A Phase I Study of Imatinib Mesylate in Combination With Temozolomide in Patients With Malignant Glioma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 65
- 试验地点
- 2
- 主要终点
- Anti-tumor activity
研究概览
简要总结
RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving imatinib mesylate together with temozolomide may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of imatinib mesylate when given together with temozolomide in treating patients with malignant glioma.
详细描述
OBJECTIVES:
- Determine the maximum tolerated dose and dose-limiting toxicity, if attainable, of imatinib mesylate in combination with temozolomide in patients with malignant glioma.
- Characterize the safety and tolerability of imatinib mesylate, including acute and chronic toxicities, in these patients.
- Determine the effect of temozolomide on the pharmacokinetics (PK) of imatinib mesylate at each dose level.
- Evaluate the impact of enzyme-inducing anti-epileptic drug (EIAED) coadministration on the PK of imatinib mesylate using a population-based PK approach.
- Evaluate the antitumor activity of imatinib mesylate plus temozolomide.
OUTLINE: This is a dose-escalation study of imatinib mesylate. Patients are stratified according to concurrent enzyme-inducing anticonvulsants (e.g., phenytoin, phenobarbital, carbamazepine, fosphenytoin, primidone, oxcarbazepine) (yes vs no).
Patients receive oral imatinib mesylate once or twice daily on days 1-8 and oral temozolomide once daily on days 4-8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of patients receive escalating doses of imatinib mesylate until the maximum tolerated dose is determined.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
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
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed malignant glioma
- •Any of the following subtypes:
- •Glioblastoma multiforme
- •Gliosarcoma
- •Anaplastic astrocytoma
- •Anaplastic oligodendroglioma
- •Anaplastic oligoastrocytoma
- •Previous histologic diagnosis of a lower grade of glioma allowed if there is histologic evidence of progression to a diagnosis of malignant glioma
- •Multifocal disease allowed
- •Must have undergone prior conventional external-beam radiation therapy
- •Stable disease, disease recurrence, or relapsed disease
- •Must not have received any systemic therapy for this recurrence or relapse
- •No prior progressive disease
- •No central/systemic fluid collections (pericardial effusion, pulmonary effusion, ascites) ≥ grade 2
- •No evidence of intratumor hemorrhage on pretreatment diagnostic imaging, except for stable post-operative grade 1 hemorrhage
- •PATIENT CHARACTERISTICS:
- •Karnofsky performance status 70-100%
- •Absolute neutrophil count > 1,500/mm³
- •Hemoglobin > 9 g/dL
- •Platelet count > 100,000/mm³
- •AST and ALT < 2.5 times upper limit of normal (ULN)
- •Bilirubin < 1.5 times ULN
- •Creatinine < 1.5 times ULN
- •No chronic renal disease
- •No active uncontrolled infection
- •No uncontrolled diabetes
- •No excessive risk of bleeding, as defined by occurrence of any of the following:
- •Stroke within the past 6 months
- •History of CNS or intraocular bleed
- •Septic endocarditis
- •No history of labile hypertension
- •No congestive heart failure
- •No poorly controlled hypertension
- •No myocardial infarction within the past 6 months
- •No history of poor compliance with antihypertensive regimen
- •No other severe and/or uncontrolled medical disease that would preclude study participation
- •No peripheral edema ≥ grade 2
- •No gastrointestinal bleeding
- •No gross hematuria
- •No other active systemic bleeding
- •Patients must not have experienced toxicity ≥ grade 3 with prior treatment with either temozolomide or imatinib mesylate
- •No other primary malignancy within the past 5 years except basal cell skin cancer or carcinoma in situ of the cervix or other cancer not currently clinically significant nor requiring active interventions
- •PRIOR CONCURRENT THERAPY:
- •See Disease Characteristics
- •Recovered from all prior therapy
- •Prior surgical resection(s) allowed
- •At least 2 weeks since prior surgery
- •At least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas)
- •At least 2 weeks since prior external-beam radiotherapy
- 另有 3 项未显示
排除标准
- 未提供
结局指标
主要结局
Anti-tumor activity
Maximum tolerated dose
Dose-limiting toxicity
Safety and tolerability
Pharmacokinetics
次要结局
未报告次要终点