araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 56-year-old female with gastrointestinal stromal tumor; genetic feature: PDGFRA (D842V)

Clinical trial: A Study Evaluating STA-9090 in Patients With Metastatic and/or Unresectable Gastrointestinal Stromal Tumor (GIST)

Summary: The purpose of this study is to determine if STA-9090 is effective in the treatment of patients with metastatic and/or unresectable GIST.

Detailed description: Planned:
  -  Stage 1: 23 patients. If ≥4 patients had clinical benefit, an additional 32 patients were to be enrolled. Up to 3 additional patients with platelet-derived growth factor receptor, alpha polypeptide (PDGFRA) mutation were to be enrolled, regardless of the total study enrollment.
  -  Stage 2: 55 patients. Progressing to this stage was dependent on Stage 1 results.
  Analyzed:
  -  Stage 1: 27 patients were enrolled and analyzed. The study was not expanded to Stage 2 due to insufficient efficacy.

Eligibility: Inclusion Criteria:
  -  Must be at least 18 years of age at the time of study entry
  -  Must have histologically confirmed metastatic and/or unresectable GIST
  -  Must have measurable disease on computed tomography or magnetic resonance imaging as defined by Response Evaluation Criteria in Solid Tumors (RECIST)
  -  Must have documented failure (due to either progression or intolerance)of at least prior imatinib and sunitinib. Previous administration of other known heat shock protein 90 (Hsp90) inhibitors is permitted
  -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  -  Must have acceptable laboratory values as defined in the protocol
  Exclusion Criteria:
  -  Known central nervous system metastases
  -  Major surgery within 4 weeks prior to receiving STA-9090
  -  Use of any investigational agents within 2 weeks or 6 half-lives of the agent, whichever is shorter prior to receiving STA-9090
  -  No treatment with chronic immunosuppressants
  -  Must have otherwise adequate health status as defined in the protocol
  -  Left ventricular ejection fraction (LVEF) < than or = 50% at baseline
  -  Baseline corrected QT interval (QTc) > 470 msec
  -  Pregnant or lactating females

Relevance to patient case: possibly relevant
Patient case: 56-year-old female with gastrointestinal stromal tumor; genetic feature: PDGFRA (D842V)

Clinical trial: Post Marketing Surveillance On The Safety And Tolerability Of Sunitinib Malate (Sutent) For Filipino Patients

Summary: The primary purpose is to monitor the safety and tolerability and effectiveness of sunitinib malate in the treatment of patients with metastatic renal cell carcinoma and gastrointestinal stromal tumor among filipino patients in usual clinical practice setting.

Detailed description: Open label

Eligibility: Inclusion Criteria:
  -  Age 18 years and above
  -  Diagnosed with metastatic renal cell carcinoma or gastrointestinal stromal tumor after imatinib treatment failure or intolerance
  Exclusion Criteria:
  -  Subjects with conditions that are contraindicated with sunitinib malate

Relevance to patient case: not relevant
Patient case: 56-year-old female with gastrointestinal stromal tumor; genetic feature: PDGFRA (D842V)

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: 56-year-old female with gastrointestinal stromal tumor; genetic feature: PDGFRA (D842V)

Clinical trial: Study of Crenolanib for the Treatment of Patients With Advanced GIST 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: definitely relevant
Patient case: 56-year-old female with gastrointestinal stromal tumor; genetic feature: PDGFRA (D842V)

Clinical trial: Everolimus in Combination With Imatinib in Patients With Glivec Refractory/Resistant Gastrointestinal Stromal Tumors

Summary: This trial was a Phase I/II, non-randomized, open label, multi-center study, following a sequential 2- part design. The first part, Phase I, was designed to assess whether there is a pharmacokinetic interaction between Glivec/Gleevec (imatinib) and RAD001(everolimus) as well as to collect safety data when these two drugs are co-administered. The second part, (Phase II), was designed to assess the potential efficacy of the combination in imatinib-resistant GIST patients in two strata of patients:
  -  Patients resistant to imatinib as first-line drug therapy and in whom the maximum tolerated dose was at least 600 mg/d (Stratum 1, first-line resistant/refractory)
  -  Patients resistant to imatinib as well as to post-imatinib drug therapy (Stratum 2, post second-line therapy).


