araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 82-year-old male with glioma; genetic feature: BRAF

Clinical trial: A Study of GDC-0084 in Patients With Progressive or Recurrent High-Grade Glioma

Summary: This open-label, multicenter, Phase I, dose-escalating study will evaluate the safety and tolerability, pharmacokinetics, pharmacodynamics and efficacy of GDC-0084 in patients with progressive or recurrent high-grade glioma. Stage 1 is the dose escalation part of the study. Stage 2, patients will receive GDC-0084 at a recommended dose for future studies.


Eligibility: Inclusion Criteria:
  -  Adult patients, >/= 18 years of age
  -  Interval of at least 12 weeks from completion of adjuvant radiotherapy for gliomas to study entry
  -  Karnofsky Performance Status of >/= 70 at screening
  -  Confirmed measurable disease per RANO
  -  Adequate hematologic and organ function
  Patients enrolled in Stage 1:
  -  Histologically documented recurrent or progressive high-grade gliomas (WHO Grade III-IV)
  -  Prior treatment with at least one regimen for gliomas (radiotherapy with or without chemotherapy for Grade III gliomas and radiotherapy with chemotherapy for Grade IV gliomas) and/or not considered to be a candidate for regimens known to provide clinical benefit
  Patients enrolled in Stage 2:
  -  Histologically documented recurrent or progressive glioblastoma (WHO Grade IV gliomas)
  -  Prior treatment with one or two regimens for glioblastoma (with the initial regimen consisting of radiotherapy with chemotherapy)
  Exclusion Criteria:
  -  Treatment with anti-tumor therapy (approved or experimental) within 4 weeks prior to initiation of study drug
  -  Requirement for anticoagulants such as warfarin or any other warfarin-derivative anticoagulants; low-molecular-weight heparin is permitted
  -  Any contraindication to MRI examination
  -  Evidence of Grade >/= 1 intracranial hemorrhage
  -  Active congestive heart failure or ventricular arrhythmia requiring medication
  -  Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse or cirrhosis
  -  Unresolved toxicity from prior therapy with the exception of lymphopenia (for patients with prior temozolomide) and alopecia
  -  Pregnant or lactating women

Relevance to patient case: not relevant
Patient case: 82-year-old male with glioma; genetic feature: BRAF

Clinical trial: Imaging Study of Glioblastomas Treated With Avastin

Summary: This study aims to assess the effect of Avastin on brain vascularity and blood-brain permeability using dynamic contrast ct scans (DECT) and MRI imaging. Previous publications have documented the method by which DECT can determine alterations in vascular volume and tissue permeability within tumors and normal brain tissue. Functional maps of cerebral blood flow cerebral blood volume and permeability-surface area can be generated from the DECT studies to assess tumor perfusion. MRI spectroscopy analyzes brain chemistry to detect tumour versus edema versus normal brain. Thirty patients will receive MRI spectroscopy and DECT imaging at the time of presumed recurrence and 3 months later. 15 patients who do not receive Avastin and 15 patients who do receive Avastin as standard treatment for recurrence will be studied with DECT and MRI spectroscopy at baseline and then again in 3 months.

Detailed description: The clinical determination of the point of tumour progression or response is difficult to determine using standard diagnostic imaging ie CT/MRI especially following previous treatment with surgery, radiation and chemotherapy. Hemorrhage, edema, inflammation and vascular necrosis.
  Both MR spectroscopy and DECT have been reported as being able to define areas of recurrent tumour as opposed to treatment-related effects. We wish to investigate the correlation between MR spectroscopy and DECT in assessing tumour progression or response to Avastin in comparison with patients not receiving Avastin.
  Health Canada has approved Avastin for clinical use in patients with recurrent glioblastoma who have previously received temozolomide and radiotherapy. We propose to perform a DECT scan at baseline at presumed tumour progression and again 3 months to determine the effects of tumour progression/response on blood brain barrier permeability and vascular volume. The group of 15 patients will be compared to a group of 15 patients who do not receive Avastin at recurrence involving DECT scanning and MR spectroscopy at the time of the radiological progression and 3 months later.

