araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 49-year-old female with Gastrointestinal stromal tumor. Genetic variant: KIT Exon 9 (A502_Y503dup). Other conditions: None.

Clinical trial: Development of a Diagnostic Kit for FLT3-ITD in Acute Myeloid Leukemia

Summary: FLT3 overexpression in acute myeloid leukemia (AML) is often caused by mutations in this gene. These mutations cause constitutive phosphorylation of FLT3 proteins leading to increased proliferation and survival, decreased apoptosis and resistance to chemotherapeutic agents in AML cells. There are two major types of FLT3 mutations- internal tandem duplication (ITD) and point mutation at 835th amino residue. AMLs with FLT3 mutations have worse prognosis and are often resistant to conventional chemotherapy. Several small molecule compounds targeting FLT3 have been in the market or in clinical trials. Therefore, identification of these mutations at the time of diagnosis will provide a better prognostic prediction, might guide the treatment selection and follow-up strategies. In this study, the investigators will develop a sensitive molecular assay to detect FLT3 mutations for future clinical application. The investigators will collect 100 AML samples with at least 20 samples with known FLT3 mutations. The investigators will compare this assay with commonly used methods and standardize the procedure to meet the requirement of clinical pathology laboratory with reasonable cost.


Eligibility: Inclusion Criteria:
  -  Patients with confirmed diagnosis of acute myeloid leukemia
  Exclusion Criteria:
  -  non

Relevance to patient case: not relevant
Patient case: 49-year-old female with Gastrointestinal stromal tumor. Genetic variant: KIT Exon 9 (A502_Y503dup). Other conditions: None.

Clinical trial: Rechallenge of Imatinib in GIST Having no Effective Treatment

Summary: The objective of this study is to compare the clinical outcomes following resumption of dosing (re-challenge) with Imatinib plus best supportive care versus placebo plus best supportive care in patients with advanced/incurable Gastrointestinal Stromal Tumors following failure of prior imatinib and sunitinib therapies.


Eligibility: Inclusion Criteria:
  -  Patients aged 18 years and older
  -  Patients with metastatic or unresectable malignant gastrointestinal stromal tumour which has been histologically confirmed by the detection of CD117 on immunohistochemical staining or genetically confirmed by the detection of mutation in KIT or PDGFRα genes on direct sequencing of tumor DNA.
  -  Prior benefit from 1st line imatinib defined as complete response, partial response, or stable disease at 6 months after the start of 1st line imatinib
  -  Patients whose disease has progressed despite at least both prior imatinib therapy (400mg/day) and then subsequently also failure of prior sunitinib therapy.
  -  ECOG(Eastern Cooperative Oncology Group) performance status 0 ~ 3
  -  Adequate bone marrow function as defined by platelets ≥ 75 x 109/L and neutrophils ≥ 1.5 x 109/L
  -  Adequate renal function, with serum creatinine < 1.5 x upper limit of normal
  -  Adequate hepatic function with serum total bilirubin < 1.5 x upper limit of normal, alanine aminotransferase or aspartate aminotransferase < 2.5 x upper limit of normal in the absence of liver metastases, or < 5 x upper limit of normal in the presence of liver metastases.
  -  Expected life expectancy of greater than 12 weeks in the absence of any intervention
  -  No other malignant disease apart from non-melanotic skin cancer or carcinoma in situ of the uterine cervix or any other cancer except where treated with curative intent > 5 years previously without evidence of relapse
  -  Written, informed consent to the study
  Exclusion Criteria:
  -  Medical or psychiatric conditions that compromise the patient's ability to give informed consent or to complete the protocol or a history of non- compliance
  -  Last dose of radiotherapy received within 4 weeks before the start of study treatment, excluding palliative radiotherapy
  -  Obstruction of gastrointestinal tract
  -  Active gastrointestinal bleeding
  -  Myocardial infarction within 6 months prior to the study medication, and other clinically significant heart disease (e.g., unstable angina, congestive heart failure or uncontrolled hypertension)
  -  Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the study or which would jeopardise compliance with the protocol
  -  Female patients who are pregnant or breast-feeding. Female patients must have had a negative pregnancy test within one week before starting imatinib.

