araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 54-year-old female with lung adenocarcinoma; genetic feature: SND1-BRAF fusion

Clinical trial: Study to Determine the Effectiveness of GSK1120212 in BRAF Mutation-positive Melanoma Previously Treated With or Without a BRAF Inhibitor

Summary: MEK113583 is a Phase II open-label, multi-site study to investigate the objective response rate, safety, and pharmacokinetics of GSK1120212 in subjects with BRAF mutation-positive melanoma who were previously treated with or without a BRAF inhibitor. GSK1120212 is a potent and highly selective inhibitor of MEK activation and kinase activity.


Eligibility: Inclusion Criteria:
  -  Metastatic cutaneous melanoma that was previously treated with: (Cohort A) a BRAF inhibitor either with or without other prior therapy. (Cohort B) at least 1 prior chemotherapy or immunotherapy, without treatment with a BRAF inhibitor.
  -  Documented positive BRAF mutation (V600E, V600K, or V600D).
  -  Subjects must provide archived tumor tissue or undergo fresh tumor biopsy prior to enrollment.
  -  The subject must have a radiographically measurable tumor.
  -  The subject is able to carry out daily life activities without significant difficulty (ECOG performance status score of 0 or 1).
  -  Able to swallow and retain oral medication.
  -  Sexually active subjects must use acceptable methods of contraception during the course of the study.
  -  Adequate organ system function and blood cell counts.
  Exclusion Criteria:
  -  The subject has had major surgery or received certain types of cancer therapy within 21 days before starting the study.
  -  Previous treatment with a MEK inhibitor.
  -  Current use of a prohibited medication listed in the protocol.
  -  Uncontrolled glaucoma.
  -  Brain metastasis, unless previously treated with surgery or stereotactic radiosurgery, and the disease has been stable for at least 2 months prior to enrollment.
  -  Current severe or uncontrolled systemic disease.
  -  History of clinically significant heart, lung, or eye/vision problems.
  -  Significant unresolved side effects from previous anti-cancer therapy.
  -  The subject is pregnant or breastfeeding.

Relevance to patient case: not relevant
Patient case: 54-year-old female with lung adenocarcinoma; genetic feature: SND1-BRAF fusion

Clinical trial: A Retrospective Study of Biomarkers in Non-Small Cell Lung Cancer

Summary: The purpose of this study is:
  1. To characterize the types and frequency of molecular alterations to the epidermal growth factor receptor (EGFR) pathway, FGFR4 and EML-ALK in Asian patients with non-small cell lung cancer
  2. To identify candidate biomarkers of importance in the EGFR and estrogen pathways
  Most, if not all, human malignancies including lung cancer are caused by somatic alterations of the genome, leading to activation of oncogenes or inactivation of tumor suppressor genes and their resultant oncogenic effects. In addition to mutations, increased chromosomal copy number (by amplification or polysomy) and DNA methylation are other mechanisms of oncogene activation and tumour suppressor gene inactivation respectively.
  Little is known about the relationship between these oncogenes of the EGFR family and the recently described oncogenes FGFR4 and fusion gene EML4-ALK. Recent data suggests molecularly defined subgroups of non-small cell lung cancer (NSCLC) exist and can be used to predict for sensitivity to targeted agents (erlotinib or gefitinib) or cytotoxic chemotherapy (pemetrexate, gemcitabine, platinum agents). The findings that estrogen receptors are present in lung tumours and that estrogen can stimulate growth and proliferation of lung cancers in vitro and in vivo are provocative. Further studies to evaluate the role of estrogens and other sex hormones in lung cancer are warranted.
  A further understanding of the molecular indicators of lung cancer prognosis and treatment prediction would improve drug development and patient treatment selection.
  Archived paraffin-embedded and fresh frozen NSCLC tumor tissue will be obtained via the Department of Pathology and the National University Tissue Repository respectively. Clinico-pathological characteristics will be obtained from the case records, Pathology and Tissue Repository. DNA will be isolated using standard techniques. Sequencing of genes in the EGFR signaling pathway: EGFR, KRAS, ErbB2, ErbB3, MET, PI3K, and BRAF as well as FGFR4. Unstained slides from the paraffin-embedded tissue will be obtained and subjected to fluoresce in vitro hybridization (FISH) for breakpoints in the EML4 and ALK genes as previously described. For cases that have been snap-frozen, RNA will be extracted and EML4-ALK fusions will be confirmed using RT-PCR and pre-specified primers. To analyse the expression of proteins of putative relevance to EGFR function (such as EGFR, ErbB2, ErbB3, AKT, MET, STAT, ERK, MAPK, cyclin D1, C/EBPa), downstream effects of EGFR: cell proliferation (Ki-67), angiogenesis (CD34, VEGF-A), apoptosis (bcl-2), metastasis, and hormonal influence (oestrogen and progesterone receptors, aromatase), TMA technology will be utilised. The status of the tumor suppressor genes PTEN and C/EBPa will be analysed.


