A Dose Finding and Safety/Efficacy Trial of CPT-11 (Irinotecan) in Patients With Recurrent Malignant Gliomas
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 试验地点
- 18
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.
PURPOSE: Phase I/II trial to study the effectiveness of irinotecan in treating patients with recurrent malignant glioma.
详细描述
OBJECTIVES: I. Determine the maximum tolerated dose of intravenous irinotecan when administered weekly for 4 weeks in patients with recurrent malignant gliomas. II. Describe the pharmacokinetics of this route of administration, measuring both irinotecan and the active metabolite SN-38, and determine the effects of hepatic enzyme inducing drugs, such as anticonvulsants, on the pharmacokinetics in these patients. III. Determine preliminary response data and activity of irinotecan in this patient population. IV. Correlate response with topoisomerase I levels in brain tumor tissue from patients undergoing treatment.
OUTLINE: Patients are stratified based on their use/kind of anticonvulsant drugs. This stratification yields two arms for this study. Arm I consists of patients who use anticonvulsant drugs that induce hepatic metabolic enzymes. Arm II consists of patients who use anticonvulsant drugs that cause modest to no induction of hepatic metabolic enzymes or no anticonvulsant drug. Three patients in each arm receive irinotecan by 90-minute IV infusions every week for 4 weeks, followed by a 2 week rest period. The dose is escalated for the next cohort of 3 patients in the absence of unacceptable dose limiting toxicity. The 6 week course is repeated until unacceptable toxicity or disease progression. Once the maximum tolerated dose has been established for each arm, additional patients are treated at that dose level. Patients are followed every 2 months.
PROJECTED ACCRUAL: A minimum of 3 patients will be accrued into the phase I portion of the study and a total of 18-35 patients will be accrued into each arm of the phase II portion of the study.
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 that is progressive or recurrent following radiation therapy or chemotherapy Anaplastic astrocytoma Glioblastoma multiforme Low grade glioma that has progressed to biopsy proven high grade glioma is eligible if the progression occurred after radiotherapy with or without chemotherapy Measurable progression or recurrence by serial MR or CT imaging
- •PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: Greater than 2 months Hematopoietic: Absolute neutrophil count 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.5 mg/dL Transaminases no greater than 4 times upper limit of normal Renal: Creatinine no greater than 1.7 mg/dL Cardiovascular: No uncontrolled hypertension No angina pectoris No evidence of uncontrolled cardiac dysrhythmia Other: No serious infection or other medical illness No other prior or concurrent malignancy within 5 years except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix and breast Not pregnant or nursing Adequate contraception required of all fertile patients
- •PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior topoisomerase 1 inhibitor (topotecan, irinotecan, 9- aminocamptothecin) No more that 1 prior chemotherapy regimen At least 6 weeks since nitrosourea and recovered At least 3 weeks since any other chemotherapy and recovered Endocrine therapy: Not specified Radiotherapy: At least 3 months since completion of most recent course of radiotherapy and recovered Surgery: Not specified Other: No concurrent investigational agents At least 14 days since prior valproic acid No concurrent valproic acid
排除标准
- 未提供