Relevance to patient case: possibly relevant
Patient case: 49-year-old female with Gastrointestinal stromal tumor. Genetic variant: KIT Exon 9 (A502_Y503dup). Other conditions: None.

Clinical trial: A Retrospective Study of C-kit Mutation Status in Asian Patients With Advanced Gastro-intestinal Stromal Tumors (GIST) Treated With Imatinib.

Summary: Imatinib is the current standard treatment for advanced GIST. Previous studies have shown that GIST genotype was associated with treatment outcomes with exon 11 having superior outcome compared with exon 9 or WT.10, 11 In patients with exon 9 kit mutation, the response rate was higher at when imatinib was given at 800mg daily compared with the standard dose of 400mg daily. Although the data linking tyrosine kinase mutation status and imatinib response in metastatic GISTs is intriguing, more information is needed before mutation testing is adopted as part of the routine analysis of high-risk or overtly malignant KIT-expressing GISTs.25 Despite the fact that exon 9 mutations are associated with a lower response rate, overall survival does not appear to be better with high-dose therapy. The investigators propose to conduct a retrospective analysis of mutational analysis on patients with GIST and determine the relationship between patient response and imatinib dose.


Eligibility: Inclusion Criteria:
  1. Histologic diagnosis of advanced stage or metastatic GIST
  2. Asian patient (as defined by the investigator)
  3. First line treatment with imatinib
  4. Availability of tumor samples for kit mutation analysis
  5. Availability of tumor response rate and or time to progression data
  Exclusion Criteria:

Relevance to patient case: not relevant
Patient case: 49-year-old female with Gastrointestinal stromal tumor. Genetic variant: KIT Exon 9 (A502_Y503dup). Other conditions: None.

Clinical trial: Phase II Study of Crenolanib (CP-868,596), for the Treatment of Patients With Advanced Gastrointestinal Stromal Tumors With the D842-related Mutations and Deletions in the PDGFRA Gene

Summary: This Phase II study is designed to evaluate the antitumor efficacy and pharmacokinetics of crenolanib (CP-868,596) in patients with D842-related mutant metastatic GIST.

Detailed description: Crenolanib (CP-868,596) is an orally bioavailable, selective inhibitor of PDGFR receptor tyrosine kinase with IC50s of 0.4 ng/mL and 0.8 ng/mL for PDGFRα and PDGFRβ, respectively.
  In preclinical models of cell lines with the D842V mutation in the PDGFRA gene, crenolanib (CP-868,596) blocked phosphorylation of PDGFRα at nanomolar concentrations, suggesting that it may provide a clinical benefit to patients with D842V mutant GIST.
  In addition, crenolanib was also active in inhibiting phosphorylation of cell lines with two point mutations (double mutants) PDGFRA V561D + D842V and PDGFRA T674I + D842V.

Eligibility: Inclusion Criteria
  -  Male or female, of any racial or ethnic group
  -  Age 18 years or older
  -  Life expectancy of greater than 12 weeks
  -  Patient able and willing to provide informed consent
  -  Normal liver function, defined as AST and ALT ≤2.5x ULN, and Total Bilirubin ≤ 2x ULN.
  -  Total creatinine ≤ 1.5x ULN
  -  ECOG Performance Status 0 - 2 (Appendix II)
  -  Patients must have histologically or cytologically confirmed GIST with a D842-related mutation or deletion on the PDGFRA gene
  -  Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan. See Section 10.1.2 for the evaluation of measurable disease.
  -  Patients must have recovered from any prior therapy and completed the minimum of, either 5 half-lives of prior therapy or 2 weeks must have elapsed since prior treatment
  Exclusion Criteria
  -  Patient unable to provide informed consent
  -  ECOG Performance status > 2
  -  Any concurrent anticancer therapy, immunotherapy, or hormonal therapy.
  -  Any other investigational agents taken within 2 weeks of start of study drug or if study drug will commence within 5 half-lives of prior therapy
  -  Patients with known or active Hepatitis B or C; liver cirrhosis.
  -  Patients with active fungal, viral, and bacterial infections
  -  Positive serum pregnancy test
  -  Pregnant or lactating women
  -  Patients on concomitant medications that induce or inhibit CYP3A4 (Appendix III)
  -  Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol e.g. impairment of gastrointestinal (GI) function, or GI disease that may significantly alter the absorption of the study drugs

