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Recruiting NCT05661643

The Efficacy and Safety of Temozolomide in SDH-deficient GIST

Phase II Interventional Gastrointestinal Stromal Tumors

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Temozolomide capsule.
Who it may be relevant to
Registry conditions: Gastrointestinal Stromal Tumors. Basic parameters: from 20 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
South Korea
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

A Phase 2 Study to Evaluate the Efficacy and Safety of Temozolomide in Advanced Gastrointestinal Stromal Tumor Patients With SDH Deficiency

Overview

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

Detailed description

Wild type GISTs are less responsive to imatinib with a response rate of 23.1-44.6% and a median progressiion-free survival of 12.3-12.8 months. The efficacy of imatinib is limited in particular in SDH deficienctGIST with a reported response of 2%. Therefore, the development of a new therapeutic agents is urgently needed.

Recently, a study of TKI-resistant SDH-deficient preclinical model showed that temozolomide, an alkylating agent, promotes DNA damage in tumor cells, leading to tumor cell killing. In a retrospective analysis, 2 out of 5 SDH deficient GIST patients treated with temozolomide showed partial response, suggesting its efficacy in this patient population.

Based on these findings,The goal of this clinical trial is to investigate the efficacy and safety of temozolomide in SDH deficiency GIST patients. In addition, for exploratory purposes, aim to investigate the efficacy and safety of temozolomide in KIT and PDGFRA wild-type GIST without SDH deficiency.

Interventions

  • Drug Temozolomide capsule
    Temozolomide 200 mg/m2 is administered orally for 1-5 days of each cycle, and then canceled for 23 days (a total of 28 days is 1 cycle)

Primary outcome measures

  • Objective respone rate in SDH deficiency wild type GIST [Time frame: up to 4 years]

Eligibility criteria

Inclusion criteria

  • Age 20 years or older, at the time of acquisition of informed consent
  • Histologically confirmed GIST with CD117(+), DOG-1(+)
  • Wild type GIST without KIT or PDGFRα gene mutations determined by Sanger sequencing and panel sequencing
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 \~ 2
  • Resolution of all adverse events with prior treatments to grade 0 or 1 by NCI-CTCAE version 5.0
  • At least one measurable lesion by RECIST version 1.1.
  • Adequate bone marrow, hepatic, renal, and other organ functions, before adjuvant imatinib treatment
  • Neutrophil >1,500/mm3
  • Platelet > 100,000/mm3
  • Hemoglobin >8.0 g/dL
  • Total bilirubin < 1.5 x upper limit of normal (ULN)
  • AST/ALT < 2.5 x ULN
  • Creatinine <1.5 x ULN
  • Life expectancy ≥12 weeks
  • Disease 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 consent

Exclusion criteria

  • Confirmed GIST with KIT or PDGFRα gene mutations determined by Sanger sequencing and panel sequencing
  • Women of child-bearing potential who are pregnant or breast feeding
  • Women 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 administration
  • If 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 arrhythmia
  • Uncontrolled infection
  • Acute and chronic liver disease and all chronic liver impairment.(But Patients with stable chronic hepatitis B are eligible
  • Acute, or chronic medical or psychiatric condition or laboratory abnormality such as active uncontrolled infection that difficult to study participation in the judgment of the investigator
  • Known 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 disorder
  • The patients with NTRK fusion

5\)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
N/A
Model
Single group
Masking
Open label
Primary purpose
Treatment

Study locations

South Korea · 1 center
  • Asan Medical Center, University of Ulsan College of Medicine — Seoul

Identifiers

NCT: NCT05661643 · AMC2203

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