araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 62-year-old male with cholangiocarcinoma; genetic feature: PIK3CA (1047H)

Clinical trial: Intra-hepatic Chemotherapy in Patient With Non-resectable Liver Metastases From Cholangiocarcinoma

Summary: A phase II trial evaluating intra-hepatic chemotherapy with oxaliplatin every second week in combination with systemic gemcitabine and capecitabine in combination with cetuximab in patient with non-resectable liver metastases from cholangiocarcinoma.


Eligibility: Inclusion Criteria:• Informed consent
  -  Age > 18 years
  -  Performance status 0-1; expected survival ≥ 3 months
  -  Patient with histologically or cytologically adenocarcinoma developed from cells in the gall bladder, extra- or intrahepatic bile ducts or malignant cells consistent with above mentioned and radiologic findings consistent with cholangiocarcinoma
  -  Liver metastases not suitable for surgery or other local treatment
  -  Extrahepatic disease should be excluded by PET-CT-scan.
  -  Prior treatment with chemotherapy or no progression on first line treatment
  -  Metastases < 70 % of the liver
  -  neutrophile granulocytes ≥ 1.5 x 109/l og thrombocytes ≥ 100 x 109/l
  -  bilirubin < 2.0 x UNL (upper normal limit).
  -  creatinine-clearance ≥ 30 ml/min.
  -  INR < 2.
  -  Intrahepatic treatment can be accomplished
  -  The patients is approved by a multidisciplinary team
  Exclusion Criteria:• Other current or prior malignant disease except adequately treated and cured carcinoma in situ of the cervix or squamous cell carcinoma of the skin.
  -  Cytotoxic or experimental treatment within a 14 days period before start of trial medication
  -  The patient is not allowed to participate in other clinical trials.
  -  Any clinical symptoms suggesting peripheral neuropathy grade 2
  -  Other severe medical conditions
  -  Severe cardial disease or AMI < 1 year
  -  Presence of diseases preventing oral therapy
  -  Patients with uncontrolled infection
  -  Pregnant or lactating women
  -  Women capable of childbearing not using a sufficient method of birth control
  -  Patients not able to understand the treatment or to collaborate
  -  Prior serious or unsuspected reaction after treatment with fluoropyrimidine
  -  Known prior hypersensitivity reactions to the agents
  -  Interstitial pneumonitis or pulmonary fibrosis

Relevance to patient case: not relevant
Patient case: 62-year-old male with cholangiocarcinoma; genetic feature: PIK3CA (1047H)

Clinical trial: BEZ235 Trial in Patients With HER2-(Human Epidermal Growth Factor Receptor 2 Negative) /HR+ (Hormonal Receptor Positive) Metastatic Breast Cancer

Summary: This is a prospective, multi-center, open-label, single arm, phase II study with a 2-stage design and Bayesian interim monitoring to investigate the safety and efficacy of BEZ235 in patients with progressive metastatic HR+ HER2- breast cancer who have received at least one prior line of endocrine therapy and two to three prior lines of chemotherapy for metastatic disease. Patients will be stratified into 3 groups according to their PI3K (phosphatidylinositol 3-Kinase) pathway activation status.


Eligibility: Inclusion Criteria:
  -  Female ≥ 18 years
  -  ECOG performance status ≤ 2
  -  Histologically and/or cytologically confirmed diagnosis of breast cancer presenting with metastatic disease (hormone receptor positive and HER2 negative)
  -  Known PI3K activation status (defined by PIK3CA (Phosphoinositide-3-kinase, catalytic, alpha polypeptide) mutation and PTEN PTEN (Phosphatase and Tensin Homolog) mutation/expression)
  -  Prior treatment with at least one prior line of endocrine therapy and at least two and no more than three prior lines of chemotherapy for metastatic breast cancer
  -  Objective and radiologically confirmed progression of disease after prior treatment and at least one measurable lesion as per RECIST
  -  Adequate bone marrow and organ function
  Exclusion Criteria:
  -  Previous treatment with PI3K and/or mTOR inhibitors
  -  Symptomatic Central Nervous System (CNS) metastases
  -  Concurrent malignancy or malignancy in the last 5 years prior to start of study treatment
  -  Wide field radiotherapy ≤ 28 days or limited field radiation for palliation ≤ 14 days prior to starting study drug
  -  Active cardiac disease (e.g. Left Ventricular Ejection Fraction (LVEF) < 50%, QTcF > 480 msec on screening ECGelectrocardiogram (ECG), unstable angina pectoris, ventricular, supraventricular or nodal arrhythmias)
  -  Inadequately controlled hypertension
  -  Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BEZ235
  -  Treatment at start of study treatment with drugs with a known risk to induce Torsades de Pointes, moderate and strong inhibitors or inducers of isoenzyme CYP3A4, warfarin and coumadin analogues, LHRH agonists
  -  History of photosensitivity reactions to other drugs
  -  Pregnant or nursing (lactating) woman
  Other protocol-defined inclusion/exclusion criteria may apply

