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

NCT03556384 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 180114FD-R-6334
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 4

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.

Conditions

Gastrointestinal Stromal Tumors; Sdh; GIST; Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  To determine overall response rate at 6 months for TMZ therapy in patients with SDH-mutant/deficient GIST

  6 months

Secondary Outcomes (3)

• Progression-free survival

  4 years

• Overall survival

  4 years

• Adverse events related to TMZ

  6 months

Study Arms (1)

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.

Drug: Temozolomide

Interventions

Temozolomide DRUG

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

Also known as: TEMODAR®

TMZ 85 mg/m2 mg orally

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Adam Burgoyne, MD, PhD: lead

Study Sites (4)

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors; Hematoma, Subdural; Neoplasms

Interventions

Temozolomide

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intracranial Hemorrhage, Traumatic; Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Vascular Diseases; Cardiovascular Diseases; Hematoma; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Adam Burgoyne, MD, PhD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

• Jason Sicklick, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: June 1, 2018
• First Posted: June 14, 2018
• Study Start: September 12, 2018
• Primary Completion: June 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: November 4, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)