araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 70-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (V654A)

Clinical trial: Safety Study of IPI-504 in Patients With Gastrointestinal Stromal Tumors (GIST) or Soft Tissue Sarcomas (STS)

Summary: The primary objectives of the study are:
  -  Determine the safety and maximum tolerated dose (MTD) of IPI-504 in GIST and STS patients who have failed prior therapies
  -  Recommend a dose for subsequent studies of IPI-504

Detailed description: IPI-504 is a novel, water-soluble analog of 17-AAG and a potent inhibitor of Hsp90. Hsp90's role in the cell is to control the proper folding, function, and viability of various "client" proteins. Many of these client proteins (such as AKT, Her-2, Bcr-Abl, PDGFR-α, and c-Kit) are oncoproteins or important cell signaling proteins. In patients with GIST, mutations in the tyrosine kinase receptor Kit play a critical role in the pathogenesis of this disease. Inhibition of Kit signaling with the tyrosine kinase inhibitor Imatinib (IM) is a very effective treatment for GIST patients. However, new mutations arise in Kit conferring resistance to IM treatment which results in disease progression. Kit is a client protein of Hsp90 and is sensitive to IPI-504. In Soft Tissue Sarcomas, there may be genetic abnormalities that lead to the expression of certain proteins that drive the growth of cancer. These cancer-driving proteins may be stimulated by HSP90. This provides a scientific rationale for Phase 1 clinical testing of IPI-504 in patients with advanced GIST and STS who have failed prior therapies.

Eligibility: Inclusion Criteria:
  -  Pathologically confirmed diagnosis of GIST or STS
  -  Failed prior therapies
  -  ECOG performance status of 0-2
  -  Ability to adhere to the study visit schedule and all protocol requirements
  Exclusion Criteria:
  -  Previous treatment with 17-AAG, DMAG, or other known Hsp90 inhibitor
  -  Participation in any investigational drug study or treatment with any other kinase inhibitor therapy within 2 weeks preceding start of treatment
  -  Concurrent radiation therapy is not permitted
  -  Concurrent treatment with any agent that alters CYP3A activity
  -  Concurrent treatment with any agent that may prolong the QTc interval
  -  Myocardial infarction or active ischemic heart disease within 6 months
  -  History of arrhythmia
  -  Baseline QTc >450
  -  Grade 3 or greater peripheral neuropathy
  -  Renal insufficiency, serum creatinine >1.5 x ULN
  -  Platelets < 100,000 mm3
  -  AST and / or ALT > 2.5 x ULN
  -  ANC <1,500 cells/mm3
  -  Alkaline phosphatase > 2.5 x ULN
  -  Amylase and lipase > 1.5 x ULN
  -  Hemoglobin < 9.0 g/dL

Relevance to patient case: possibly relevant
Patient case: 70-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (V654A)

Clinical trial: Study of XL647 Administered Orally Daily to Patients With Solid Tumors

Summary: The purpose of this study is to assess the safety and tolerability of the multiple receptor tyrosine kinase (RTK) inhibitor (including EGFR, VEGFR2, ErbB2, and EphB4) XL647 when given orally daily to adults with advanced solid tumors.


Eligibility: Inclusion Criteria:
  -  Subject has histologically confirmed malignancy that is metastatic or unresectable
  -  Subject has disease that is assessable by tumor marker, physical, or radiologic means
  -  Subject is at least 18 years old
  -  Subject has an ECOG performance status ≤ 2 (Karnofsky ≥ 60%)
  -  Subject has a life expectancy ≥ 3 months
  -  Subject has normal organ and marrow function
  -  Subject gives written informed consent
  -  Subject must use an accepted method of contraception during the study
  -  Female subjects of childbearing potential must have a negative pregnancy test
  Exclusion Criteria:
  -  Subject has received anticancer treatment within 30 days of first dose of XL647
  -  Subject has received another investigational agent within 30 days of first dose of XL647
  -  Subject has known brain metastases
  -  Subject has corrected QT interval (QTc) of > 0.45 seconds
  -  Subject is currently receiving anticoagulation therapy with warfarin
  -  Subject has uncontrolled intercurrent illness
  -  Subject is pregnant or breastfeeding
  -  Subject has known HIV

Relevance to patient case: not relevant
Patient case: 70-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (V654A)

Clinical trial: Study of XL647 in Subjects With Non-Small-Cell Lung Cancer

Summary: The purpose of this phase II study is to determine the safety, tolerability, and activity of XL647 in previously untreated subjects with non-small cell lung cancer (NSCLC). XL647 is a small molecule that potently inhibits multiple receptor kinases, including EGFR, VEGFR2 (KDR), ErbB2, and EphB4. Sensitivity to EGFR inhibitors has been linked to specific EGFR mutations and associated with certain clinical characteristics in patients with NSCLC (eg, female, minimal and remote smoking history, and adenocarcinoma histology).


