araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

Clinical trial: Evaluate the Efficacy of AMG 706 to Treat Advanced Gastrointestinal Stromal Tumors

Summary: The purpose of the study is to evaluate the safety and efficacy of AMG 706 in patients with gastrointestinal stromal tumor that have not been controlled while taking imatinib mesylate.


Eligibility: Inclusion Criteria:
  -  Diagnosis of histological confirmed GIST
  -  Had prior imatinib mesylate therapy
  -  Has at least 1 measurable leasion by modified RECIST
  Exclusion Criteria:
  -  Central nervous system tumor involvement requiring treatment
  -  History of myocardial infraction
  -  Uncontrolled hypertension

Relevance to patient case: not relevant
Patient case: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

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: not relevant
Patient case: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

Clinical trial: Chromosome Abnormalities in Chronic Myeloid Leukemia (CML) on Imatinib. GIST Patients on Imatinib

Summary: In order to distinguish between clonal instability driven by imatinib in CML and actual changes with secondary clones induced by imatinib we would like to investigate the karyotype of non-CML patients treated with imatinib such as GIST patients.

Detailed description: Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the presence of the Philadelphia (Ph) chromosome - a t(9:22) translocation that results in the production of a BCR/ABL fusion protein with Abl kinase activity.
  Imatinib mesylate (Gleevec) specifically targets a limited set of protein tyrosine kinases - ABL, Arg (Abl-related gene), c-Kit, platelet-derived growth factor receptor (PDGF-R) - and their oncogenic forms, most notably BCR/ABL Imatinib is also a potent inhibitor of a receptor-type c-Kit tyrosine kinase. Therefore imatinib was examined for therapeutic efficacy against malignant gastro-intestinal stromal tumors (GIST) Recent articles have drawn attention to the development of new Ph-negative, cytogenetically unrelated clones after therapy of Ph-positive CML with imatinib. Trisomy 8 and monosomy 7 are the most frequent defects, but other aberrations have also been reported. Some of these cytogenetic abnormalities are associated with acute myeloid leukemia and MDS.

Eligibility: Inclusion Criteria:
  -  GIST patient on Imatinib for more than 12 months
  Exclusion Criteria:
  -  nil

Relevance to patient case: not relevant
Patient case: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

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: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

Clinical trial: Study of XL647 in Subjects With NSCLC Who Have Progressed After Responding to Treatment With Gefitinib or Erlotinib

Summary: The purpose of this study is to determine the best confirmed response rate of daily administration of the multiple receptor tyrosine kinase (RTK) inhibitor (including EGFR and VEGFR2) XL647 in subjects with NSCLC who have progressed after responding to treatment with either erlotinib or gefitinib.


Eligibility: Inclusion Criteria:
  -  Histologically confirmed diagnosis of unresectable Stage IIIB or Stage IV relapsed or recurrent NSCLC.
  -  Subjects must have:
  1. documented (radiological or clinical) progressive disease (PD) following a prior response (including stable disease) to monotherapy with erlotinib or gefitinib that was administered for at least 12 weeks prior to progression OR
  2. a documented T790M EGFR mutation
  -  Measurable disease defined according to RECIST
  -  ECOG performance status of 0 or 1.
  -  Sexually active subjects must use an accepted method of contraception during the course of the study.
  -  Female subjects of childbearing potential must have a negative pregnancy test at enrollment.
  Exclusion Criteria:
  -  Received radiation to ≥25% of his or her bone marrow within 30 days of XL647 treatment.
  -  Received erlotinib or gefitinib, or other anticancer therapy within 14 days of the first dose of study drug.
  -  Received an investigational drug (excluding erlotinib or gefitinib) within 30 days of the first dose of study drug.
  -  Receiving anticoagulation therapy with warfarin.
  -  Not recovered to Grade ≤1 from adverse events (AEs) due to antineoplastic agents, investigational drugs, or other medications that were administered prior to study enrollment.
  -  Corrected QT interval (QTc) of >0.45 seconds.
  -  Progressive, symptomatic, or hemorrhagic brain or leptomeningeal metastases.
  -  Requires steroid or anticonvulsant therapy for the treatment of brain metastases.

Relevance to patient case: not relevant
Patient case: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

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: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

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: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

Clinical trial: Open Label Safety & Pharmacodynamic Study 24Wk w/DIO-902 Combo w/Metformin & Atorvastatin in T2DM Patients

Summary: DiObex Inc. is developing an experimental drug (DIO-902) that is made up of part of the ketoconazole molecule for the treatment of elevated blood glucose associated with type 2 diabetes mellitus. Ketoconazole (Nizoral®) is a drug available by prescription for the treatment of fungal infections however DIO-902 is an investigational drug. DIO-902 may lower blood glucose by lowering levels of a naturally occurring hormone called cortisol. Elevated cortisol may contribute to the development of type 2 diabetes.