Relevance to patient case: not relevant
Patient case: 62-year-old male with cholangiocarcinoma; genetic feature: PIK3CA (1047H)

Clinical trial: Biomarkers in Tissue Samples From Older Women With Breast Cancer

Summary: This research trial studies phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutation analysis in tissue samples from older patients with stage I breast cancer. Studying samples of tissue from patients with stage I breast cancer in the laboratory may help doctors learn more about changes that occur in deoxyribonucleic acid (DNA) and identify biomarkers related to cancer.

Detailed description: PRIMARY OBJECTIVES:
  To assess the relapse free-survival difference between patients with PIK3CA mutated and wild-type (WT) tumors and therefore validate PIK3CA mutation status as an important biomarker in women 70 years or older diagnosed with breast cancer.
  OUTLINE:
  Previously collected tissue samples are analyzed via mutation analysis of PIK3CA.

Eligibility: -  Participants with stage I breast cancer (T1N0M0) and estrogen-receptor status positive or unknown
  -  Patients underwent lumpectomy with negative margins and were clinically node-negative

Relevance to patient case: not relevant
Patient case: 62-year-old male with cholangiocarcinoma; genetic feature: PIK3CA (1047H)

Clinical trial: A Study of BYL719 in Adult Patients With Advanced Solid Malignancies

Summary: In this study, BYL719 will be administered to adult patients with advanced solid tumors whose disease has progressed despite standard therapy or for whom no standard therapy exists. The trial will investigate the safety and tolerability and determine the MTD of BYL719 in Japanese patients.


Eligibility: Inclusion Criteria:
  -  Patients with histologically-confirmed, advanced unresectable solid tumors Availability of a representative formalin fixed paraffin embedded tumor tissue sample
  -  At least one measurable or non-measurable lesion Age ≥ 18 years
  -  Eastern Cooperative Oncology Group(ECOG) Performance Status ≤ 2 Good organ (hepatic, kidney, BM) function at screening/baseline visit
  Exclusion Criteria:
  -  Brain metastasis unless treated and free of signs/symptoms attributable to brain metastasis in the absence of corticosteroid therapy and anti-epileptic therapy.
  -  Prior treatment with PI3K inhibitor
  -  Patient with peripheral neuropathy NCI-CTC Grade ≥ 2
  -  Patient with diarrhea NCI-CTC Grade ≥ 2
  -  Patient with acute or chronic pancreatitis
  -  Impaired cardiac function or clinically significant cardiac disease incl unstable angina pectoris ≤ 3 months prior to starting study drug and Acute Myocardial Infarction (AMI) ≤ 3 months prior to starting study drug
  -  Patients with clinically manifest diabetes mellitus, history of gestational diabetes mellitus or documented steroid-induced diabetes mellitus
  -  Women who are pregnant or breast feeding or adults of reproductive potential not employing an effective method of birth control
  Other protocol-defined inclusion/exclusion criteria may apply

Relevance to patient case: not relevant
Patient case: 62-year-old male with cholangiocarcinoma; genetic feature: PIK3CA (1047H)

Clinical trial: A Phase I Study of Oral LGX818 in Adult Patients With Advanced or Metastatic BRAF Mutant Melanoma

Summary: CLGX818X2101 is a first-time in-human, phase I study to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of daily administered LGX818 (daily, twice daily and/or every-other-day), a RAF kinase inhibitor. Patients with locally advanced or metastatic melanoma harboring the BRAF V600 mutation (during dose escalation phase and expansion phase) and patients with metastatic colorectal cancer harboring the BRAF V600 mutation (during the expansion phase) will be enrolled. The study consists of a dose escalation part were cohorts of patients will receive escalating oral doses of LGX818, followed by a safety dose expansion part were patients will be treated with oral dose of LGX818 given at the MTD or RP2D.