Eligibility: Inclusion Criteria:
  -  Nil
  Exclusion Criteria:
  -  Nil

Relevance to patient case: not relevant
Patient case: 54-year-old female with lung adenocarcinoma; genetic feature: SND1-BRAF fusion

Clinical trial: Biomarkers in Blood Samples From Patients With Refractory Non-Small Cell Lung Cancer Previously Treated With Sorafenib Tosylate

Summary: RATIONALE: Studying samples of blood from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer.
  PURPOSE: This research study is studying biomarkers in blood samples from patients with refractory non-small cell lung cancer previously treated with sorafenib tosylate.

Detailed description: OBJECTIVES:
  -  To determine the mutation rates of BRAF, KRAS, and EGFR in patients with non-small cell lung cancer treated with sorafenib tosylate on protocol ECOG-2501.
  -  To determine the association between BRAF, KRAS, or EGFR mutation status and clinical benefits in patients treated with this regimen.
  OUTLINE: This is a multicenter study.
  DNA is isolated from archived plasma samples and analyzed for BRAF, KRAS, and EGFR mutations.

Eligibility: DISEASE CHARACTERISTICS:
  -  Diagnosis of refractory non-small cell lung cancer
  -  Received sorafenib tosylate on protocol ECOG-E2501
  -  Available blood specimens
  PATIENT CHARACTERISTICS:
  -  Not specified
  PRIOR CONCURRENT THERAPY:
  -  See Disease Characteristics

Relevance to patient case: possibly relevant
Patient case: 54-year-old female with lung adenocarcinoma; genetic feature: SND1-BRAF fusion

Clinical trial: A Study of RO5212054 (PLX3603) in Participants With BRAF V600-Mutated Advanced Solid Tumors

Summary: This open-label, multi-center study will evaluate the safety, tolerability, and pharmacokinetics of RO5212054 [PLX3603] in participants with BRAF V600-mutated advanced solid tumors. Cohorts of participants will receive escalating oral doses of RO5212054. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.


Eligibility: Inclusion Criteria:
  -  Advanced solid tumor
  -  Dose-escalation phase: Histologically confirmed, newly diagnosed or relapsed/ refractory unresectable American Joint Committee on Cancer (AJCC) Stage IIIC or IV disease
  -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  -  Adequate liver, renal and bone marrow function
  Exclusion Criteria:
  -  Participants for whom standard therapy exists and is considered appropriate by the investigator
  -  Prior treatment with an inhibitor of BRAF (sorafenib allowed)
  -  Active Central nervous system (CNS) lesions, or history of or known carcinomatous meningitis
  -  Treatment with any chemotherapy, radiotherapy, immunotherapy or investigational agent within 28 days prior to first dose of study drug
  -  Anticipated or ongoing anti-cancer therapies other than those administered in this study
  -  Serious cardiovascular illness within the 6 months prior to study drug administration

Relevance to patient case: possibly relevant
Patient case: 54-year-old female with lung adenocarcinoma; genetic feature: SND1-BRAF fusion

Clinical trial: A Study of GSK2118436 in BRAF Mutant Metastatic Melanoma

Summary: BRF113710 is a Phase II, single-arm, open-label study to assess the efficacy, safety, and tolerability of GSK2118436 administered twice daily as a single agent in subjects with BRAF mutant metastatic melanoma. Subjects will receive 150 mg of GSK2118436 twice daily and continue on treatment until disease progression, death, or unacceptable adverse event.