Eligibility: Inclusion Criteria:
  -  Histological diagnosis of glioblastoma with clinical or radiological evidence of progression as indicated by the RANO criteria 19
  -  Previous radiation and temozolomide chemotherapy
  -  Patients must be receiving Avastin chemotherapy as second-line treatment if in the Avastin group
  -  Study-specific consent
  Exclusion Criteria:
  -  Failure to meet inclusion criteria
  -  Pregnant or lactating patients
  -  Allergy to iodine or CT contrast precludes DECT component of study
  -  Claustrophobia precludes MR Spectroscopy component of study
  -  Internal metal which would preclude an MRI scan

Relevance to patient case: not relevant
Patient case: 82-year-old male with glioma; genetic feature: BRAF

Clinical trial: A Study of MEK162 and AMG 479 in Patients With Selected Solid Tumors

Summary: This is a multi-center, open-label, phase Ib/II study. First, the aim of the phase Ib part is to estimate the MTD(s) and/or to identify the recommended phase II dose(s) (RP2D) for the combination of MEK162 and AMG 479 (ganitumab), followed by the phase II part to assess the clinical efficacy and to further assess the safety of the combination in selected patient populations. The dose escalation part of the study will be guided by a Bayesian Logistic Regression Model (BLRM). At least 18 patients are expected to be enrolled in the dose escalation part.
  Following MTD/ RP2D declaration, patients will be enrolled in three phase II arms to assess efficacy of the combination as well as to better understand the safety, tolerability, PK, antibody concentrations and PD of the combination at MTD/RP2D. Phase II arm 1 will consist of approximately 25 patients with KRAS-mutant colorectal adenocarcinoma. Phase II arm 2 will consist of approximately 20 patients with metastatic pancreatic adenocarcinoma. Phase II arm 3 will consist of approximately 28 patients with mutant BRAFV600 melanoma.
  Patients will be treated until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurs first. All patients will be followed up - at minimum patients must complete the safety follow-up assessments 30 days after the last dose of the study treatment.


Eligibility: Inclusion Criteria:
  -  Patients aged ≥ 18 years
  -  Patients with advanced solid tumors (CRC, melanoma) with documented somatic KRAS or BRAFV600 mutations in tumor tissue. Patients with metastatic pancreatic adenocarcinoma may be enrolled irrespectively of KRAS or BRAFV600 mutational status.
  -  Patients must have relapsed or progressed following standard therapy or patients for whom no standard anticancer therapy exists.
  -  Measurable disease as determined by RECIST v1.1. World Health Organization (WHO) Performance Status (PS) ≤ 2.
  -  Adequate organ function
  -  Negative serum pregnancy test
  Exclusion Criteria:
  -  Prior therapy with MEK- or IGF-1R- inhibitor
  -  History or current evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO) or retinal degenerative disease
  -  Patients with known history of severe infusion reactions to monoclonal antibodies
  -  Patients with primary CNS tumor or CNS tumor involvement
  -  History of thromboembolic event requiring full-dose anticoagulation therapy
  -  Clinically significant cardiac disease
  -  History of another malignancy within 2 years
  -  Pregnant or nursing (lactating) women
  Other protocol-defined inclusion/exclusion criteria may apply

Relevance to patient case: not relevant
Patient case: 82-year-old male with glioma; genetic feature: BRAF

Clinical trial: A Phase I Study to Investigate the Safety, Tolerability and Pharmacokinetic Profile of of GSK2118436 in Japanese Subjects With BRAF Mutation Positive Solid Tumors

Summary: BRF116056 is the first clinical experience with GSK2118436, a BRAF inhibitor, in Japan. This study will be designed to assess safety, tolerability, single and repeat dose PK profile and preliminary efficacy of GSK2118436 in Japanese subjects with BRAF V600 mutation positive solid tumors using continuous daily dosing schedule.

Detailed description: BRF116056 is the first clinical experience with GSK2118436, a BRAF inhibitor, in Japan. This study will be designed to assess safety, tolerability, single and repeat dose PK profile and preliminary efficacy of GSK2118436 in Japanese subjects with BRAF V600 mutation positive solid tumors using continuous daily dosing schedule. Dose escalation of GSK2118436 will be performed according to a standard 3+3 dose-escalation design. GSK2118436 is given twice a day. However, to characterize the PK of GSK2118436 and its metabolites after single-dose administration, GSK2118436 will NOT be administrated for a week after the first administration. GSK2118436 continuous dosing will start after the 168-hour PK sample is obtained. Subjects may receive study treatment until disease progression, death or an unacceptable adverse event.