Relevance to patient case: not relevant
Patient case: 49-year-old female with Gastrointestinal stromal tumor. Genetic variant: KIT Exon 9 (A502_Y503dup). Other conditions: None.

Clinical trial: WB-DWI for Early Prediction of Therapy Response in Patients With Advanced Metastatic GIST Treated With Regorafenib

Summary: The purpose of this study is to evaluate WB DWI as early predictor of response to treatment with regorafenib or placebo in patients with advanced metastatic GIST.

Detailed description: Aim of the study
  - To assess whole body diffusion-weighted magnetic resonance imaging (WB-DWI) for the assessment and early prediction of response of treatment with regorafenib or placebo in patients with advanced, metastatic gastro-intestinal stromal tumors (GIST)
  1. Evaluation of pretreatment apparent diffusion coefficient (ADC) and b1000 signal intensity (SI) of GIST visualized on the WB-DWI as predictor of time to progression, determined by progression-free survival (PFS)
  2. Evaluation of WB-DWI using changes of high b-value SI and ADC early during treatment (2weeks after start of therapy; allowed optimal window 10-14 days) as early predictor of time to progression or patient benefit according to RECIST (stable disease + partial response + complete response)
  3. Evaluation of WB-DWI for treatment follow-up 3 months after initiation of treatment. Confirmation of prior published pilot study (Dunet V et al, J Nucl Med 2010)
  4. Comparison of WB-DWI with conventional CT imaging for response assessment

Eligibility: Inclusion Criteria:
  -  patients with advanced, metastatic gastro-intestinal stromal tumors treated with regorafenib or placebo
  Exclusion Criteria:
  -  in case of a known contraindication for MRI (eg. pacemaker), the patient will not be admitted to the study

Relevance to patient case: not relevant
Patient case: 49-year-old female with Gastrointestinal stromal tumor. Genetic variant: KIT Exon 9 (A502_Y503dup). Other conditions: None.

Clinical trial: Treatment Response Evaluation in Gastrointestinal Stromal Tumor (GIST) Patients

Summary: The purpose of this study is to compare sensitivity, specificity and accuracy of PET, DW MRI and CT separately and combined for the evaluation of treatment response and progression-free survival in patients with GIST.


Eligibility: Inclusion Criteria:
  -  Metastatic GIST patients suitable for TKI treatment
  -  GIST patients pursuing preoperative neoadjuvant TKI treatment
  Exclusion Criteria:
  -  Patients with contraindications to MRI and/or TKI treatment. For patients with renal failure, CT without intravenous contrast will be performed according to clinical practice.
  -  Patients who do not sign the consent paper for any reason or do not accept the study premises or patients who wish to withdraw for any reason during the study

Relevance to patient case: not relevant
Patient case: 49-year-old female with Gastrointestinal stromal tumor. Genetic variant: KIT Exon 9 (A502_Y503dup). Other conditions: None.

Clinical trial: Efficacy of Nilotinib in Adult Patients With Gastrointestinal Stromal Tumors Resistant to Imatinib and Sunitinib.

Summary: This study will evaluate the preliminary efficacy of nilotinib in pretreated patients (Imatinib, Sunitinib) with unresectable or metastatic gastrointestinal stromal tumors.