Eligibility: Inclusion Criteria:
  -  Must be at least 18 years of age
  -  Must have histologically confirmed cutaneous metastatic melanoma (Stage IV) that is BRAF mutation-positive (V600 E/K) as determined via central testing with a BRAF mutation assay.
  -  Is treatment naive or has received prior treatment for metastatic melanoma.
  -  Must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
  -  Women of child-bearing potential must have a negative pregnancy test within 14 days prior to the first dose of study treatment.
  -  Women with reproductive potential must be willing to practice acceptable methods of birth control during the study and for up to 4 weeks after the last dose of study medication.
  -  Men with reproductive potential must be willing to practice acceptable methods of birth control during the study and for up to 16 weeks after the last dose of study medication.
  -  Must have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
  -  Adequate organ function.
  Exclusion Criteria:
  -  Previous treatment with a BRAF or MEK inhibitor.
  -  Cancer therapy (chemotherapy with delayed toxicity, radiation therapy, immunotherapy, biologic therapy, or major surgery) within the last 3 weeks; chemotherapy regimens without delayed toxicity within the last 2 weeks; or use of any investigational anti-cancer or other drug within 28 days or 5 half-lives, whichever is longer, preceding the first dose of GSK2118436.
  -  A history of known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection.
  -  History or evidence of brain metastases on MRI or head CT if MRI is not able to be performed.
  -  History of other malignancy. Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
  -  Certain cardiac abnormalities.

Relevance to patient case: not relevant
Patient case: 54-year-old female with lung adenocarcinoma; genetic feature: SND1-BRAF fusion

Clinical trial: A Clinical Trial Testing The Efficacy Of Crizotinib Versus Standard Chemotherapy Pemetrexed Plus Cisplatin Or Carboplatin In Patients With ALK Positive Non Squamous Cancer Of The Lung

Summary: This study will evaluate the anti-cancer effects of crizotinib when compared with standard chemotherapy in patients with ALK positive lung cancer.


Eligibility: Inclusion Criteria:
  -  Proven diagnosis of locally advanced not suitable for local treatment, recurrent and metastatic non-squamous cell carcinoma of the lung
  -  Positive for translocation or inversion events involving the ALK gene locus
  -  No prior systemic treatment for locally advanced or metastatic disease; Patients with brain metastases only if treated and neurologically stable with no ongoing requirement for corticosteroids
  -  Evidence of a personally signed and dated informed consent document and willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures including completion of patient reported outcome [PRO] measures.
  -  18 years of age or older with the exception of India which has an upper age limit of 65 years old
  Exclusion Criteria:
  -  Current treatment on another therapeutic clinical trial.
  -  Prior therapy directly targeting ALK.
  -  Any of the following within the 3 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, or cerebrovascular accident including transient ischemic attack. - - Appropriate treatment with anticoagulants is permitted.
  -  Ongoing cardiac dysrhythmias of NCI CTCAE Grade >=2, uncontrolled atrial fibrillation of any grade, or QTc interval >470 msec.
  -  Pregnancy or breastfeeding.
  -  Use of drugs or foods that are known potent CYP3A4 inducers/inhibitors Concurrent use of drugs that are CYP3A4 substrates with narrow therapeutic indices.
  -  Known HIV infection
  -  Known interstitial lung disease or interstitial fibrosis
  -  Other severe acute or chronic medical conditions (including severe gastrointestinal conditions such as diarrhea or ulcer) or psychiatric conditions, or laboratory abnormalities that would impart, in the judgment of the investigator and/or sponsor, excess risk associated with study participation or study drug administration, and which would, therefore, make the patient inappropriate for entry into this study

Relevance to patient case: not relevant
Patient case: 54-year-old female with lung adenocarcinoma; genetic feature: SND1-BRAF fusion

Clinical trial: A Study to Investigate Safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) of BKM120 Plus GSK1120212 in Selected Advanced Solid Tumor Patients