Eligibility: Inclusion Criteria:
  For the dose escalation phase:
  1. Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage IIIB to IV per American Joint Committee on Cancer [AJCC]). For the dose expansion phase: (i) Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage IIIB to IV per American Joint Committee on Cancer [AJCC]), or (ii) confirmed diagnosis and non-resectable advanced metastatic colorectal cancer (mCRC) for which no further effective standard therapy exists.
  2. Written documentation of BRAF V600E mutation, or any other BRAF V600 mutation.
  3. Evidence of measurable disease
  Exclusion Criteria:
  1. Previous therapy with a MEK inhibitor.
  2. Symptomatic or untreated leptomeningeal disease.
  3. Symptomatic or untreated brain metastasis.Patients previously treated for these conditions that are asymptomatic in the absence of corticosteroid therapy are allowed to enroll. Brain metastasis must be stable with verification by imaging.
  4. Known acute or chronic pancreatitis.
  5. Clinically significant cardiac disease
  6. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LGX818
  7. Previous or concurrent malignancy. Exceptions to this exclusion criteria include: adequately treated basal cell or squamous cell skin cancer; in situ carcinoma of the cervix, treated curatively and without evidence of recurrence for at least 3 years prior to study entry; or other solid tumor treated curatively, and without evidence of recurrence for at least 3 years prior to study entry.
  8. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL).
  9. History of thromboembolic or cerebrovascular events within the last 6 months
  Other protocol-defined inclusion/exclusion criteria may apply

Relevance to patient case: not relevant
Patient case: 62-year-old male with cholangiocarcinoma; genetic feature: PIK3CA (1047H)

Clinical trial: Pilot Study of Irreversible Electroporation (IRE) to Treat Metastatic Liver Cancer & Cholangiocarcinoma

Summary: Single-arm pilot clinical trial. Patients will be subjected to irreversible electroporation (IRE) as the sole treatment of nodules not considered treatable by resection or thermal ablation.

Detailed description: Single-arm pilot clinical trial. Patients will be subjected to irreversible electroporation (IRE) as the sole treatment of nodules not considered treatable by resection or thermal ablation.
  This pilot study was designed to study the feasibility and safety of treatment as an alternative therapeutic IRE in the treatment of neoplastic nodules in the liver, with particular reference to metastatic liver cancer and cholangiocarcinoma, where the current therapeutic arsenal is inadequate or counter-indicated.
  To perform the IRE procedure the IRE NanoKnife™ System (AngioDynamics) will be used.

Eligibility: Inclusion Criteria:
  -  older than 18 years,
  -  male or female,
  -  diagnosis of secondary liver cancer or cholangiocarcinoma based on positive biopsy or noninvasive criteria,
  -  presence of at least one lesion untreatable by surgical resection or ablation for microwave or radio frequency,
  -  the target nodule must have a diameter of ≤ 5 cm
  -  ECOG score(Eastern Cooperative Oncology Group) 0,
  -  ASA score (American Society of Anesthesiologists) ≤ 3,
  -  prothrombin time ratio >50%
  -  platelet count >50x10^9/l,
  -  patient's ability to discontinue anticoagulant and antiplatelet therapy for seven days before and seven days after surgery with NanoKnife™,
  -  ability to understand and willingness to sign the written informed consent form (ICF),
  -  life expectancy of at least 3 months.
  Exclusion Criteria:
  -  presence of more than 5 liver lesions,
  -  previous treatment of the target nodule,
  -  patient received systemic chemotherapy within 30 days of treatment with the IRE NanoKnife™,
  -  heart failure, coronary artery disease or arrhythmia in progress, active implantable devices (eg pacemaker),
  -  pregnant women or women of childbearing potential not using an acceptable method of contraception,
  -  patient undergoing treatment with an investigational drug within 30 days of treatment with the IRE NanoKnife™,
  -  in the opinion of the researcher, anyone who can not follow the calendar of visits and assessments of the Protocol.