Eligibility: Inclusion Criteria:
  -  Histologically or cytologically confirmed diagnosis of a solid tumor that is not responsive to standard therapies or for which there is no approved or curative therapy.
  -  Subjects must have BRAF V600E or K mutant positive tumors.
  -  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).
  -  Use of an investigational anti-cancer drug within 28 days preceding the first dose of GSK2118436.
  -  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.
  -  Pregnant or lactating female.

Relevance to patient case: not relevant
Patient case: 82-year-old male with glioma; genetic feature: BRAF

Clinical trial: Mutation Analysis and Copy Number Changes of KRAS and BRAF Gene in Taiwanese Cases of Biliary Tact Adenocarcinoma

Summary: Cholangiocarcinoma is a fatal malignant neoplasm originating from biliary tracts and constitutes about 5-10% of primary liver cancers, characterized by a poor prognosis. High prevalence in southeast and eastern Asia has been observed. At present, the cellular and molecular mechanisms leading to oncogenesis of cholangiocarcinoma remain unclear.
  The RAS gene product has a key role in controlling cell growth and differentiation through its intrinsic GTPase activity. Point mutations that activate the RAS protein and its downstream cascade have been observed in human tumors. Both KRAS and BRAF are members of the RAS-RAF-MEK-ERK-MAP kinase pathway which mediates cellular response to growth signals. Somatic KRAS mutations are found at high rates in leukemia, colon cancer, pancreatic cancer and lung cancer. Studies from European and Japanese groups have recently described that activating KRAS/ BRAF mutations may play a role in the carcinogenesis of cholangiocarcinoma of the biliary tracts, but our preliminary data demonstrated low frequency of KRAS and BRAF mutation in the same tumor as well as the results from Thailand. In this study, the investigators hypothesize copy number changes rather than genetic mutation of either KRAS or BRAF genes may be the key findings of Taiwanese cases of the adenocarcinoma from the biliary tracts.


Eligibility: Inclusion Criteria:
  -  The patients diagnosed as biliary tact adenocarcinoma.

Relevance to patient case: possibly relevant
Patient case: 82-year-old male with glioma; genetic feature: BRAF

Clinical trial: Experiences and Needs of Patients With a High-grade Glioma and Their Caregivers

Summary: The purpose of this study is to explore the experiences and needs of patients with a high-grade glioma and their caregivers. Semi-structured interviews with patients and caregivers will be conducted and analysed using Grounded-Theory approach.


Eligibility: Inclusion Criteria:
  -  Adults
  -  Patients with a primary high-grade glioma who are treated with chemo or were treated with chemo
  -  Caregivers of patients with a primary high-grade glioma who are treated with chemo or were treated with chemo
  -  Able to be interviewed
  -  Dutch
  Exclusion Criteria:
  -  Patients with cerebral metastases
  -  Patients and caregivers who withdraw their informed consent
  -  Emotionally and cognitive not being able to be interviewed

Relevance to patient case: not relevant
Patient case: 82-year-old male with glioma; genetic feature: BRAF

Clinical trial: Study of LGX818 and Cetuximab or LGX818, BYL719, and Cetuximab in BRAF Mutant Metastatic Colorectal Cancer

Summary: This study will assess the safety and efficacy of LGX818 when combined with cetuximab or combined with cetuximab and BYL719 in patients with BRAF mutant metastatic colorectal cancer


Eligibility: Inclusion Criteria:
  -  Metastatic colorectal cancer
  -  Progression after at least one prior standard of care regimen or be intolerant to irinotecan-based regimens
  -  Life expectancy ≥ 3 months
  -  ECOG performance status ≤ 2
  Exclusion Criteria:
  -  Symptomatic or untreated leptomeningeal disease
  -  Symptomatic brain metastasis
  -  Patients with clinically manifested diabetes
  -  Acute or chronic pancreatitis
  -  Clinically significant cardiac disease
  Other protocol-defined inclusion/exclusion criteria may apply.