Eligibility: Inclusion Criteria:
  -  Histologically confirmed diagnosis of GIST that is unresectable and/or metastatic and therefore not amenable to surgery or combined modality with curative intent.
  -  Radiologically confirmed disease progression during imatinib therapy at a dose of at least 400 mg daily and/or radiologically confirmed disease progression during sunitinib therapy OR documented intolerance to imatinib and/or sunitinib. (Patients with prior additional investigational treatment of GIST prior to study entry can be included.)
  -  At least one measurable site of disease on CT/MRI as defined by RECIST criteria.
  Exclusion Criteria:
  -  Prior treatment with nilotinib.
  -  Treatment with any cytotoxic and/or investigational cytotoxic drug ≤ 4 weeks (6 weeks for nitrosurea or mitomycin C) prior to Visit 1.
  -  Prior or concomitant malignancies requiring active treatment other than GIST with the exception of previous or concomitant basal cell skin cancer, previous cervical carcinoma in situ.
  -  Impaired cardiac function at visit 1
  -  Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol e.g. impairment of gastrointestinal (GI) function, or GI disease that may significantly alter the absorption of the study drugs, uncontrolled diabetes.
  Other protocol-defined inclusion/exclusion criteria may apply

Relevance to patient case: not relevant
Patient case: 49-year-old female with Gastrointestinal stromal tumor. Genetic variant: KIT Exon 9 (A502_Y503dup). Other conditions: None.

Clinical trial: A Study of Olaratumab (IMC-3G3) in Previously Treated Participants With Unresectable and/or Metastatic Gastrointestinal Stromal Tumors

Summary: The purpose of this study is to evaluate the tumor response of stable disease (SD), partial response (PR), or complete response (CR) [according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1 criteria)] at 12 weeks in participants with Gastrointestinal Stromal Tumors (GIST) harboring platelet-derived growth factor receptor alpha (PDGFRα) mutations and patients with GIST not harboring PDGFRα mutations.


Eligibility: Inclusion Criteria:
  -  Participant has histologically or cytologically confirmed, unresectable and/or metastatic GIST
  -  Participant has measurable disease
  -  Participant has documented objective progression following, or intolerance to, treatment with both imatinib and sunitinib
  -  Participant's Eastern Cooperative Oncology Group (ECOG) performance status (PS) is 0 to 2
  -  Participant has either:
  1. prior results from growth factor receptor associated with tyrosine kinase activity (KIT) and PDGFRα mutation analysis that meet analytical criteria as defined for the on-study analysis of these mutations and tumor tissue (from either primary or metastatic tumor) that can be submitted for analysis within 30 days after the first dose of study therapy; or
  2. if prior results from KIT and PDGFRα mutation analysis are not available or do not meet analytical criteria as above, then tumor tissue (from either primary or metastatic tumor) must be submitted for genotype testing at the latest 28 days prior to the first dose of study therapy
  -  Participant has adequate hematologic, hepatic, renal and coagulation function
  -  Women of childbearing potential and sexually active males must agree to use adequate contraception prior to study and for at least 12 weeks after the last dose of IMC-3G3
  -  Participant has a life expectancy of ≥ 3 months
  Exclusion Criteria:
  -  Participant has untreated central nervous system metastases, and as a result, is clinically unstable with regard to neurologic function
  -  Participant has a history of another primary cancer
  -  Participant has received any investigational therapy within 14 days prior to registration, or is currently enrolled in any other type of medical research
  -  Participant is receiving concurrent treatment with other anticancer therapy
  -  Participant has known human immunodeficiency virus (HIV) infection
  -  Participant has undergone major surgery within 28 days prior to registration
  -  If female, participant is pregnant or breastfeeding

Relevance to patient case: possibly relevant
Patient case: 49-year-old female with Gastrointestinal stromal tumor. Genetic variant: KIT Exon 9 (A502_Y503dup). Other conditions: None.

Clinical trial: A Study of Sunitinib In Young Patients With Advanced Gastrointestinal Stromal Tumor

Summary: Children and young adults with gastrointestinal stromal tumors (GIST) will be treated with sunitinib. The safety (including pharmacokinetics) and tolerability of sunitinib will be studied in these patients. In addition, tumor responses and overall survival will be assessed.


