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

Clinical trial: Study on the Evolution of Genes Mutation Related With Gastrointestinal Stromal Tumors

Summary: Mutations of tumor-related genes are dynamic. Gastrointestinal stromal tumor cells often are obviously more invasive in case of recurrence. The great majority of relapses may be associated with secondary mutation in the GIST related genes. Full gene sequences of c-KIT、PDGFRA and DOG1, which is extracted from the specimen cells of repeated surgical resection or biopsy tissue in GIST patients with postoperative recurrence, are analyzed with the screening-sequencing approach, in order to investigate the characteristics and variations associated with the different gene mutations of c-KIT、PDGFRA and DOG1 in GIST patients and be likely to find out the evolutionary pattern, try to learn the facts about the effect of tyrosine kinase inhibitors on the GIST related genes, make a survey of any association of c-KIT、PDGFRA and DOG1 gene mutations and provide the basis for seeking molecular marker of GIST for monitoring course of disease, and offer a theoretical basis and new therapeutic strategies for application of clinical treatment.


Eligibility: Inclusion Criteria:
  -  patients with Gist at the Department of Gastrointestinal and Glands Surgery of the First Affiliated Hospital of Guangxi Medical University in China.
  Exclusion Criteria:
  -  patients with hepatitis and tuberculosis

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

Clinical trial: Pazopanib in Advanced Gastrointestinal Stromal Tumors Refractory to Imatinib and Sunitinib

Summary: Patients with metastatic or locally advanced gastrointestinal stromal tumors (GIST) who develop resistance against the two hitherto approved drugs for this disease, the tyrosin kinase inhibitors (TKIs) imatinib and sunitinib, have a poor prognosis. Sometimes a further response may be achieved by other drugs, mainly other TKIs, which have been explored in different studies but not yet have been approved for clinical use. Pazopanib is a TKI inhibiting the tyrosin kinases KIT, PDGFRA, and VEGF 1-3, all of which have important roles in the pathogenesis of GIST. Theoretically, it may function in GIST, and it deserves investigational trials. The drug is approved for metastatic renal cancer and is relatively well tolerated. In this trial (SSG XXI), the disease control rate (DCR) = (CR+PR+SD) after 12 weeks of treatment will be assessed as the primary endpoint, and at the same time trough levels will be measured. Secondary endpoints include ORR, PFS, toxicity, and disease control rate in relation to trough level week 12 and in relation to the primary mutation of the tumor (if known). The goal is to include 72 patients in the trial, which is open and single arm.


Eligibility: Eligibility Criteria:
  -  Metastatic and/or locally advanced GIST, with diagnosis based on histology with positive c-kit and/or DOG-1, or with a GIST-typical mutation in KIT or PDGFR
  -  Measurable disease on CT (computed tomography) as defined by RECIST criteria; at least one measurable lesion not given radiotherapy
  -  History of progressive disease on CT according to RECIST criteria after both imatinib and sunitinib treatment, and also after nilotinib if this drug has been given
  -  No other TKIs given than imatinib, sunitinib and nilotinib
  -  Age at least 18 years at the time of diagnosis of GIST
  -  WHO performance status 0-2
  -  Resolution of all toxic side effects from earlier TKI treatment and any other potential non-TKI treatment to grade 1 or below
  -  Sufficient organ functions as defined in the protocol
  -  Absence of earlier or present certain other conditions as defined in the protocol
  -  No pregnancy or lactation
  -  Women with childbearing potential must accept the use of adequate contraception throughout the study period
  -  Written informed consent

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

Clinical trial: Continuation of Drug Supply in Chinese Patients After CAMN107DBR01study Termination

Summary: Continuation of drug supply in Chinese patients after CAMN107DBR01study termination.

Detailed description: Five patients who are on treatment of imatinib and deriving clinical benefit after CAMN107DBR01 study termination and written informed consent obtained will enter the trial, all five patients will receive Glivec (8oomg per day) treatment until tumor progression [by RECIST guidelines, version 1.0], unacceptable toxicity, death or withdrawal of consent.

