An Open-Label, Phase 2 Efficacy Study of Temozolomide (TMZ) In Advanced Succinate Dehydrogenase (SDH)-Mutant/Deficient Gastrointestinal Stromal Tumor (GIST)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 23
- 试验地点
- 5
- 主要终点
- Overall Response Rate
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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-
- •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.
排除标准
- •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
研究组 & 干预措施
TMZ 85 mg/m2 mg orally
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.
干预措施: Temozolomide (Drug)
结局指标
主要结局
Overall Response Rate
时间窗: 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.
次要结局
- Progression-free survival(4 years)
- Overall survival(4 years)
- Adverse events related to TMZ(6 months)
- Progression-free Survival(30 months)
- Overall Survival(40 months)
- Adverse Events and Serious Adverse Events(40 months)
研究者
Adam Burgoyne, MD, PhD
Associate Professor of Medicine
University of California, San Diego