The Efficacy and Safety of Temozolomide in SDH-deficient GIST

The goal of this clinical trial is to investigate the efficacy and safety of temozolomide in SDH deficiency GIST patients.

Inclusion Criteria:Age 20 years or older, at the time of acquisition of informed consentHistologically confirmed GIST with CD117(+), DOG-1(+)Wild type GIST without KIT or PDGFRα gene mutations determined by Sanger sequencing and panel sequencingEastern Cooperative Oncology Group (ECOG) performance status 0 ~ 2Resolution of all adverse events with prior treatments to grade 0 or 1 by NCI-CTCAE version 5.0At least one measurable lesion by RECIST version 1.1.Adequate bone marrow, hepatic, renal, and other organ functions, before adjuvant imatinib treatmentNeutrophil >1,500/mm3Platelet > 100,000/mm3Hemoglobin >8.0 g/dLTotal bilirubin < 1.5 x upper limit of normal (ULN)AST/ALT < 2.5 x ULNCreatinine <1.5 x ULNLife expectancy ≥12 weeksDisease progression or discontinuation of treatment due to intolerable toxicity at least with palliative 1st line imatinib .Washout period of previous TKIs or chemotherapy for more than 4 times the half life ((Imitinib and regorafenib need 1 week and sunitinib need 2 weeks.)Provision of a signed written informed consentExclusion Criteria:Confirmed GIST with KIT or PDGFRα gene mutations determined by Sanger sequencing and panel sequencingWomen of child-bearing potential who are pregnant or breast feedingWomen or men who are not willing to use effective contraception entering the study period or until at least 6 months after the last study drug administrationIf any of the following applies within ≤ 6 months prior to starting study enrollment : Myocardial Infarction, severe instable angina, coronary/peripheral bypass, NYHA class III or IV congestive heart failure, stroke or transient ischemic attack, treatment required severe arrhythmiaUncontrolled infectionAcute and chronic liver disease and all chronic liver impairment.(But Patients with stable chronic hepatitis B are eligibleAcute, or chronic medical or psychiatric condition or laboratory abnormality such as active uncontrolled infection that difficult to study participation in the judgment of the investigatorKnown diagnosis of HIV infection (HIV testing is not mandatory).History of another primary malignancy that is currently clinically significant or currently requires active intervention.Alcohol or substance abuse disorderThe patients with NTRK fusion5)