Temozolomide (TMZ) In Advanced Succinate Dehydrogenase (SDH)-Mutant/Deficient Gastrointestinal Stromal Tumor (GIST)

An Open-Label, Phase 2 Efficacy Study of Temozolomide (TMZ) In Advanced Succinate Dehydrogenase (SDH)-Mutant/Deficient Gastrointestinal Stromal Tumor (GIST)

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03556384

Enrollment

Registered

2018-06-14

Start date

2018-09-12

Completion date

2024-11-19

Last updated

2026-07-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cancer, Gastrointestinal Stromal Tumors, GIST, Sdh

Keywords

cancer, Temozolomide, GIST, SDH-Mutant/Deficient, SDH, Succinate Dehydrogenase

Brief summary

Funding Source - FDA OOPD FDA-approved products for patients with unresectable or metastatic GIST include therapies such as imatinib and sunitinib. Although there are FDA-approved products for the treatment of advanced/metastatic GIST, these therapies are known to be ineffective in the SDH-mutant/deficient subtype and no known effective therapies exist. The purpose of this study is to investigate SDH-Mutant/Deficient Gastrointestinal Stromal cancer's response to the drug Temozolomide (TMZ) and aim to improve patient outcomes. Temozolomide is approved by the FDA for the treatment of newly diagnosed glioblastoma multiforme (GBM) and refractory anaplastic astrocytoma cancers. Temozolomide is considered experimental because it is not approved by the FDA for the treatment of SDH-Mutant/Deficient Gastrointestinal Stromal Tumor.

Detailed description

This oncology study will be a phase 2 study for patients with advanced or metastatic GIST. This study will determine overall response rate at 6 months for TMZ therapy in patients with SDH-mutant/deficient GIST. Treatment will continue for 6 months (with option to continue if benefiting treatment) or until disease progression or unacceptable toxicity (whichever occurs first). All patients will have regular evaluations for assessment of safety parameters. Temozolomide dose may be held and/or modified for the management of adverse treatment effects according to pre-specified criteria. Patients will have radiographic imaging (CT or MRI) every 8 weeks to assess tumor resection. An end of treatment visit for clinical evaluations and safety assessments will be performed approximately 28 days (7 days) after the last dose of study drug. Patients discontinuing study treatment will be followed every 3-6 months for disease recurrence and survival.

Interventions

DRUGTemozolomide

Temozolomide 85 mg/m2 will be administered orally for 21 days followed by 7 days without treatment in 28 day cycles. Treatment will continue for 6 months (with option to continue if benefiting treatment) or until disease progression or unacceptable toxicity (whichever occurs first). All patients will have regular evaluations for assessment of safety parameters

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Patient has pathologically confirmed SDH-mutant/deficient GIST. 2. Has recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy. 3. Patient has an ECOG Performance Status of 0-2. 4. Patient has adequate hematologic, hepatic and renal function. 5. Female patient of childbearing potential has a negative serum or urine pregnancy within 72 hours prior to receiving the first dose of study medication. 6. Female patient of childbearing potential agrees to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. 7. Male patient with a partner of childbearing potential agrees to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. 8. Has measurable or evaluable disease as per RECIST v1.1 (Appendix B). 9. Life expectancy of \>12 weeks.

Exclusion criteria

1. Patients who have had major surgery within 4 weeks of initiation of study medication. 2. Patients who are receiving other concurrent anti-neoplastic therapy (e.g., chemotherapy, targeted therapy, immunotherapy, or radiotherapy) at the start of study treatment. 3. Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. 4. Evidence of severe or uncontrolled systemic diseases \[e.g., unstable or uncompensated respiratory, cardiac (including life threatening arrhythmias)\]. 5. Unresolved toxicity ≥ CTCAE Grade 2 from previous anti-cancer therapy except alopecia (if applicable) unless agreed that the patient can be entered after discussion with the Medical Monitor. 6. Presence of cardiac impairment class III and IV definitions; OR history of myocardial infarction/active ischemic heart disease within one year of study entry; OR uncontrolled dysrhythmias; OR poorly controlled angina. 7. Pregnant or breast-feeding females. 8. Medical condition such as uncontrolled infection (including HIV), uncontrolled diabetes mellitus or cardiac disease which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient. 9. Any concurrent condition which in the investigator's opinion makes it undesirable for the subject to participate in this trial or which would jeopardize compliance with the protocol. 10. Patients who cannot swallow oral formulations of the agent

Design outcomes

Primary

Measure	Time frame	Description
Overall Response Rate	6 months	To determine overall response rate at 6 months for TMZ therapy in patients with SDH-mutant/deficient GIST. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Secondary

Measure	Time frame	Description
Progression-free Survival	30 months	Progression-free survival. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Overall Survival	40 months	Number of participants alive
Adverse Events and Serious Adverse Events	40 months	Number of participants with adverse events and serious adverse events

Countries

United States

Contacts

PRINCIPAL_INVESTIGATORAdam Burgoyne, MD, PhD

University of California, San Diego

PRINCIPAL_INVESTIGATORJason Sicklick, MD