Eligibility: Inclusion Criteria:
  -  Five patients who are on treatment of imatinib and deriving clinical benefit after CAMN107DBR01 study termination and written informed consent obtained.
  Exclusion Criteria:
  -  N/A.

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

Clinical trial: Clinical Trial of Group ACYW135 Meningococcal Polysaccharide Vaccine 001

Summary: The clinical trial was designed to evaluate the safety against Group ACYW135 Meningococcal Polysaccharide Vaccine of Hualan administered on subjects 2 years of age and older.

Detailed description: Complying with requirements of the approval letter of clinical trial issued by SFDA (Approval Letter No.: 2006L01017), Hualan conducted phase I clinical trial of Group ACYW135 Meningococcal Polysaccharide Vaccine. The safety end points were the presence of any systemic, local and adverse reaction.

Eligibility: Inclusion Criteria:
  -  Healthy permanent residence 2 years of age and older, the subjects (or their guardians) are able to understand and sign the informed consent;
  -  Healthy male or female by oral history, physical examination and clinical judgment and who complies with vaccination of this product;
  -  Be able to comply with the requirements of clinical trial protocol and immunogenicity examination;
  -  Have no history of vaccination within the past 3 months and vaccination with other products within the last 2 weeks;
  -  Axillary temperature ≤37.0℃.
  Exclusion Criteria:
  -  Any acute disease, such as: tumor, autoimmunity disease, progressive atherosclerotic disease or diabetes with complication, chronic obstructive pulmonary disease need oxygen uptake, acute or progressive hepatopathy or nephropathy, congestive heart-failure, etc.;
  -  Allergic to vaccines or drugs (history of allergy to any vaccine in the past);
  -  History of neurologic symptom or signs;
  -  Known or suspected (or high risk) impaired or abnormal immune function, e.g.: receive immunosuppressant or immunopotentiator therapy, take immunoglobulin or blood product or plasma extract (except the gastrointestinal tract) within the past 3 months, HIV infection or related disease, etc.;
  -  History of meningitis infection or vaccination of meningococcal vaccine within the past 3 months;
  -  History of receiving other vaccines or immunoglobulin injection or any research drugs;
  -  Any acute disease needing application of antibiotics or anti-virus treatment in the whole body within the past 1 week;
  -  History of fever within the past 3 days (axillary temperature ≥38.0℃);
  -  Participating in another clinical trial;
  -  History of allergy, eclampsia, epilepsy, encephalopathy and mental disease or family disease;
  -  Thrombopenia or other coagulopathy that may cause contraindication to intramuscular injection;
  -  Acute chronic disease (such as Down syndrome, diabetes, sickle cell anemia or neurologic disease, Guillain-Barre Syndrome);
  -  Known or suspected diseases, including: respiratory system disease, acute infection or active stage of chronic disease, SBAV infection of children or mothers, cardiovascular disease, acute hypertension, cancer treatment, skin disease, etc.;
  -  Pregnancy;
  -  Any condition that, in the judgment of investigator, may affect trial assessment.

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

Clinical trial: Trial to Assess the Efficacy of Midostaurin (PKC412) in Patients With c-KIT or FLT3-ITD Mutated t(8;21) AML

Summary: To assess the efficacy of tyrosine-kinase inhibitor midostaurin in c-KIT or FLT3-ITD mutated t(8;21) AML. To assess the efficacy of midostaurin depending on the type of c-KIT mutation