Relevance to patient case: not relevant
Patient case: 62-year-old male with cholangiocarcinoma; genetic feature: PIK3CA (1047H)

Clinical trial: Biomarkers in Patients With Head and Neck Cancer

Summary: RATIONALE: DNA analysis of tumor tissue may help doctors predict how well patients will respond to treatment.
  PURPOSE: This research study is studying biomarkers in patients with head and neck cancer.

Detailed description: OBJECTIVES:
  -  To determine the mutation rates of HRAS and PIK3CA in patients with head and neck squamous cell carcinoma (HNSCC) who were treated with cisplatin/placebo and cisplatin/cetuximab on protocol ECOG-E5397.
  -  To determine the association between HRAS or PIK3CA mutation status and clinical benefits (i.e., response, progression-free survival, and overall survival) in patients treated with cisplatin/cetuximab compared with those receiving cisplatin/placebo on protocol ECOG-E5397.
  OUTLINE: DNA is isolated from one unstained slide per patient. The mutations in HRAS and PIK3CA are determined using BEAMING technology.

Eligibility: DISEASE CHARACTERISTICS:
  -  Treated on protocol ECOG-E5397
  PATIENT CHARACTERISTICS:
  -  Not specified
  PRIOR CONCURRENT THERAPY:
  -  See Disease Characteristics

Relevance to patient case: not relevant
Patient case: 62-year-old male with cholangiocarcinoma; genetic feature: PIK3CA (1047H)

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: not relevant
Patient case: 62-year-old male with cholangiocarcinoma; genetic feature: PIK3CA (1047H)

Clinical trial: A Phase III Study of BKM120 With Fulvestrant in Patients With HR+,HER2-, AI Treated, Locally Advanced or Metastatic Breast Cancer Who Progressed on or After mTORi

Summary: This study was a multicenter, randomized, double-blind, placebo-controlled Phase III study to determine the efficacy and safety of treatment with Buparlisib plus Fulvestrant vs. Placebo plus Fulvestrant in postmenopausal women with hormone Receptor-positive (HR-positive), human epidermal growth factor receptor 2-negative (HER2-negative), aromatase inhibitor (AI)-treated, locally advanced or metastatic breast cancer whose disease progressed on or after mammalian target of rapamycin inhibitor (mTORi)-based treatment.
  Patients were randomized in 2:1 ratio to treatment with buparlisib 100 mg daily in combination with fulvestrant 500 mg or placebo daily in combination with fulvestrant 500 mg. Randomization was stratified according to visceral disease status (present or absent).

Detailed description: Novartis decided not to pursue further development of buparlisib program. On 19 Dec 2016, Novartis notified the Investigators about this decision; accordingly the CBKM120F2303 study was terminated.

Eligibility: Key inclusion criteria
  -  Female patients age 18 years or older
  -  Histologically and/or cytologically confirmed diagnosis of breast cancer
  -  Radiologic evidence of inoperable locally advanced or metastatic breast cancer
  -  Adequate tumor tissue for the analysis of PI3K-related biomarkers
  -  Human epidermal growth factor receptor-2 (HER2) negative disease, and a known positive hormone receptor status
  -  Postmenopausal women
  -  Prior treatment with aromatase inhibitors
  -  Evidence of progression to the combination of mTORi and endocrine therapy given as the last therapy prior to study entry
  -  Adequate bone marrow and organ function
  -  ECOG performance status ≤ 2
  Key exclusion criteria
  -  Previous treatment with PI3K inhibitors, protein kinase B inhibitors or fulvestrant
  -  More than one chemotherapy line for metastatic disease
  -  Hypersensitivity to any of the excipients of buparlisib or fulvestrant
  -  Symptomatic central nervous system metastases
  -  Concurrent malignancy or malignancy within 3 years of study enrollment
  -  Certain drugs or radiation within 2-4 weeks of enrollment
  -  Increasing or chronic treatment (>5 days) with corticosteroids or another immunosuppressive agent
  -  Certain scores on an anxiety and depression mood questionnaire given at screening
  -  Acute viral hepatitis or a history of chronic or active hepatitis B virus or hepatitis C virus
  -  Active cardiac disease or a history of cardiac dysfunction

Relevance to patient case: not relevant
Patient case: 62-year-old male with cholangiocarcinoma; genetic feature: PIK3CA (1047H)

Clinical trial: A Study of ZSTK474 in Japanese Patients With Advanced Solid Malignancies

Summary: To evaluate the safety (adverse events and dose-limiting toxicity) of daily oral doses of ZSTK474 in patients with advanced solid malignancies.