Eligibility: Inclusion Criteria:
  -  Subject has NSCLC with a histologically confirmed diagnosis of adenocarcinoma with measurable disease (stage IIIB, with malignant pleural effusion, and stage IV) and either has a demonstrated activating mutation of the EGF receptor in tumor tissue or meets one of three criteria: asian, female, and minimal or no smoking history.
  -  Measurable disease defined according to RECIST
  -  ECOG performance status of 0 or 1
  -  Normal organ and marrow function
  -  No other malignancies within 5 years, except for non-melanoma skin cancer
  Exclusion Criteria:
  -  Radiation to ≥25% of bone marrow within 30 days of XL647 treatment
  -  Prior systemic anticancer therapy, including cytotoxic chemotherapy, anti-VEGF, anti-VEGFR, or anti-EGFR agents or investigational drug
  -  Subject has not recovered to ≤ grade 1 or to within 10% of baseline values from adverse events due to other medications administered > 30 days before study enrollment
  -  Receiving anticoagulation therapy with warfarin (low-dose warfarin < 1 mg/day, heparin and low molecular weight heparins are permitted)
  -  The subject meets any of the following cardiac criteria:
  -  Corrected QT interval (QTc) of > 460 msec
  -  Family history of congenital long QT syndrome or unexplained sudden death
  -  History of sustained ventricular arrhythmias
  -  Has a finding of left bundle branch block
  -  Has an obligate pacemaker
  -  Has important bradycardia defined as a heart rate of < 50 bpm due to sinus node dysfunction
  -  Has uncontrolled hypertension
  -  Has symptomatic congestive heart failure, unstable angina, or a myocardial infarction within the past 3 months
  -  Has a serum potassium or serum magnesium level that falls outside the normal range
  -  The subject has progressive symptomatic or hemorrhagic brain or leptomeningeal metastases
  -  Uncontrolled intercurrent illness
  -  Subject is pregnant or breastfeeding
  -  Known HIV

Relevance to patient case: not relevant
Patient case: 70-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (V654A)

Clinical trial: Safety And Effectiveness Of Daily Dosing With Sunitinib Or Imatinib In Patients With Gastrointestinal Stromal Tumors

Summary: A phase IIIb study of patients with gastrointestinal stromal tumors who have had progressive disease while on 400 mg imatinib. Patients will be randomly assigned to either sunitinib 37.5 mg daily or imatinib 800 mg daily. This study will find out the benefits and potential side effects of taking sunitinib or imatinib for approximately one year.

Detailed description: The study prematurely discontinued on July 27, 2009 due to poor recruitment and operational futility as a result of changes in clinical practice. There were no safety or efficacy concerns regarding the study in the decision to terminate the trial.

Eligibility: Inclusion Criteria:
  -  Patients with gastrointestinal stromal tumors whose disease has progressed on imatinib 400 mg daily.
  Exclusion Criteria:
  -  Current treatment with any chemotherapy other than imatinib.
  -  Current treatment with any dose of imatinib other than 400 mg

Relevance to patient case: not relevant
Patient case: 70-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (V654A)

Clinical trial: Study Tests The Safety And Effectiveness Of SU011248 In Patients With Non-Small Cell Lung Cancer Having Brain Metastases

Summary: This study will evaluate the safety, tolerability and efficacy of SU011248 in patients with non-small cell lung cancer with brain metastases.


Eligibility: Inclusion Criteria:
  -  Patients with radiologically proven brain metastases secondary to non-small cell lung cancer
  -  Received previous whole brain radiation therapy and none, 1 or 2 prior systemic therapy for the treatment of advanced/metastatic non-small cell lung cancer
  Exclusion Criteria:
  -  Patients with brainstem lesions, spinal cord compression. carcinomatous meningitis, or leptomeningeal disease.
  -  Brain metastases >4 cm in any linear direction
  -  Intracranial or intratumoral hemorrhage

Relevance to patient case: not relevant
Patient case: 70-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (V654A)

Clinical trial: The Biological Activity of Cediranib (AZD2171) in Gastro-Intestinal Stromal Tumours(GIST).

