Temozolomide for treating SDH-deficient gastrointestinal stromal tumors

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

This study is testing if a drug called temozolomide can help people with a specific type of gastrointestinal stromal tumor that doesn't respond well to standard treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 29 (estimated)
• Ages: 20 Years and up
• Sex: All
• Sponsor: Asan Medical Center (Academic / other)
• Drugs / interventions: imatinib, Imitinib, sunitinib, chemotherapy
• Locations: 1 site (Seoul, Seoul)
• Trial ID: NCT05661643 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the efficacy and safety of temozolomide, an alkylating agent, in patients with SDH-deficient gastrointestinal stromal tumors (GIST). Given the limited response of these tumors to standard treatments like imatinib, the study seeks to determine if temozolomide can effectively promote tumor cell death. The trial will include patients with histologically confirmed GIST and will assess treatment outcomes based on measurable lesions. Additionally, it will explore the drug's effects on KIT and PDGFRA wild-type GISTs without SDH deficiency.

Who should consider this trial

Good fit: Ideal candidates include adults aged 20 and older with histologically confirmed SDH-deficient GIST who have experienced disease progression or intolerable toxicity from prior imatinib treatment.

Not a fit: Patients with GISTs that are not SDH-deficient or those who have not previously received imatinib may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with SDH-deficient GISTs, improving their outcomes.

How similar studies have performed: While temozolomide has shown promise in preclinical models and retrospective analyses, this approach is still relatively novel for treating SDH-deficient GISTs.

Eligibility criteria

Inclusion Criteria:

1. Age 20 years or older, at the time of acquisition of informed consent
2. Histologically confirmed GIST with CD117(+), DOG-1(+)
3. Wild type GIST without KIT or PDGFRα gene mutations determined by Sanger sequencing and panel sequencing
4. Eastern Cooperative Oncology Group (ECOG) performance status 0 \~ 2
5. Resolution of all adverse events with prior treatments to grade 0 or 1 by NCI-CTCAE version 5.0
6. At least one measurable lesion by RECIST version 1.1.
7. 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
8. Life expectancy ≥12 weeks
9. Disease progression or discontinuation of treatment due to intolerable toxicity at least with palliative 1st line imatinib .
10. 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.)
11. Provision of a signed written informed consent

Exclusion Criteria:

1. Confirmed GIST with KIT or PDGFRα gene mutations determined by Sanger sequencing and panel sequencing
2. Women of child-bearing potential who are pregnant or breast feeding
3. 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
4. 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
5. Uncontrolled infection
6. Acute and chronic liver disease and all chronic liver impairment.(But Patients with stable chronic hepatitis B are eligible
7. 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
8. Known diagnosis of HIV infection (HIV testing is not mandatory).
9. History of another primary malignancy that is currently clinically significant or currently requires active intervention.
10. Alcohol or substance abuse disorder
11. The patients with NTRK fusion

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Where this trial is running

Seoul, Seoul

• Asan Medical Center, University of Ulsan College of Medicine — Seoul, Seoul, South Korea (Recruiting)

Study contacts

• Study coordinator: Min-Hee Ryu, MD, PhD

Conditions Gastrointestinal Stromal Tumors