A Phase I/II Trial of Cloretazine® (VNP40101M) and Temodar® (Temozolomide) for Patients With Malignant Glioma in First Relapse or Progression
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 14
- 试验地点
- 4
- 主要终点
- MTD of CLORETAZINE
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as temozolomide and VNP40101M, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Temozolomide may also stop the growth of tumor cells by blocking blood flow to the tumor.
PURPOSE: This phase I/II trial is studying the side effects and best dose of VNP40101M when given together with temozolomide and to see how well it works in treating patients with progressive or relapsed malignant glioma.
详细描述
OBJECTIVES:
- To determine the maximum tolerated dose (MTD) of VNP40101M when administered with temozolomide in patients with progressive or relapsed (first relapse) malignant glioma. (Phase I)
- To record the toxicities of VNP40101M when administered with temozolomide. (Phase I and II)
- To measure the level of AGT expression in peripheral blood monocytes before treatment with temozolomide and just prior to the administration of VNP40101M. (Phase I and II)
- To determine MGMT methylation status as well as other methylation patterns in blood and tissue from patients treated with this regimen and correlate with outcome. (Phase I and II)
- To determine the 6- and 12-month progression-free survival rates of patients treated with this regimen. (Phase II)
- To determine overall survival of patients treated with this regimen. (Phase II)
- To determine the complete and partial response rates in patients treated with this regimen. (Phase II)
- To determine CSF penetration of VNP40101M once the MTD is reached from phase I and correlate with serum/plasma pharmacokinetics. (Phase II)
OUTLINE:
- Phase I: Patients receive oral temozolomide on days 1-7 and VNP40101M IV over 15-30 minutes 2 hours after the last dose of temozolomide on day 7. Treatment repeats every 7 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of VNP40101M until the maximum tolerated dose (MTD) 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
- 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
- 未提供
排除标准
- 未提供
结局指标
主要结局
MTD of CLORETAZINE
时间窗: At the end of phase one
To determine the MTD of CLORETAZINE when administered with Temodar® in patients with malignant gliomas in first or second relapse
Progression-free survival rate
时间窗: End of Phase II
To determine the 6 and 12 month progression-free survival rate.
次要结局
- Toxicities of CLORETAZINE when administered with Temodar®.(Adverse events are monitored at screening/baseline;day one; termination visit; followup until death.)
- Response rate to CLORETAZINE after Temodar® in patients with malignant gliomas in first or second relapse(Day one of every cycle)
- Record the toxicities of CLORETAZINE when administered after Temodar(Continuously after the first dose;within thirty days of each administration of investigational agent)
- MGMT Methylation Status(Baseline and day seven of every cycle)
- Determine overall survival(All patients will be followed until death)
- Measure the level of AGT expression(Day seven of every cycle)
- CSF penetration of CLORETAZINE(Day seven of cycle one of Phase 2 only)