Temozolomide in Treating Patients with Advanced SDH-Mutant Gastrointestinal Stromal Tumor
- Patient has the ability to understand and the willingness to sign a written informed consent
- Patient has pathologically confirmed GIST with loss of SDHB expression by immunohistochemistry and assessment of SDHA/B/C/D gene mutation(s) by next generation sequencing
- Patient has recurrent or refractory/unresectable or metastatic disease for which there is no known curative therapy. Patients with recurrent or progressive disease will be eligible. Newly diagnosed patients with resectable localized disease will not be eligible. Newly diagnosed patients with metastatic disease and newly diagnosed patients with residual tumor following surgical debulking will be eligible
- Prior therapy: * Prior therapy requirements: Because there are no standard therapy regimens known to be effective for SDH-mutant/deficient GIST, previously untreated participants are eligible. Patients previously treated with other therapies for GIST (i.e., imatinib, sunitinib, regorafenib, etc.) also will be eligible * Prior therapy wash-out period requirements: Patient has recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy ** Myelosuppressive chemotherapy: At least 3 weeks since completion ** Biologic (anti-neoplastic agent): At least 7 days since completion of therapy with a biologic agent * Radiation (XRT): >= 1 week must have elapsed from prior palliative XRT to non-target lesions
- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Absolute neutrophil count >= 1000/mm^3
- Platelet count >= 50,000/ mm^3 (transfusion independent for > 7 days)
- Hemoglobin >= 8.0 g/dL (may receive transfusions)
- Total bilirubin =< 2.0 x institution’s upper limit of normal (ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 5 x institutional ULN
- Albumin >= 2 g/dL
- Serum creatinine =< 1.5 x institutional ULN
- Creatinine clearance >= 30 ml/min
- 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. Note: Females of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
- 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 Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
- Life expectancy of > 12 weeks
- Patients who have had major surgery within 4 weeks of initiation of study medication
- 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 >= Common Terminology Criteria for Adverse Events (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 defined as: * Prior history of cardiovascular disease including heart failure that meets New York Heart Association (NYHA) 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 human immunodeficiency virus [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(s)
I. To determine overall response rate at 6 months for temozolomide (TMZ) therapy in patients with SDH-mutant/deficient gastrointestinal stromal tumor (GIST).
I. To determine progression-free survival.
II. To determine overall survival.
III. To determine safety and tolerability of TMZ.
I. To determine effect of TMZ therapy on serum succinate/fumarate ratio.
II. To determine effect of TMZ therapy on tumor metabolism.
Patients receive temozolomide orally (PO) daily on days 1-21. Cycles repeat every 28 days for 6 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 28 days and then every 3-6 months.
Trial Phase Phase II
Trial Type Treatment
UC San Diego Medical Center - Hillcrest
Adam Michael Burgoyne
- Primary ID 180114
- Secondary IDs NCI-2018-02492
- Clinicaltrials.gov ID NCT03556384