Eligibility: Inclusion Criteria:
  Phase l:
  -  Patients aged ≥ 18 years
  -  Patients with a histologically proven diagnosis of GIST and clinical evidence of resistance to imatinib despite at least 4 months continuous treatment with imatinib
  -  Patients with at least 2 months at a dosage of ≥ 600 mg/day (progression despite uninterrupted therapy for 2 months at ≥800 mg/d for patients entering the Phase I cohort investigating the 800 mg/d dose)
  -  Patients were to have at least one measurable lesion (longest diameter ≥20 mm on conventional CT or MRI scan
  -  patients were to have ≥10 mm on spiral CT) and were to have a WHO Performance Status Score ≤ 2.
  -  Patients also were to have adequate bone marrow, liver and renal function on imatinib treatment, as specified in the protocol
  Phase ll:
  • For Phase II (Stratum 2) patients must have progression on other 2nd line drug therapies following prior progression on imatinib (Stratum 2)
  Exclusion Criteria:
  -  Women who are pregnant or breast-feeding
  -  Patients presenting with known or symptomatic CNS metastases or leptomeningeal involvement
  -  Patients with any concurrent major medical condition liable to compromise the patient's participation in the study (e.g. known HIV infection, uncontrolled diabetes, serious cardiac dysrhythmia or condition, New York Heart Association classification of III or IV, congestive cardiac failure, myocardial infarction with 6 months, unstable angina, chronic or acute renal or liver disease, uncontrolled infections including abscess or fistulae, etc.)
  -  Patients with a history of another malignancy within 5 years prior to study entry, except curatively treated non-melanotic skin cancer or in-situ cervical cancer
  -  Patients unwilling to or unable to comply with the protocol
  -  Patients who are receiving glucocorticoids (only if the p70s6 kinase1 assay is being performed), since these have been shown to inhibit p70s6 kinase1 activity.
  Other protocol-defined inclusion/exclusion criteria may apply

Relevance to patient case: not relevant
Patient case: 56-year-old female with gastrointestinal stromal tumor; genetic feature: PDGFRA (D842V)

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: 56-year-old female with gastrointestinal stromal tumor; genetic feature: PDGFRA (D842V)

Clinical trial: Endoscopic Submucosal Dissection Registry

Summary: The purpose of this study is to monitor the success rates and completion rates for endoscopic submucosal dissection (ESD) for gastrointestinal (GI) cancers.


Eligibility: Inclusion Criteria: Patients referred for endoscopic treatment of advanced gastrointestinal (colorectal, gastric, duodenal, esophagus) neoplasia, defined by any of the following procedures:
  1. Flat dysplastic lesion greater than 2cm(IIa or IIb by Paris classification)
  2. Flat depressed lesion < 2cm in size (llc by Paris Classification)
  3. Ulcerated lesion < 2cm (Paris type lll) staged as T1N0 on endoscopic ultrasound
  4. Upon resection, the criteria for curative ESD include:
  -  Non-invasive neoplasia of differentiated carcinoma
  -  No lymphovascular invasion
  -  Intramucosal cancer or minute submucosal cancer <1 mm invasion (sm1)
  -  Negative deep and lateral margins.
  Exclusion Criteria:
  1. Use of antiplatelet(e.g. clopidrogel) or anticoagulation (e.g. Coumadin) agents that cannot be withheld for at least 7 days prior to the procedure. Aspirin use is accepted according to the American Society for Gastrointestinal Endoscopy for these procedures.
  2. Patients who refuse or who are unable to consent.
  3. Suboptimal colon prep, or solid gastric residual that precludes safe lesion resection at the time of endoscopy.
  4. Lesion location in a segment of the colon not conducive to ESD, including significant narrowing, tortuosity and/or extensive diverticular disease, as determined by the endoscopist.

Relevance to patient case: not relevant
Patient case: 56-year-old female with gastrointestinal stromal tumor; genetic feature: PDGFRA (D842V)

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: 56-year-old female with gastrointestinal stromal tumor; genetic feature: PDGFRA (D842V)

Clinical trial: Detection of CF-DNA in Patients With Gastrointestinal Stromal Tumors (GIST)

Summary: Activating mutations of the kinases CKIT or PDGFRA can be detected in 90% of cases by DNA sequence analysis of a pathological specimen. These mutated genomic DNA fragments are highly specific for the tumor and are released by the tumor into the circulation. Allele-specific PCR can be used to specifically amplify and quantify mutated CKIT and PDGFR DNA fragments.
  The current trial aims to evaluate whether tumor DNA carrying mutations for CKIT and PDGFRA can be detected and quantified in the plasma of patients with active GIST, and whether detection can be correlated with the clinical course of disease either under therapy or in progressive disease irrespective of current therapy.


