obtained before and after treatment will be compared with the primary tumor genotype.


Eligibility: Inclusion Criteria:
  -  Age>18 years
  -  Surgical biopsy for histologic diagnostic
  -  All melanoma subtypes
  -  Known genotype BRAF V600
  -  Affiliation social security
  -  Consent form signed
  Exclusion Criteria:
  -  Patient with histories of cancer or the other synchronous cancer
  -  Pregnant women
  -  Breast-feeding women
  -  Vulnerable patients: major under guardianship; patient deprived of its rights

Relevance to patient case: possibly relevant