A Phase I/II Trial Of STI571 In Children With Newly Diagnosed Poor Prognosis Brainstem Gliomas And Recurrent Intracranial Malignant Gliomas
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 85
- 试验地点
- 10
- 主要终点
- Number of Participants in Phase I Stratum I With Dose Limiting Toxicities (DLT) Observed During First 8 Weeks (Courses 1 and 2) of Imatinib Therapy
研究概览
简要总结
Phase I/II trial to estimate the maximum tolerated dose of imatinib mesylate in newly diagnosed brain stem gliomas and recurrent high grade gliomas and to assess the effectiveness of imatinib mesylate in treating young patients who have newly diagnosed intrinsic brain stem glioma. Imatinib mesylate may interfere with the growth of tumor cells by blocking the enzymes necessary for their growth. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining imatinib mesylate with radiation therapy may kill more tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose (MTD) of imatinib mesylate after completion of radiation in children with newly diagnosed poor prognosis brainstem gliomas. (Phase I, strata I closed to accrual as of 5/28/04.) II. Determine the maximum tolerated dose (MTD) of imatinib mesylate in children with recurrent high-grade intracranial glioma stratified according to the use of enzyme-inducing anticonvulsant drugs (EIACDs). (Phase I, strata IIA and IIB closed to accrual as of 8/15/03 and 8/15/04, respectively) III. Determine the safety and efficacy of this drug in patients with newly diagnosed diffuse intrinsic brainstem gliomas. (Phase II)
SECONDARY OBJECTIVES:
I. Explore neuroimaging and biological correlatives of therapeutic activity of this regimen in these patients. (Phase I, all strata closed to accrual as of 8/15/04) II. Determine the pharmacokinetics of these regimens in these patients overall and by enzyme-inducing anticonvulsant drugs (EIACDs) (Phase I, all strata closed to accrual as of 8/15/04.) III. Estimate the progression-free survival (PFS) and overall survival (OS) of newly diagnosed diffuse intrinsic brainstem gliomas treated with this drug. (Phase I and II)
OUTLINE: This is a phase I dose-escalation, multicenter study followed by a phase II. Patients are stratified according to tumor type (newly diagnosed intrinsic brainstem glioma vs recurrent/refractory intracranial high-grade glioma). Patients in stratum II (phase I only) are further stratified according to concurrent use of enzyme-inducing anticonvulsant drugs (EIACDs) (yes vs no). Patients are assigned to one of three strata in the phase I study.
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
- 3 Years 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Imatinib mesylate
干预措施: imatinib mesylate (Drug)
Imatinib mesylate
干预措施: local irradiation therapy (Radiation)
结局指标
主要结局
Number of Participants in Phase I Stratum I With Dose Limiting Toxicities (DLT) Observed During First 8 Weeks (Courses 1 and 2) of Imatinib Therapy
时间窗: Day 1 of Imatinib Mesylate Therapy to Week 8
The dose limiting toxicity (DLT) analysis population consists of phase I stratum I participants who developed DLT during the maximum tolerated dose (MTD) estimation period (course 1 and 2) or who completed the MTD estimation period (courses 1 and 2) without DLTs. DLTs observed during courses 1 and 2 were used to estimate the MTD. The estimated MTD based on the 23 participants who either had a DLT during course 1 or 2 or completed courses 1 and 2 without DLT is 265 mg/m2/day.
Number of Participants in Phase I Stratum II With Dose Limiting Toxicities (DLT) Observed During First 8 Weeks (Courses 1 and 2) of Imatinib Therapy
时间窗: Day 1 of Imatinib Mesylate Therapy to Week 8
The dose limiting toxicity (DLT) analysis population consisted of phase I stratum II participants who developed DLT during the maximum tolerated dose (MTD) estimation period (courses 1 and 2) or who completed the MTD estimation period (courses 1 and 2) without DLTs. DLTs observed during courses 1 and 2 were used to estimate the MTD. The estimated MTD based on the DLT analysis population of 20 in stratum IIA was 465 mg/m2/day. An MTD was not established in stratum IIB as no DLTs were observed at the higher dose levels of 620 and 800 mg/m2/day.
Median Progression-free Survival (PFS)
时间窗: Assessed pre-radiation, before the first dose of imatinib, and then every 8 weeks
Progression-free survival is defined as the interval from initiation of treatment to the earliest of disease progression (tumor increase of 25% over baseline tumor measurement; appearance of new lesion(s); or progressive/worsening neurological status) or death for patients who failed, or to the last date of follow up for patients without failure.
次要结局
- Change From Baseline in Volume FLAIR at Two Weeks After Completion of Radiation(Baseline and two weeks post completion of radiation)
- Peak Concentration (Cmax)(Day 1 of Course 1)
- Median Overall Survival(Assessed before radiation therapy, before the first dose of imatinib, then every 8 weeks.)
- Pre-treatment Basic Fibroblast Growth Factor Values From Urine(Pre-treatment)
- Pre-treatment Basic Fibroblast Growth Factor Values From Plasma(Pre-treatment)
- Pre-treatment Vascular Endothelial Growth Factor From Urine(Pre-treatment)
- Pre-treatment Vascular Endothelial Growth Factor Values From Plasma(Pre-treatment)