Summary: To determine the anti-tumour activity and biological effects of cediranib (AZD2171) at a dose of 45mg, primarily in Gastrointestinal Stromal Tumour (GIST) patients who are resistant to imatinib mesylate (current standard therapy) and also in patients with metastatic Soft Tissue Sarcoma (STS) resistant to standard therapy.


Eligibility: Inclusion Criteria:
  -  Histological or cytological confirmation of GIST which is resistant or intolerant to imatinib mesylate, or metastatic STS, which is refractory to standard therapies or for which no standard therapy exists
  Exclusion Criteria:
  -  Patients with type I insulin-dependent diabetes or poorly-controlled type II insulin-independent diabetes.
  -  Patients with a history of poorly controlled high blood pressure

Relevance to patient case: not relevant
Patient case: 70-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (V654A)

Clinical trial: Evaluation of Diagnostic Value of Molecular Markers in Renal Cancer

Summary: Renal cancer is frequent and its diagnosis mainly dependant on imaging. More than 50% of renal tumors are currently diagnosed without symptoms. However, 20% of small solid tumors are benign and this percentage is much higher in atypical cystic tumors Bosniak II and III, where 76% and 59% are benign respectively. Determining the malignancy by imaging in these cases is difficult and sometimes impossible. The fine needle aspiration (FNA) cytology or biopsy is necessary. The diagnostic sensitivity and specificity with biopsy are high, but the potential tumor contamination is a major risk. The FNA cytology is simple and safe, but its sensitivity is about 50%. We are conducting a multicentric prospective study to add the molecular markers in FNA cytology as a new diagnostic method in imaging-indeterminate renal tumors.
  Four molecular markers including MN/CA9, vimentin, KIT, and S100A1 will be studied. These four markers have been reported to have a differential diagnostic value in renal tumors. MN/CA9 and vimentin are often found in conventional renal cancers. KIT is frequently expressed in renal oncocytomas and chromophobe renal cancers. S100A1 may further distinguish renal oncocytoma from chromophobe renal cancer. These markers will be analyzed by real time polymerase chain reaction (RT-PCR).
  The aim of this study is to evaluate the diagnostic performance of the association cytology-molecular markers in imaging-indeterminate renal tumors (small solid tumors and cystic tumors ≥ Bosniak III). About 156 patients will be included in five French clinical centers including Saint-Etienne, Marseille, Grenoble, Toulouse, and Nancy.
  The expected results will improve the preoperative diagnostic accuracy in renal tumors.


Eligibility: Inclusion Criteria:
  -  Clinical diagnosis of kidney tumor < 4 cm
  -  Cystic kidney tumor (Bosniak > IIF)
  -  Consent signed
  Exclusion Criteria:
  -  Benign tumor confirmed
  -  Impossibility to do abdominal pelvic ultra-sound or abdominal thoracic scanner
  -  Contraindication for renal puncture

Relevance to patient case: not relevant
Patient case: 70-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (V654A)

Clinical trial: A Phase 2 Study of XL820 in Adults With Advanced GIST Resistant to Imatinib and/or Sunitinib

Summary: The purpose of this study is to evaluate the clinical benefit of the KIT inhibitor XL820 in subjects with advanced gastrointestinal stromal tumors (GIST) who are resistant to or intolerant of Imatinib and/or Sunitinib.


Eligibility: Inclusion Criteria:
  -  Patients with metastatic or locally advanced or unresectable GIST who have intolerance of or disease progression following prior treatment with imatinib and/or sunitinib
  -  ECOG (Eastern Cooperative Oncology Group) performance status ≤2
  -  Must have measurable disease per RECIST (Response Evaluation Criteria in Solid Tumors)
  -  Recovery from toxicity from prior therapy to Common Terminology Criteria for Adverse Events (CTCAE) v3.0 Grade ≤1 or to subject's baseline status
  -  Adequate organ and marrow function
  -  Sexually active subjects (male and female) must agree to use accepted methods of contraception during the course of the study and for 3 months following discontinuation of study drugs.
  -  Female subjects of childbearing potential must have a negative pregnancy test at enrollment.
  Exclusion Criteria:
  -  Therapy with imatinib or sunitinib within 14 days before the first dose of study drug
  -  Chemotherapy, immunotherapy, targeted therapy, chemoembolization, or any investigational drug for the treatment of GIST after the last dose of imatinib or sunitinib
  -  Anticoagulation with warfarin or coumarin-related compounds
  -  Radiation to ≥25% of bone marrow within 28 days of study entry
  -  Treatment with other investigational agents within 28 days of the first dose of XL820
  -  Known central nervous systems metastases
  -  Uncontrolled or intercurrent illness
  -  Pregnancy or breast-feeding
  -  Active bacterial or viral infection requiring systemic treatment