Detailed description: To maintain the blind in Protocol DIO-502, subjects will be re-randomized at Study Visit 1 to one of three doses of DIO-902: 150, 300 or 450 mg QHS. All subjects receiving DIO-902 placebo and 50% of subjects receiving DIO-902 will be re-randomized to one of three DIO-902 doses. The remaining 50% of subjects receiving DIO-902 will be assigned to their original DIO-902 dose. The re- randomization will be performed by a group independent of study conduct to ensure the treatment status of the subject while in Protocol DIO-502 remains blinded. In addition, subjects will continue on the same dose of metformin that they had been taking during the conduct of Protocol DIO-502. Subjects will continue on atorvastatin 10 mg for the first 4 weeks of this protocol. Thereafter, at Study Visits 3 and 4, the dose of atorvastatin may be increased up to a maximum of 40 mg daily in order to achieve LDL-cholesterol/non-HDL cholesterol goals specified within the protocol. In addition, after Study Visit 4 (Week 12) subjects with HbA1c levels of > 7.5% (0.075 Hb Fract.) will undergo a one time titration of their oral hypoglycemic regimen as per the algorithm provided in the protocol.

Eligibility: Inclusion Criteria:
  -  Participated in DIO-502
  Exclusion Criteria:
  -  Did not participate in DIO-502

Relevance to patient case: not relevant
Patient case: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

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: definitely relevant
Patient case: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

Clinical trial: A Phase IIa Proof-of-concept Study of NC-503 in Patients With Type II Diabetes

Summary: The main objectives of the current study are to establish the safety and clinical proof-of-concept of NC-503 in inadequately controlled patients with Type 2 diabetes and features of metabolic syndrome treated with either metformin, a sulfonylurea agent, or metformin in combination with a sulfonylurea agent.

Detailed description: Phase IIa Multi-center, randomized, double-blind, placebo-controlled and parallel-designed study.

Eligibility: Inclusion Criteria:
  -  Age and gender eligibility: 30 years and older
  -  Diagnosis of Type 2 diabetes mellitus
  -  Patients treated with a stable therapeutic dose of either metformin, a sulfonylurea agent, or metformin in combination with a sulfonylurea agent for a minimum period of 3 months prior to the Screening visit
  -  Patients must have HbA1C level between 7.0-10.0 %, inclusively at screening
  -  The participant must have central obesity (Waist circumference) defined per country/ethnic group: Europids: men ≥ 94 cm, women ≥ 80 cm; South Asian, Chinese & Japanese: men ≥ 90 cm, women ≥ 80 cm; and any one of the following metabolic syndrome characteristics at screening:
  -  Reduced HDL cholesterol ≤ 1.0 mmol/L
  -  Hypertriglyceridemia ≥ 1.7 mmol/L or treatment for dyslipidemia
  -  Hypertension: ≥ 130/85 mm Hg blood pressure or treatment with antihypertensive medication.
  -  Patients must have a Glomerular Filtration Rate (GFR) of ≥ 60 mL/min, and no history of dialysis.
  Exclusion Criteria:
  -  Patients having received insulin, thiazolidinediones (TZDs) or non-thiazolidinedione hypoglycemic agents other than metformin or sulfonylurea agents within three months prior to screening
  -  Has had, within the last 6 months, evidence of significant heart disease or stroke, including myocardial infarction, unstable angina, coronary bypass and/or percutaneous transluminal coronary angioplasty (PTCA), congestive heart failure (New York Heart Association Class III-IV), or severe ischemic disease
  -  Patients who have an increased red blood cell (RBC) turn-over or Thalassemia or anemia
  -  Known HIV or history of viral hepatitis type B or C.
  -  Any type of diabetes other than Type 2 diabetes
  -  Significant hepatic enzyme elevation
  -  Body mass index (BMI) of > 40kg/m2
  -  Current or previous use of oral or injectable corticosteroids, or conditions that require the use of corticosteroids, during the three months prior to screening

Relevance to patient case: not relevant
Patient case: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

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: not relevant
Patient case: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

Clinical trial: A Retrospective Clinical Records Review of Patients Diagnosed With Gastrointestinal Stromal Tumour at Two Tertiary Institutes in Singapore

Summary: To review the characteristics and treatment of gastrointestinal tumours at the two tertiary centres in Singapore

Detailed description: A retrospective clinical records review of patients diagnosed with gastrointestinal stromal tumour (GIST) in the two tertiary centres in Singapore i.e. Singapore General Hospital and National University Hospital.
  Gastrointestinal tumours are the most common soft-tissue tumours of the gastrointestinal tracts. Remarkable progress has been made during the last several years in the diagnosis and treatment of GIST. Understanding of the molecular pathogenesis of GIST which is linked to deregulated KIT tyrosine-kinase activity has improved diagnosis, such that GIST is now more frequently and specifically identified. More importantly, systemic tyrosine kinase inhibitor, imatinib, has been used successfully in the treatment of GIST patients with advanced or unresectable disease.
  GIST has been reviewed in the Western literature but there is a lack of Asian data. The review will help us to better understand the disease in our population.Furthermore we will also examine several unresolved issues in the Western literature by looking into our local data. These include required duration of imatinib therapy, role of imatinib in the adjuvant setting (application of chemotherapy after macroscopically complete removal of tumour) and role of combination therapies.
  The medical records of all patients diagnosed with the disease at the two centres will be reviewed.
  Analysis of the results aims to:
  1. to compare the characteristics of the GIST (epidemiology, site, morphology, immunohistochemistry profile) in our centres compared to the well-published literature.
  2. to compare the treatment regimen and results of our centres compared to others
  3. to review the role of chemotherapy in the adjuvant settings in the centres.

Eligibility: Inclusion Criteria:
  -  Patients diagnosed with Gastrointestinal stromal tumor.

Relevance to patient case: not relevant