Detailed description: AML patients displaying t(8;21) have a relatively favourable outcome. Nevertheless, only approximately 50% of patients carrying this cytogenetic aberration are alive at 5 years. This suggests that some patients have more aggressive leukemic phenotypes and indicates the need for treatment optimization with novel therapies.
  The mutated KIT gene as well as the FLT3-ITD mutation have recently been identified as factors most likely to explain the heterogeneous clinical outcomes within the group of t(8;21) AML. The FLT3 and c-KIT genes encode type III receptor tyrosine kinases (RTK) with important and partly redundant functions in early hematopoietic stem cells. Various activating mutations have been described for both genes. For c-KIT, the incidence ranges from 17 to 48% depending on the source population and type of mutations determined. It has been consistently shown that in AMLs with t(8;21), mutated c-KIT is associated with a dramatically increased risk of relapse and reduced overall survival compared to their unmutated counterparts. The FLT3-ITD mutation has a similar negative effect on prognosis in the patient group of t(8;21) mutated AMLs as c-KIT.
  PKC412 (midostaurin) is known to inhibit the c-KIT RTK activity as well as the FLT3 kinase, both in patients with ITD and TKD mutations. It should therefore be possible to abrogate the negative impact of pathologically increased c-KIT or FLT3-ITD activity on relapse and overall survival by using midostaurin in this patient population. Aim of the proposed clinical trial is to prove the efficacy of midostaurin in c-KIT or FLT3-ITD mutated t(8;21)- AMLs in an open-label one-arm design.

Eligibility: Inclusion Criteria:
  -  Diagnosis of c-KIT mutated t(8;21) AML i.e.
  1. >20% myeloid blasts in bone marrow and/or peripheral blood at initial diagnosis
  2. Plus cytogenetic diagnosis of aberration t(8;21)/AML1-ETO
  3. Plus mutation of c-KIT gene (mut-KIT17 or mut-KIT8) or FLT3-ITD mutation or both c-KIT and FLT3-ITD mutations
  -  Chemoresponsive disease as determined by early bone marrow assessment on day 14-16 after first cycle of induction therapy with cytarabine in combination with daunorubicine or idarubicine, or mitoxantrone- Fit for further intensive chemotherapy
  -  Age 18-65 years
  -  ECOG performance status of 0-2
  -  Life expectancy of at least 12 weeks
  Exclusion Criteria:
  -  Primary refractory or previously relapsed AML
  -  Non-eligibility for high-dose cytarabine based consolidation, e.g. intolerance to cytarabine
  -  Inability to swallow oral medications
  -  Symptomatic congestive heart failure
  -  Bilirubin >2.5 x upper limit of normal

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

Clinical trial: Regorafenib Post-marketing Surveillance in Japan

Summary: The objective of this study is to assess safety and effectiveness of Regorafenib using in real clinical practice

Detailed description: This study is a regulatory post-marketing surveillance in Japan, and it is a local prospective and observational study of patients who have received Regorafenib for gastrointestinal stromal tumors progressed after cancer chemotherapy.
  A total of 135 patients are to be enrolled and assessed in 6 months standard observational period. At 12 months and 24 months after the first administration of Regorafenib for confirmation of efficacy information including treatment duration and survival status of the patient.

Eligibility: Inclusion Criteria:
  -  Patients who are treated with Regorafenib/ STIVARGA and meet the product label.
  Exclusion Criteria:
  -  Patients who are treated with Regorafenib/ STIVARGA and don't meet the product label.

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

Clinical trial: Study of Oral RXDX-101 in Adult Patients With Locally Advanced or Metastatic Cancer Targeting NTRK1, NTRK2, NTRK3, ROS1, or ALK Molecular Alterations.

Summary: Entrectinib (RXDX-101) is an orally available inhibitor of the tyrosine kinases TrkA (coded by the gene NTRK1), TrkB (coded by the gene NTRK2), TrkC (coded by the gene NTRK3), ROS1 (coded by the gene ROS1), and ALK (coded by the gene ALK). Molecular alterations to one or more of these targets are present in several different tumor types, including non-small cell lung cancer (NSCLC), colorectal cancer (CRC), prostate cancer, papillary thyroid cancer, pancreatic cancer, and neuroblastoma. Patients with locally advanced or metastatic cancer with a detectable molecular alteration in targets of interest may be eligible for enrollment.
  Phase 1 will assess safety and tolerability of entrectinib via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and efficacy will be assessed in the dose expansion portion of the study.