Relevance to patient case: definitely relevant
Patient case: 70-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (V654A)

Clinical trial: A Study Of Oral PF-02341066, A C-Met/Hepatocyte Growth Factor Tyrosine Kinase Inhibitor, In Patients With Advanced Cancer

Summary: PF-02341066 may work in cancer by blocking the cell growth, migration and invasion of tumor cells. PF-02341066 is a new class of drugs called c-Met/Hepatocyte growth factor receptor tyrosine kinase inhibitors. This compound is also an inhibitor of the anaplastic lymphoma kinase (called ALK) tyrosine kinase and ROS receptor tyrosine kinases. This research study is the first time PF-02341066 will be given to people. PF-02341066 is taken by mouth daily.


Eligibility: Inclusion Criteria:
  -  Advanced malignancies (except leukemias), histologically proven at diagnosis; Histologically confirmed advanced malignancies that are known to be sensitive to PF-03241066 inhibition, e.g. ALK, c-MET and ROS
  -  Solid tumors must have measurable disease (Recommended Phase 2 Dose Cohort patients with non-measurable disease may enter on a case-by-case basis); not required for DDI sub-studies.
  -  Adequate blood cell counts, kidney function, liver function and Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 (for the Recommended Phase 2 Cohort, a ECOG score of 2 may be allowed on a case-by-case basis)
  Exclusion Criteria:
  -  Major surgery, radiation therapy or anti-cancer therapy within 2 to 4 weeks of starting study treatment, depending on the patient cohort
  -  Prior stem cell transplant except of patients with neuroblastoma, lymphoma or myeloma
  -  Active or unstable cardiac disease or heart attack within 3 months of starting study treatment

Relevance to patient case: not relevant
Patient case: 70-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (V654A)

Clinical trial: Efficacy Analysis of Cetuximab Plus Irinotecan in Patients With Wild-type KRAS Without Regard to Epidermal Growth Factor Receptor (EGFR) Expressions

Summary: The purpose of this study is to investigate the response rate of cetuximab plus irinotecan every 2 weeks in patients harboring wild-type KRAS with and without detectable EGFR-expressing metastatic CRC after failure to irinotecan in an exploratory manner.

Detailed description: Twenty patients with positive-EGFR results and 20 patients with negative-EGFR results will be accrued in this study. All patients should have wild-type KRAS.

Eligibility: Inclusion Criteria:
  -  Colorectal adenocarcinoma, Wild KRAS, 18-75 yr
  -  Estimated life expectancy of more than 3 months
  -  ECOG performance status of 0 to 1 at study entry
  -  Adequate bone marrow function
  -  Adequate liver function
  -  Documented progression during or within 3 months of irinotecan-containing regimens as a first-line chemotherapy
  -  Immunohistochemical evidence of a presence or absence of EGFR expression by PharmDx Kit
  -  Informed Consent
  Exclusion Criteria:
  -  Central nervous system (CNS) metastases or prior radiation for CNS metastases.
  -  Intestinal obstruction or impending intestinal obstruction due to peritoneal carcinomatosis
  -  Surgery (excluding biopsy for diagnosis) during 4 weeks prior to inclusion in the study.
  -  Evidence of gastrointestinal bleeding
  -  Exposure to Cetuximab
  -  Prior administration of monoclonal antibodies, EGFR signal transduction inhibitors or EGFR-targeted treatment
  -  KRAS mutant Status
  -  Patients with serious toxicity to previous irinotecan-based chemotherapy
  -  Other serious illness or medical conditions

Relevance to patient case: not relevant
Patient case: 70-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (V654A)

Clinical trial: Kinase Genotyping of Gastro Intestinal Stomach Tumors (GISTs) From Patients Enrolled in Pfizer A6181112 Phase IIIb Trial

Summary: The purpose of this study is to determine the genetic makeup of gastro intestinal stomach tumors (GISTs) from patients enrolled in the A6181112 phase IIIb trial. Tumor samples will be screened for mutations and this information will be used to determine whether the progression-free survival of patients being treated with the cancer medication sunitinib is related to the underlying genotype of their GIST.