Relevance to patient case: possibly relevant
Patient case: 82-year-old male with glioma; genetic feature: BRAF

Clinical trial: An Extension (Rollover) Study of Vemurafenib in Participants With BRAF V600 Mutation-Positive Malignancies Previously Enrolled in an Antecedent Vemurafenib Protocol

Summary: This open-label, multicenter, non-randomized study will provide continued access to vemurafenib for eligible participants with BRAF V600 mutation-positive malignancy, who were previously enrolled and treated in an antecedent vemurafenib protocol and did not meet the protocol's criteria for disease progression, or are treated beyond progression and are still deriving clinical benefit (as assessed by investigator), and may therefore potentially benefit from continued treatment with vemurafenib. Participants will receive treatment with oral vemurafenib at 960 milligrams (mg) twice daily (BID), 720 mg BID, or 480 mg BID, depending on the last dose in the antecedent protocol. Treatment will continue until progression of disease or as long as the participant is deriving clinical benefit, as judged by the investigator (case-by-case decision with approval of the Medical Monitor), death, withdrawal of consent, unacceptable toxicity, loss to follow-up, or decision of the Sponsor to terminate the study, whichever occurs first.


Eligibility: Inclusion Criteria:
  -  BRAF V600 mutation-positive malignancy
  -  Prior eligibility for and on study treatment from an antecedent vemurafenib protocol
  -  Ability to begin treatment in the extension (rollover) protocol within 15 days following the last day of the study in the antecedent protocol
  -  Female participants of childbearing potential and male participants with partners of childbearing potential must agree to use 2 adequate methods of contraception as defined by protocol during the course of this study and for at least 6 months after completion of study treatment
  Exclusion Criteria:
  -  Adverse event requiring discontinuation of vemurafenib in the antecedent protocol
  -  Progressive disease during the antecedent protocol. If approval to treat beyond progression was already given in the antecedent protocol, the participant may roll over into the current protocol without sponsor approval. Under special circumstances, enrollment into this protocol and dosing beyond progression may be considered and will require approval of the sponsor
  Participants meeting any of the following exclusion criterion of the antecedent study at the time the participant is considered for the extension (rollover) study:
  -  Current, recent (within 28 days prior to Day 1), or planned use of any antitumor therapy outside this study
  -  Any other serious concomitant medical condition that, in the opinion of the investigator, would compromise the safety of the participant or compromise the participant's ability to participate in the study
  -  History of malabsorption or other clinically significant metabolic dysfunction
  -  History of clinically significant cardiac or pulmonary dysfunction as specified in antecedent study

Relevance to patient case: possibly relevant
Patient case: 82-year-old male with glioma; genetic feature: BRAF

Clinical trial: Comparison of In-House Methods and Cobas BRAF V600 Mutation Assay in Melanoma Tumor Samples

Summary: This non-interventional study will compare the Cobas BRAF V600 mutation assay with in-house methods used in molecular laboratories for the assessment of the BRAF mutation status in melanoma tumor samples. No patients will be enrolled in this study. Data will be collected for approximately 6 months.


Eligibility: Inclusion Criteria:
  No patients are enrolled. Use of tumor samples only.
  -  Histologically proven melanoma tumor sample
  -  Any type of tumor sample: biopsy or surgical specimen of primary tumor or metastasis
  -  Tumor samples must be fixed and paraffin-embedded.
  Exclusion Criteria:
  No patients are enrolled. Use of tumor samples only.
  -  Fixative unknown

Relevance to patient case: not relevant
Patient case: 82-year-old male with glioma; genetic feature: BRAF

Clinical trial: A Phase III Trial on Adjuvant Temozolomide With or Without Interferon-alpha in Newly Diagnosed High-grade Gliomas

Summary: This study is being conducted to help determine whether the addition of Interferon-alpha(α-IFN),which were determined sensitized the activity of Temozolomide(TMZ) in vivo and vitro, when given along with temozolomide during the monthly cycles that follow radiation, is able to delay tumor growth, shrink tumors, or impact how long people with newly diagnosed high-grade glioma.

