A Phase I Study of AZD2281 in Combination With Irinotecan in Patients With Locally Advanced or Metastatic Incurable Colorectal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 4
- 主要终点
- Dose-limiting toxicities
研究概览
简要总结
RATIONALE: AZD2281 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving AZD2281 together with irinotecan may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of AZD2281 and irinotecan in treating patients with locally advanced or metastatic colorectal cancer.
详细描述
OBJECTIVES:
- To determine the recommended phase II dose of AZD2281 and irinotecan hydrochloride in patients with locally advanced or metastatic colorectal cancer.
- To determine the safety, tolerability, toxicity profile, dose-limiting toxicities, and pharmacokinetic profile of this regimen.
- To assess the correlation, if any, between the toxicity profile and pharmacokinetics of this regimen.
- To assess, preliminarily, the antitumor activity of this regimen in patients with measurable disease.
- To demonstrate the pharmacodynamic activity of this regimen by establishing its effects in tumor biopsies, cheek swabs, and blood samples.
- To assess the correlation, if any, between patients with tumors demonstrating microsatellite instability and antitumor activity and pharmacodynamic effects of this regimen.
- To investigate the impact of common genetic polymorphisms of genes of relevant pathways (drug metabolism, DNA repair, and apoptosis) on outcome and toxicity as well as other pharmacodynamic effects.
OUTLINE: This is a multicenter, dose-escalation study of AZD2281 and irinotecan hydrochloride.
- Part I: Patients receive oral AZD2281 twice a day on days -7 to 21 in course 1 and on days 1-21 in all subsequent courses. Patients also receive irinotecan hydrochloride IV over 90 minutes on day 1. Courses repeat every 21 days (course 1 is 28 days) until the maximum tolerated dose is determined in the absence of disease progression or unacceptable toxicity.
- Part II: Patients then receive oral AZD2281 once daily on days 1-5 and irinotecan hydrochloride IV over 90 minutes on day 3 at the maximum tolerated dose determined in Part I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Patients undergo cheek swabs, tumor tissue, and blood sample collection periodically for pharmacokinetic, pharmacodynamic, and correlative studies.
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 70 Years（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
Dose-limiting toxicities
时间窗: 2011-May-28
Fatigue, Nausea, Dehydration and Anorexia.
Pharmacokinetic profile
时间窗: Nov 2011
End of study
Correlation, if any, between the toxicity profile and pharmacokinetics
时间窗: Nov 2011
End of study.
Recommended phase II dose of AZD2281 and irinotecan hydrochloride
时间窗: Nov 2011
End of study
Safety
时间窗: Nov 2011
End of study
Tolerability
时间窗: Nov 2011
End of study
次要结局
- Efficacy(Nov 2011)
- Pharmacodynamic outcomes(Nov 2011)