Detailed description: Open-label, uncontrolled, serial cohort, dose-escalation study evaluating two different dosing regimens (Arm 1: cycles of 5 days on drug and 2 days off drug), Arm 2: cycles of 21 days on drug and 7 days off drug).

Eligibility: Inclusion Criteria:
  -  Japanese males or females >= 20 years old
  -  Advanced (metastatic or unresectable) solid tumor
  -  ECOG performance status score of 0 or 1 and expected survival >12 weeks
  -  Recovered from hematological toxicities of prior cancer therapies
  Exclusion Criteria:
  -  Previous treatment with PI3K inhibitor
  -  Serious/significant illnesses or underlying conditions, including diabetes or hepatic renal or CV disease.
  -  Other investigational agent within previous 4 weeks
  -  Participating in another clinical study

Relevance to patient case: not relevant
Patient case: 62-year-old male with cholangiocarcinoma; genetic feature: PIK3CA (1047H)

Clinical trial: A Phase 1b Study Evaluating GS-9820 in Subjects With Lymphoid Malignancies

Summary: This study is to determine the appropriate dosing regimen of GS-9820 in subjects with lymphoid malignancies. This is a Phase 1b, open-label, dose-escalation and expansion study evaluating the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of GS-9820.


Eligibility: Inclusion Criteria:
  -  Previously treated recurrent B-cell iNHL, DLBCL, MCL, HL or CLL
  -  Measurable lymphadenopathy
  -  Requires therapy
  Exclusion Criteria:
  -  Recent history of a major non-lymphoid malignancy
  -  Evidence of ongoing infection
  -  Concurrent participation in another therapeutic clinical trial

Relevance to patient case: not relevant
Patient case: 62-year-old male with cholangiocarcinoma; genetic feature: PIK3CA (1047H)

Clinical trial: A Phase Ib/II Study of the Combination of BYL719 Plus AMG 479 in Adult Patients With Selected Solid Tumors

Summary: This was a multi-center, open-label, phase Ib/II study. The aim of the phase Ib part was to estimate the MTD(s) and/or identify the recommended phase II dose(s) (RP2Ds) for the combination of BYL719 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. Patients were to be treated until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. All patients were to be followed up. At a minimum, patients must have completed the safety follow-up assessments 30 days after the last dose of the study treatment.

Detailed description: This was a multi-center, open-label, phase Ib/II study. The aim of the phase Ib part was to estimate the MTD(s) and/or identify the recommended phase II dose(s) (RP2Ds) for the combination of BYL719 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 were to be guided by a Bayesian Logistic Regression Model (BLRM).
  Once MTD/RP2D had been determined, patients were to be enrolled in two Phase II arms. Patients with PIK3CA mutated or amplified hormone receptor positive breast carcinoma were to be enrolled in Arm 1; patients with PIK3CA mutated or amplified ovarian carcinoma were to be enrolled in Arm 2. Patients were to be treated until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. All patients were to be followed up. At a minimum, patients must have completed the safety follow-up assessments 30 days after the last dose of the study treatment.

Eligibility: Key inclusion criteria:
  -  Written informed consent.
  -  Patients aged ≥ 18 years (male or female).
  -  Patients with the following histologically/cytologically-confirmed advanced solid tumors with documented somatic PIK3CA mutations or amplifications in tumor tissue:
  -  Hormone receptor positive breast carcinoma
  -  Ovarian carcinoma
  -  Other tumors upon agreement with sponsor
  -  Adequate organ function
  -  Negative serum pregnancy test
  Key exclusion criteria:
  -  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 anti-coagulation therapy any time prior to enrollment.
  -  Clinically significant cardiac disease.
  -  History of another malignancy within last 2 years.
  -  Pregnant or nursing (lactating) women.

Relevance to patient case: possibly relevant