Eligibility: Inclusion Criteria:
  -  Signed written informed consent
  -  Male or female patients aged >= 18 years
  -  Histologically confirmed GIST
  -  Known activating mutation of CKIT or PDGFRA and tissue sample can be provided for central mutation analysis or mutation status unknown and tissue sample can be provided for central mutation analysis at baseline
  -  Routinely planned follow-up visits in no longer than three months intervals (+ 14 days) including local standard of care diagnostic imaging (CT, PET- CT, or MRI)
  -  At least one GIST lesion that can be measured by CT, PET-CT, or MRI
  -  Planned surgery of one or more disease manifestations or planned TKI treatment (such as imatinib or sunitinib) in neoadjuvant or palliative intention or disease progression irrespective of current/planned treatment
  -  Life expectancy of at least three months
  Exclusion Criteria:
  -  Wild type sequence for CKIT exon 9, 11, 13, 14, 17, 18 and PDGFRA exon 18
  -  Tissue sample can not be provided for central mutation analysis
  -  Surgery of primary or progressive lesions already completed and currently no evidence of progressive lesions
  -  Patients currently receiving adjuvant TKI treatment after surgery and no evidence of progressive lesions
  -  Patients currently receiving palliative TKI treatment and no evidence of progressive lesions
  -  Planned follow-up intervals including CT, PET-CT or MRI at more than three months intervals (+ 14 days)
  -  Coexisting medical condition or treatment that could interfere with the ability of the patient to comply with planned treatment interventions (surgery or TKI treatment) or regular follow-up visits
  -  Patients unwilling to or unable to comply with the planned therapeutic intervention (surgery or TKI treatment) or to comply with the regular follow-up visits including blood sample collection
  -  Pregnancy and lactation
  -  Presence of chronic inflammatory diseases, autoimmune diseases, or liver cirrhosis
  -  Known HIV and/or hepatitis B or C infection
  -  Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix and basal or squamous cell carcinoma of the skin

Relevance to patient case: possibly relevant
Patient case: 56-year-old female with gastrointestinal stromal tumor; genetic feature: PDGFRA (D842V)

Clinical trial: Efficacy and Safety of Dovitinib in Patients With Gastrointestinal Stromal Tumors Refractory and/or Intolerant to Imatinib

Summary: The purpose of this study is to evaluate the efficacy and safety of Dovitinib in patients with gastrointestinal stromal tumors refractory and/or intolerant to Imatinib


Eligibility: Inclusion Criteria:
  -  Histologically confirmed GIST of any anatomical location, which is 1) unresectable and/ or metastatic with documented disease progression while on therapy with imatinib or 2) surgically removed localized GIST, recurrent on adjuvant imatinib or recurrent within the first 3 months after discontinuation of adjuvant imatinib or 3) patients with unresectable and/or metastatic GIST intolerant to imatinib
  -  Positive immunohistochemical staining for c-KIT (CD117); or negative staining for KIT, but with either positive staining for DOG1 or an identified mutation of KIT or PDGFRA gene
  -  Documented disease progression according to RECIST (version 1.1) on prior therapy with imatinib at a dose of at least 400mg/day or patients with unresectable and/or metastatic GIST who are intolerant to imatinib
  -  At least one measurable GIST lesion according to RECIST (version 1.1).
  -  Adequate bone marrow, liver and renal function
  Exclusion Criteria:
  -  Patients who have received any other tyrosine-kinase inhibitor but imatinib for GIST
  -  Patients who received cytotoxic drugs ≤ 4 weeks prior to starting Dovitinib (TKI258)
  -  Patients who are treated or planned to be treated concomitantly with other cytotoxic or antineoplastic treatments, such as chemotherapy, immunotherapy, biological response modifiers, or radiotherapy
  -  Patients with another primary malignancy within 3 years prior to starting the study drug
  -  Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic) ≤ 4 weeks prior to starting Dovitinib (TKI258) or who have not recovered from the adverse effects of such therapy
  -  Patients with a history of pulmonary embolism (PE), or untreated deep venous thrombosis (DVT) within the past 6 months
  -  Patients with impaired cardiac function or clinically significant cardiac diseases
  -  Patients with impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of Dovitinib
  -  Patients with prior complete gastrectomy
  -  Patients with brain metastasis or history of brain metastasis
  -  Patients who are currently receiving anticoagulation treatment with therapeutic doses of warfarin or equivalent anticoagulant
  -  Pregnant or breast-feeding women
  Other protocol-defined inclusion/exclusion criteria may apply.

Relevance to patient case: possibly relevant