Eligibility: Key Inclusion Criteria:
  -  Histologically or cytologically confirmed diagnosis of locally advanced or metastatic solid tumors that have a NTRK1, NTRK2, NTRK3, ROS1, or ALK molecular alteration.
  -  Measurable disease according to RECIST version 1.1.
  -  Prior cancer therapy is allowed, including crizotinib, ceritinib, and investigational drugs.
  -  Prior radiotherapy is allowed
  -  Patients with controlled asymptomatic central nervous system involvement are allowed.
  -  Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1.
  -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2.
  -  Adult patients age 18 years or older.
  -  Life expectancy of at least 3 months.
  Key Exclusion Criteria:
  -  Current participation in another therapeutic clinical trial.
  -  Prior treatment with entrectinib.
  -  History of prolonged QTc interval (e.g., repeated demonstration of a QTc interval > 450 milliseconds).
  -  History of additional risk factors for torsade de pointes (e.g., family history of long QT syndrome).
  -  Known active infections (bacterial, fungal, viral including HIV positivity).
  -  Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact on drug absorption.
  -  Known interstitial lung disease, interstitial fibrosis, or history of tyrosine kinase inhibitor-induced pneumonitis.
  -  Peripheral neuropathy ≥ Grade 2.

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

Clinical trial: The Oncopanel Pilot (TOP) Study

Summary: The BCCA Oncopanel is a clinical assay being developed to determine genotype status of a prospectively defined set of genes.
  The purpose of this pilot study is to assess the feasibility and effect on clinical-decision-making of the Oncopanel test. Eligible patients are those with advanced lung, colorectal, melanoma and GIST cancers and patients with diagnosed malignancies being considered for clinical trials.

Detailed description: Somatic mutations in solid tumors represent an established means of characterizing malignancies for prognostic, diagnostic and therapeutic purposes. Mutations in EGFR, KRAS, BRAF, and KIT and PDGFRA genes direct therapy in patients with advanced lung, colorectal, melanoma, and GIST tumors, respectively. Known or novel mutations in other genes may also be of clinical significance but are not identified by current genotyping offered to BC Cancer Agency (BCCA) patients. Furthermore, numerous candidate genes have been implicated as potential prognostic and predictive biomarkers in patients with solid tumours. As such, the Oncopanel is a clinical assay being developed to determine genotype status of a prospectively defined set of genes. The following clinically relevant set of genes and exons are included in the Oncpanel: KRAS, EGFR, BRAF, NRAS and HRAS, PIK3CA Signal Transduction Pathway Genes, RAS-RAF-MEK-MAPK Pathway, HER2, IDH1 and IDH2, ALK, TP53, c-KIT, STAT1&3 and PDGFRA. Additional testing on the tumour material will also include analysis of specific gene variants associated with adverse events or response to therapy.
  Numerous studies have documented the presence of circulating tumour DNA (ctDNA) among patients with advanced and early stage malignancies (20-22). The ability to diagnose standard cancer mutations with a blood-based assay (a "liquid biopsy") has not yet been established but presents obvious advantages. The emergence of "resistance" mutations arising in the metastatic tumor or throughout the course of therapy is well documented (21, 22). A blood biopsy may represent more accurate determination of the tumor's genetic features than archival DNA specimen. Adequate tissue specimens can be difficult to obtain from some patients with diagnosed malignancies, particularly lung cancer. A blood biopsy may represent a less invasive and timelier means of diagnosing both standard and translational cancer mutations.

Eligibility: Patients with archival tumor tissue and a known history of invasive malignancies are eligible if they meet one or more of the following criteria:
  -  Advanced colorectal cancer and eligible for standard KRAS testing,
  -  Advanced non-small cell lung cancer and eligible for standard EGFR testing,
  -  Advanced melanoma and eligible for standard BRAF testing,
  -  Gastrointestinal stromal tumors (GISTs) eligible for standard c-KIT and PDGFRA testing,
  -  Being considered for potential eligibility in clinical trial.

