A Cancer Research UK Phase I Trial of Olaparib (AZD2281), an Oral PARP Inhibitor, in Combination With Extended Low-Dose Oral Temozolomide in Patients With Relapsed Glioblastoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 34
- 试验地点
- 11
- 主要终点
- Detection of olaparib in tumor tissue using liquid chromatography mass spectrometry (LC-MS) seen in at least 1 out of the 6 patients treated in stage 1 of the study
研究概览
简要总结
RATIONALE: Olaparib 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. Olaparib may help temozolomide kill more tumor cells by making tumor cells more sensitive to the drug.
PURPOSE: This phase I trial is studying the side effects and best dose of olaparib and temozolomide in treating patients with relapsed glioblastoma.
详细描述
OBJECTIVES:
Primary
- To determine whether olaparib crosses the blood-brain barrier (BBB) and achieves tumor penetration in patients with relapsed glioblastoma. (Stage 1)
- To determine the safety and tolerability of the combination of olaparib and temozolomide in patients with relapsed glioblastoma. (Stage 2)
Secondary
- To assess BBB disruption and BBB permeability in patients with relapsed glioblastoma. (Stage 1 and stage 2 maximum-tolerated dose [MTD] expansion cohort)
- To assess the possible anti-tumor activity of the combination of olaparib and temozolomide in patients with relapsed glioblastoma. (Stage 2)
研究设计
- 研究类型
- Interventional
- 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
Detection of olaparib in tumor tissue using liquid chromatography mass spectrometry (LC-MS) seen in at least 1 out of the 6 patients treated in stage 1 of the study
Maximum-tolerated dose of olaparib in combination with temozolomide (stage 2)
Toxicity profile and dose-limiting toxicity as assessed by NCI CTCAE Version 4.02 (stage 2)
次要结局
- Measurement of blood-brain barrier (BBB) disruption and permeability biomarkers by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) (stage 1 and stage 2 MTD expansion cohort)
- Progression-free survival at 6 months post-surgery as assessed by the Response Assessment in Neuro-Oncology Working Group (RANO) criteria from conventional MRI and clinical assessment (stage 2)