Eligibility: Inclusion Criteria:
  -  Histological diagnosis of GIST.
  -  Patients must have demonstrated either disease progression or intolerance to imatinib mesylate, have non-mutant Stem Cell Factor Receptor gene (KIT) GIST, or cannot obtain imatinib in their country
  -  Measurable by Response Evaluation Criterion in Solid Tumors (RECIST) or evaluable disease.
  Exclusion Criteria:
  -  Current treatment with another investigational agent.
  -  Prior sunitinib treatment.
  -  Prior therapy with known risk for cardiovascular complications.

Relevance to patient case: not relevant
Patient case: 49-year-old female with Gastrointestinal stromal tumor. Genetic variant: KIT Exon 9 (A502_Y503dup). Other conditions: None.

Clinical trial: Tissue Procurement for Gastric Cancer, Gastrointestinal Stromal Tumors (GIST), Esophageal Cancer, Pancreas Cancer, Hepatocellular Cancer, Biliary Cancer, Neuroendocrine, Peritoneal Mesothelioma, Anal Cancer and Colorectal Cancer in Patients Undergoing Surgery or Biopsy

Summary: The purpose of this study is to collect and store normal and malignant tissue from patients with gastric cancer, GIST, esophageal cancer, pancreas cancer, hepatocellular cancer, biliary cancer, neuroendocrine, peritoneal mesothelioma, anal cancer and colorectal cancer, an estimated 50 to 100 of each tumor type. To collect and store blood samples from patients with gastric cancer, GIST, esophageal cancer, pancreas cancer, hepatocellular cancer, biliary cancer, neuroendocrine, peritoneal mesothelioma, anal cancer and colorectal cancer. To create a database for the collected tissue and allow access to relevant clinical information for current and future protocols. To create tissue microarrays for each gastrointestinal cancer subtype, namely, gastric cancer, GIST, esophageal cancer, pancreas cancer, hepatocellular cancer, biliary cancer, neuroendocrine, peritoneal mesothelioma, anal cancer and colorectal cancer, to facilitate future molecular studies. To grant access to Dr Kindler, Dr. Salgia, and Dr. Catenacci to this database (as it is being acquired) of the coupled patient tissue samples (normal and malignant) and relevant clinical information for the investigation of tyrosine kinases, such as Met and Ron, receptor tyrosine kinase family members, STATs, paxillin, focal adhesion proteins, cell motility/migration proteins, tyrosine/serine/threonine kinase family members, related molecules, and downstream targets implicated in the pathogenesis of GI cancers. Examples of molecular testing include evaluation of DNA mutation, alternative splice variants, protein expression and phosphorylation, and immunohistochemistry on samples. These studies will be correlated with clinical information as stated above.


Eligibility: Inclusion Criteria:
  -  any patient diagnosed with Gastric (stomach) Cancer, Esophageal (foodpipe) Cancer, Pancreas Cancer, Liver Cancer, Biliary (gallbladder) Cancer, Gastrointestinal Stromal Tumor, Peritoneal Mesothelioma (cancer in the lining of the abdomen), Neuroendocrine (of or relating to the cells that release a hormone into the blood in response to a neural stimulus) Tumor, Anal Cancer or Colorectal Cancer cancer that requires you to undergo a surgical or diagnostic procedure.

Relevance to patient case: not relevant
Patient case: 49-year-old female with Gastrointestinal stromal tumor. Genetic variant: KIT Exon 9 (A502_Y503dup). Other conditions: None.

Clinical trial: Non-Interventional Retrospective Correlation Of Tumor Mutational Status To Clinical Benefit Of GIST Patients Treated With Sunitinib

Summary: Retrospective correlation of clinical outcomes data with mutational status in GIST subjects treated with sunitinib.

Detailed description: This is a non-interventional trial. No active patients will participate in this study. Only data generated from the A6181036 study will be utilized for correlational purposes. The A6181036 study data in addition to mutational status data previously analyzed but not collected as part of the A6181036 study in the same patient population

Eligibility: Inclusion Criteria:
  -  GIST subjects that participated in the A6181036 study that had mutational status data analyzed.
  Exclusion Criteria:
  -  Subjects not participating in the A6181036 study

Relevance to patient case: not relevant