Detailed description: This study is being conducted to help determine whether the addition of Interferon-alpha(α-IFN),which were determined sensitized the activity of Temozolomide(TMZ) in vivo and vitro, when given along with temozolomide during the monthly cycles that follow radiation, is able to delay tumor growth, shrink tumors, or impact how long people with newly diagnosed high-grade glioma. Four weeks after radiotherapy, newly diagnosed WHO III-IV glioma patients will be randomised into two groups: TMZ group or TMZ+ α-IFN groups.

Eligibility: Inclusion Criteria:
  -  Age: 18 years to 75 years
  -  newly diagnosed WHO III-IV glioma after operation and radiotherapy
  -  Karnofsky Performance Score ≥ 60
  -  Adequate bone marrow, liver and renal function
  -  Ability of subject to understand character and individual consequences of the clinical trial
  -  Written informed consent
  -  anticipating survival ≥2 months
  Exclusion Criteria:
  -  Refusal to participate the study
  -  Known hypersensitivity or contraindication to temozolomide
  -  Incompletely radiation
  -  Pregnant or lactating females
  -  Malignant tumor other than brain tumor
  -  Contraindicated for MRI examination
  -  Unable to comply with the follow-up studies of this trial
  -  Purulent and chronic infected wounds
  -  Uncontrolled psychotic disorders or epilepsy

Relevance to patient case: not relevant
Patient case: 82-year-old male with glioma; genetic feature: BRAF

Clinical trial: A Study of The Impact of Severe Hepatic Impairment on the Pharmacokinetics and Safety of Vemurafenib in BRAF V600 Mutation-Positive Cancer Patients

Summary: This open-label, Phase I study will evaluate the impact of severe hepatic impairment on the pharmacokinetics and safety of vemurafenib in patients with BRAF V600 mutation positive cancer. Patients will receive vemurafenib 960 mg (normal hepatic function) or 720 mg (severe hepatic impairment) orally twice daily on Days 1 to 20 (morning dose) and from Day 27 onwards until disease progression or inacceptable toxicity occurs.


Eligibility: Inclusion Criteria:
  -  Adult patients, >/= 18 years of age
  -  Histologically confirmed BRAF V600 mutation-positive advanced solid malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
  -  Normal or impaired hepatic function (hepatic function will be classified according to the NCI Organ Dysfunction Working Group criteria)
  -  For patients with hepatic impairment: Stable hepatic function for at least 2 weeks before Day 1
  -  Eastern Cooperative Oncology Group (ECOG) performance status of </=2
  -  Patients with a history of recent brain metastases must have completed any radiation therapy at least 4 weeks before Day 1, be without intervening signs of brain lesion progression and not require steroids before starting the protocol (Day 1). Patients with gliomas or known brain metastases who require anticonvulsants must be seizure free for 1 month prior to enrollment
  -  Life expectancy > 8 weeks
  -  Adequate hematologic and renal function
  -  Females patients of childbearing potential and male patients with female partners of childbearing potential must agree to use two adequate methods of contraception as defined by protocol during the course of this study and for at least 6 months after completion of study treatment
  Exclusion Criteria:
  -  Allergy or hypersensitivity to components of the vemurafenib formulation
  -  Requirement for immediate or urgent treatment with vemurafenib and for whom the intermittent schedule of vemurafenib employed during Days 1-26 in this trial is not clinically acceptable
  -  Chemotherapy, biologic therapy, immunotherapy, or radiotherapy within 4 weeks prior to entering the study, or those who have not recovered from AEs because of agents administered more than 4 weeks earlier
  -  Gliomas or known brain metastases that require corticosteroids
  -  History of clinically significant cardiac or pulmonary dysfunction
  -  HIV-positive patient requiring antiviral treatment including protease inhibitors
  -  Active infection or chronic infection requiring chronic suppressive antibiotics
  -  Pregnancy or breastfeeding at Day 1
  -  History of malabsorption or other clinically significant metabolic dysfunction
  -  Active autoimmune disease
  -  Current, recent (within 28 days prior to Day 1), or planned use of any investigational product outside this study

Relevance to patient case: possibly relevant