Detailed description: In this companion study, we will analyze the genomic DNA from the GIST tumor specimens of patients enrolled in the in the A6181112 phase IIIb trial at participating U.S. and ex-U.S. medical centers. Specifically, GIST samples will be screened for mutations in KIT gene exons 9, 11, 13 and 17, and PDGFRA gene exons 12, 14 and 18, to determine the primary kinase genotype. Subset analyses will be performed and compared with the overall PFS rates observed in patients with primary and secondary imatinib resistance. Based on data from a previous phase I/II trial, our hypothesis is that patients with either primary or secondary imatinib resistance having a KIT exon 9-mutant or WT GIST will have a longer PFS when treated with sunitinib than patients with exon 11-mutant GIST. We further hypothesize that this difference will be observed among patients treated with high-dose imatinib.

Eligibility: Inclusion Criteria:
  -  Patients enrolled in Pfizer A6181112
  Exclusion Criteria:
  -  Patients who do not consent for analysis of their tumor in this companion study

Relevance to patient case: not relevant
Patient case: 70-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (V654A)

Clinical trial: Characterisation of Gene Variants in the Angiogenic Pathway

Summary: Anti-angiogenic targeted therapies are used in a wide range of solid tumors including NSCLC, breast cancer, GISTs, CRC, renal cell carcinoma and hepatocellular carcinoma. Somatic mutations in genes related to tumorigenesis have been associated with treatment response whereas germline gene variants have been associated with tumor risk, prognosis and treatment related toxicity.Study objectives are:
  1. To characterise the prevalence and clinicopathological associations of germline and somatic variation in genes involved in the angiogenic pathway in healthy donors and unselected cancer patients
  2. To examine the association between angiogenic gene variants and outcome in patients receiving anti-angiogenic therapy

Detailed description: Angiogenesis plays a key role in the process of tumour growth and metastases. Anti-angiogenic targeted therapies are currently used in a wide range of solid tumors including lung, breast, colorectal, kidney and liver cancer. Somatic variants in genes related to tumorigenesis have been associated with treatment response, whereas germline gene variants have been associated with tumor risk, prognosis and treatment related toxicity. In this study we propose to (1) To characterise the prevalence and clinicopathological associations of germline and somatic variation in genes involved in the angiogenic pathway in healthy donors and unselected cancer patients (2) to examine the association between angiogenic gene variants and outcome in patients receiving anti-angiogenic therapy. Genes related to angiogenesis to be characterised include those encoding platelet derived growth factor receptors, vascular endothelial growth factors, vascular endothelial growth factor receptors, K-Ras, B-Raf, and c-kit. Results from this study may (1) identify patients who are more likely to respond to anti-angiogenic targeted therapy, thus maximising drug efficacy and (2) to identify further targets for potential anti-angiogenic drug therapies.

Eligibility: Inclusion Criteria:
  -  Anti-angiogenic targeted therapies are used in a wide range of solid tumors including NSCLC, breast cancer, GISTs, CRC, renal cell carcinoma and hepatocellular carcinoma

Relevance to patient case: not relevant
Patient case: 70-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (V654A)

Clinical trial: Special Investigation For Gist Of Sunitinib Malate (Regulatory Post Marketing Commitment Plan).

Summary: The objective of this surveillance is to collect information about 1) adverse drug reaction not expected from the LPD (unknown adverse drug reaction), 2) the incidence of adverse drug reactions in this surveillance, and 3)factors considered to affect the safety and/or efficacy of this drug.

Detailed description: All the patients whom an investigator prescribes the first SUNITINIB MALATE(Sutent) should be registered.

Eligibility: Inclusion Criteria:
  Patients need to be administered SUNITINIB MALATE(Sutent) in order to be enrolled in the surveillance.
  Exclusion Criteria:
  Patients not administered SUNITINIB MALATE(Sutent).

Relevance to patient case: definitely relevant