Pediatric Phase I and Pharmacokinetic Study of Irinotecan
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 试验地点
- 2
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 trial to study the effectiveness of irinotecan in treating children who have refractory or progressive solid tumors.
详细描述
OBJECTIVES:
- Determine the maximum tolerated dose and dose-limiting toxicity of irinotecan in children with refractory or progressive solid tumors.
- Determine the pharmacokinetics of this drug and its metabolites (SN-38, SN-38G, and APC) administered with and without concurrent anticonvulsants in this patient population.
- Determine the benefit this drug offers this patient population.
OUTLINE: This is a dose-escalation, multicenter study. Patients are accrued into stratum 1 initially and into stratum 2 if stratum 1 closes due to dose-limiting toxicity of myelosuppression or diarrhea. Patients on anticonvulsants will be accrued into stratum 3 and must meet the eligibility criteria for the stratum that is open (stratum 1 or stratum 2). (Stratum 1 closed as of 2002-09-15).
Patients receive irinotecan IV over 90 minutes weekly for 4 weeks. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of irinotecan until the maximum tolerated dose (MTD) with and without anticonvulsants is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
入排标准
- 年龄范围
- 1 Year 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically or cytologically confirmed solid tumor refractory to standard therapy or for which no known effective therapy exists
- •Brain tumors eligible
- •Histologic verification waived for brain stem gliomas
- •Evaluable disease
- •No bone marrow involvement
- •PATIENT CHARACTERISTICS:
- •Performance status:
- •Karnofsky 50-100% (over age 10)
- •Lansky 50-100% (age 10 and under)
- •Life expectancy:
- •At least 8 weeks
- •Hematopoietic:
- •Absolute neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •Hemoglobin at least 8 g/dL
- •Bilirubin less than 1.5 mg/dL
- •SGPT less than 5 times normal
- •Creatinine normal OR
- •Glomerular filtration rate at least 70 mL/min
- •No uncontrolled infection
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for 6 months after study
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy:
- •At least 6 months since prior autologous bone marrow transplantation (BMT) (not including stem cell rescue after high-dose chemotherapy)
- •At least 1 week since prior growth factors
- •No prior BMT with total body irradiation (stratum I)
- •No prior BMT with or without total body irradiation (stratum 2)
- •No prior allogeneic BMT (all strata)
- •No concurrent sargramostim (GM-CSF)
- •No other concurrent prophylactic growth factor support during the first course of therapy
- •Chemotherapy:
- •At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas)
- •No prior irinotecan
- •No more than 2 prior multi-agent chemotherapy regimens (stratum 2)
- •No other concurrent chemotherapy
- •Endocrine therapy:
- •Concurrent dexamethasone allowed if on stable or decreasing dose for at least 2 weeks prior to study
- •Radiotherapy:
- •At least 6 months since prior craniospinal radiotherapy or radiotherapy to 50% or more of the pelvis
- •At least 6 weeks since other prior substantial bone marrow radiotherapy
- •No prior central axis radiotherapy, pelvic radiotherapy, and/or total abdominal radiotherapy (stratum 2)
- •Not specified
- •Recovered from all prior therapy
- •No other concurrent investigational agents
- •Concurrent enzyme-inducing anticonvulsants (e.g., phenytoin, phenobarbital, carbamazepine) allowed if on stable dose for at least 2 weeks prior to study (stratum 3)
- •Concurrent valproic acid allowed if combined with another enzyme inducing anticonvulsant drug (stratum 3)
排除标准
- 未提供