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

Clinical trial: Phase 1/1b Study of MGCD516 in Patients With Advanced Cancer

Summary: MGCD516 is a receptor tyrosine kinase (RTK) inhibitor shown in preclinical models to inhibit a closely related spectrum of RTKs including MET, AXL, MER, and members of the VEGFR, PDGFR, DDR2, TRK and Eph families. In this study, MGCD516 is orally administered to patients with advanced solid tumor malignancies to evaluate its safety, pharmacokinetic, metabolism, pharmacodynamic and clinical activity profiles.
  During the Phase 1 segment, the dose and regimen of MGCD516 will be assessed; during the Phase 1b segment, the clinical activity of MGCD516 will be evaluated in selected patient populations.
  Patients anticipated to be enrolled in Phase 1b will be selected based upon having a tumor type, including but not limited to, non small cell lung cancer and head and neck cancer positive for specific activating MET, NTRK2, NTRK3, or DDR2 mutations, MET or KIT/PDGFRA/KDR gene amplification, selected gene rearrangements involving the MET, RET, AXL, NTRK1, or NTRK3 gene loci, or having loss of function mutations in the CBL gene. In addition patients with clear cell renal cell carcinoma refractory to angiogenesis inhibitors or metastatic prostate cancer with bone metastasis will be enrolled.

Detailed description: During the Phase 1 segment, the dose and regimen of MGCD516 will be assessed.
  During the Phase 1b segment, the clinical activity of MGCD516 will be evaluated in selected patient populations. Patients anticipated to be enrolled in Phase 1b will be selected based upon the following cancer diagnosis:
  Non-small cell lung cancer with genetic alterations in MET, AXL, RET, TRK, DDR2, KDR, PDGFRA, KIT or CBL.
  Head and neck squamous cell carcinoma with genetic alterations in MET.
  Clear cell renal cell carcinoma refractory to angiogenesis inhibitors.
  Metastatic prostate cancer with bone metastases.
  Other cancer diagnosis having a selected genetic alteration in MGCD516 target RTKs.

Eligibility: Inclusion Criteria:
  -  Metastatic or unresectable solid tumor malignancy
  -  Standard treatment is not available
  -  Adequate bone marrow and organ function
  Exclusion Criteria:
  -  History of a significant cardiovascular illness
  -  Prolonged corrected QT (QTc) interval
  -  Left ventricular ejection fraction < 40%
  -  Symptomatic or uncontrolled brain metastases
  -  Other active cancer

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

Clinical trial: Prospective Cohort Study of the Clinical Applications for the Pathologic Type, Staging, and Grading of GIST

Summary: Evaluate the reliability of morphology standards for GIST pathologic type, staging and grading by retrospective analyzing clinical data; on this basis, establish a GIST standardized and individualized treatment mode to maximum benefit GIST patients, avoid under- and over-treatment.

Detailed description: 1. Retrospective analysis of GIST cases in the recent five years: the GIST clinical data of Fudan University Zhongshan Hospital from 2007 January to 2012 December were collected. By reviewing the HE slides, GIST was evaluated by 12 indicators, NIH scheme and WHO standard. Accomplish the gene sequencing of KIT, PDGFRA, B-raf, and SDH. Follow up the patients about their treatment and prognosis. Analyze and compare the advantages and disadvantages of the histomorphology indicators, NIH scheme, and WHO standard.
  2. Organize the first prospective cohort study of GIST individualized treatment based on the histomorphology. Obtain the evidence of histological assessment for GIST by following up patients for 3 years.
  3. Establish an evaluation criteria based on the morphology of GIST. Make objective evaluations about GIST tumor size, tumor location and gene mutation status in the prognosis estimate. Make rules to effectively guide individualized treatment of GIST.

Eligibility: All patients pathologically diagnosed with GIST during the period from 2013 to 2015

Relevance to patient case: possibly relevant