Summary: This is an open label, dose finding, phase Ib clinical trial to determine the maximum tolerated dose (MTD) and /or recommended phase II dose (RP2D) and schedule for the PI3K (Phosphatidylinositol 3-Kinase) inhibitor BKM120 given in combination with the MEK inhibitor GSK1120212 in patients with selected, advanced solid tumors. The focus will be on tumors with RAS/RAF mutations and on triple negative breast cancer.
  Both study drugs will be administered once daily orally on a continuous schedule, a treatment cycle is defined as 28 days.
  Cohorts of at least 3 and up to a maximum of 6 patients eligible for the dose-determining set will be enrolled per dose combination below the MTD. The MTD is defined as the highest drug dosage not causing in the first cycle of treatment medically unacceptable, dose-limiting toxicity (DLT) in more than 33% of the treated patients.. At least 12 patients will be required at MTD and 6 patients at RP2D level to allow the evaluation of the combination's safety and pharmacokinetics or pharmacodynamics.
  Upon declaration of MTD and/or RP2D, patients will be enrolled to an expansion part of the study, to further assess safety, as well as to learn more about the efficacy of the study drug combination.
  -  Expansion Arm 1 will consist of approximately 15 patients with RAS or BRAF mutant advanced NSCLC
  -  Expansion Arm 2 will consist of approximately 15 patients with RAS or BRAF-mutant ovarian cancer
  -  Expansion Arm 3 will consist of approximately 15 patients with RAS or BRAF-mutant pancreatic cancer


Eligibility: Inclusion Criteria:
  -  histologically/ cytologically confirmed, advanced non resectable solid tumors
  -  Measurable or non-measurable, but evaluable disease as determined by RECIST 1.0
  Exclusion Criteria:
  -  Patients with primary Central Nervous System (CNS) tumor or CNS tumor involvement.
  -  Clinically manifested diabetes mellitus - Unacceptable ocular/retinal conditions
  Other protocol-defined inclusion/exclusion criteria may apply.

Relevance to patient case: possibly relevant
Patient case: 54-year-old female with lung adenocarcinoma; genetic feature: SND1-BRAF fusion

Clinical trial: A Study Comparing GSK2118436 to Dacarbazine (DTIC) in Previously Untreated Subjects With BRAF Mutation Positive Advanced (Stage III) or Metastatic (Stage IV) Melanoma

Summary: BRF113683 is a Phase III, randomized, open-label study comparing the efficacy, safety, and tolerability of GSK2118436 to dacarbazine (DTIC), in subjects with BRAF mutant advanced (Stage III) or metastatic (Stage IV) melanoma. Subjects will be randomized to receive 150 mg of GSK2118436 twice daily or 1000 mg/m2 DTIC every 3 weeks and continue on treatment until disease progression, death, or unacceptable adverse event. Subjects who progress on DTIC will be allowed to crossover to an optional extension arm of the study to receive GSK2118436.


Eligibility: Inclusion Criteria:
  -  Adults at least 18 years of age
  -  Has advanced (unresectable Stage III) or metastatic (Stage IV) melanoma that is BRAF mutation positive (V600E)
  -  Is treatment naive for advanced (unresectable) or metastatic melanoma, with the exception of Interleukin 2 (IL-2) which is allowed.
  -  Has measurable disease according to RECIST 1.1 criteria.
  -  Women of child-bearing potential must have a negative pregnancy test within 14 days prior to the first dose of study treatment.
  -  Women with reproductive potential must be willing to practice acceptable methods of birth control during the study and for up to 4 weeks after the last dose of study medication.
  -  Men with reproductive potential must be willing to practice acceptable methods of birth control during the study and for up to 16 weeks after the last dose of study medication.
  -  Must have adequate organ function.
  -  Must have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
  Exclusion Criteria:
  -  Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy or surgery).
  -  Evidence of active central nervous system (CNS) disease.
  -  Previous treatment for metastatic melanoma, including treatment with BRAF or MEK inhibitor.
  -  A history of other malignancy. Subjects who have been disease-free for 5 years or subjects with a history of complete resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
  -  History of Human Immunodeficiency Virus (HIV) infection.
  -  Certain cardiac abnormalities

Relevance to patient case: not relevant
Patient case: 54-year-old female with lung adenocarcinoma; genetic feature: SND1-BRAF fusion

Clinical trial: Biomarkers in Predicting Response to Cetuximab in Patients With Advanced Colorectal Cancer

Summary: RATIONALE: Studying samples of tissue in the laboratory from patients who received cetuximab may help doctors understand and predict how well patients will respond to treatment.
  PURPOSE: This research study is studying biomarkers in predicting response to cetuximab in patients with advanced colorectal cancer.

