Gastrointestinal Stromal TumorsPhase 2NCT03556384
Temozolomide (TMZ) In Advanced Succinate Dehydrogenase (SDH)-Mutant/Deficient Gastrointestinal Stromal Tumor (GIST)
A Phase 2 study testing Temozolomide in people with Gastrointestinal Stromal Tumors and Sdh, run by Adam Burgoyne, MD, PhD at 4 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastrointestinal Stromal Tumors, Sdh, GIST
- What is being tested?
- Temozolomide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 4 sitesUnited States
- Study dates
- 12 Sep 2018to 19 Nov 2024
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient has pathologically confirmed SDH-mutant/deficient GIST.
- Has recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy.
- Patient has an ECOG Performance Status of 0-2.
- Patient has adequate hematologic, hepatic and renal function.
- Female patient of childbearing potential has a negative serum or urine pregnancy within 72 hours prior to receiving the first dose of study medication.
- 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.
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- 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.
- Has measurable or evaluable disease as per RECIST v1.1 (Appendix B).
- Life expectancy of >12 weeks.
Who cannot join
- Patients who have had major surgery within 4 weeks of initiation of study medication.
- Patients who are receiving other concurrent anti-neoplastic therapy (e.g., chemotherapy, targeted therapy, immunotherapy, or radiotherapy) at the start of study treatment.
- 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.
- Evidence of severe or uncontrolled systemic diseases [e.g., unstable or uncompensated respiratory, cardiac (including life threatening arrhythmias)].
- 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.
- 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.
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- Pregnant or breast-feeding females.
- 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.
- 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.
- Patients who cannot swallow oral formulations of the agent
Trial locations and contacts
4 sites in 1 country.
United States4 sites
UC San Diego Moores Cancer Center
La Jolla, California, 92093
University of Miami
Miami, Florida, 33136
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Oregon Health & Science University
Portland, Oregon, 97239
About this study
Official title: An Open-Label, Phase 2 Efficacy Study of Temozolomide (TMZ) In Advanced Succinate Dehydrogenase (SDH)-Mutant/Deficient Gastrointestinal Stromal Tumor (GIST)
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.
Read more
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.
Read the 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.
- Conditions
- Gastrointestinal Stromal Tumors, Sdh, GIST, Cancer
- Being tested
- Temozolomide
- Keywords
- cancer, Temozolomide, GIST, SDH-Mutant/Deficient, SDH, Succinate Dehydrogenase
- Medical subject headings
- Gastrointestinal Stromal Tumors, Hematoma, Subdural, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TemozolomideDrug
Also called TEMODAR®
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 group | Role | What they receive |
|---|---|---|
| TMZ 85 mg/m2 mg orally | Experimental | TMZ 85 mg/m2 mg orally once 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. 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 after the last dose of study drug. Patients discontinuing study treatment will be followed every 3-6 months for disease recurrence and survival. Receives: Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate
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.
Measured: 6 months
Secondary outcomes (3)
Progression-free Survival
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.
Measured: 30 months
Overall Survival
Number of participants alive
Measured: 40 months
Adverse Events and Serious Adverse Events
Number of participants with adverse events and serious adverse events
Measured: 40 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2018
- Study start12 Sep 2018
- Primary completion22 Jun 2023
- Study completion19 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Gastrointestinal Stromal TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Adam Burgoyne, MD, PhD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Adam Burgoyne, MD, PhD, University of California, San Diego
- Investigators
- Adam Burgoyne, MD, PhD, Principal investigator, University of California, San DiegoJason Sicklick, MD, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03556384
- Sponsor's protocol ID
- 180114
- Other IDs
- FD-R-6334
- Status last verified
- Jul 2026
- First submitted
- 1 Jun 2018
- Last updated
- 28 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No