Detailed description: OBJECTIVES:
  Primary
  -  To determine, among patients with advanced CRC, whether the effect of treatment (cetuximab vs bevacizumab) on progression-free survival (PFS) depends on tumor BRAF V600E mutational status.
  Secondary
  -  To study the relationships between tumor BRAF V600E mutational status, OS, and tumor response.
  OUTLINE: This is a multicenter study.
  Previously collected formalin-fixed and paraffin-embedded baseline tumor samples are analyzed for BRAF V600E mutation. Mutation status is correlated with clinical response and outcome data from patients enrolled on CALGB-C80405.

Eligibility: DISEASE CHARACTERISTICS:
  -  Participation in CALGB-C80405
  -  Have KRAS WT or KRAS mut tumor
  -  Randomized to treatment with either bevacizumab or cetuximab alone
  -  Patients randomized to the combination therapy are not eligible
  -  Available specimens at the PCO for BRAF mutation detection
  -  Patient consent for use of samples

Relevance to patient case: not relevant
Patient case: 54-year-old female with lung adenocarcinoma; genetic feature: SND1-BRAF fusion

Clinical trial: Expression of Optic Atrophy Type 1 (OPA1) Protein in Lung Adenocarcinoma

Summary: Optic atrophy type 1(OPA1) is a nuclear dynamin-related GTPase, targeted to the inner mitochondrial membrane, which plays a role in mitochondrial fusion. Mitochondria fusion is associated with process of apoptosis. . OPA1 plays an important role in the mitochondrial bioenergetics and mitochondrial networks. The changes in mitochondrial shape and mitochondrial bioenergetics may be cause of the disease. In this study, we investigate the expression of OPA1 in lung adenocarcinoma (LADC) cells and tissue.


Eligibility: Inclusion Criteria:
  -  We will collect paraffin blocked resected lung tissue samples from stage I~IIIa non-small cell lung cancer patients (age, 40~80 years old) who received lobectomy of the affected lung.
  Exclusion Criteria:
  -  History of uremia, other malignant disease, and liver cirrhosis
  -  History of pneumonia and pulmonary tuberculosis
  -  History of long period of medications.

Relevance to patient case: not relevant
Patient case: 54-year-old female with lung adenocarcinoma; genetic feature: SND1-BRAF fusion

Clinical trial: A Study of the Effect of Food on the Pharmacokinetics of Single Dose RO5185426 And the Safety And Efficacy of Continuous Administration in Patients With BRAF V600E Mutation-Positive Metastatic Melanoma

Summary: This randomized, open-label, two period crossover study will evaluate the effect of food on the pharmacokinetics of a single dose of RO5185426 and the efficacy and safety of continuous administration in patients with BRAF V600E mutation-positive metastatic melanoma. Patients will be randomized to receive in a crossover design single oral doses of RO5185426 with or without food, with a 10-day washout period between doses. Following the crossover periods, patients will receive RO5185426 orally twice daily on a continuous basis until disease progression or unacceptable toxicity occurs.


Eligibility: Inclusion Criteria:
  -  Adult patients, >/= 18 years of age
  -  Histologically confirmed metastatic melanoma (Stage IV, American Joint Committee on Cancer)
  -  Positive BRAF V600E mutation result determined by Cobas 4800 BRAF V600 Mutation Test
  -  Previously treated patients must have failed at least one prior treatment regimen; if patients have received prior systemic treatments for metastatic melanoma, the time elapsed from previous therapy must be >/= 28 days; patients must have recovered fully from toxicities of all prior therapy
  -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  -  Evaluable disease (measurable for disease progression according to RECIST criteria)
  -  Adequate hematological, renal and liver function
  Exclusion Criteria:
  -  Active 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 BRAF inhibitor (sorafenib allowed) or MEK inhibitor
  -  Refractory nausea or vomiting, malabsorption, external biliary shunt, or history of any type of gastrointestinal surgery that would preclude adequate absorption of study drug

Relevance to patient case: not relevant