Phase I Study of the Pharmacokinetics and Pharmacodynamics of ZD6474 in Combination With Docetaxel in Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Pharmacodynamic parameters (percent inhibition of pERK, pKDR, and pEGFR)
研究概览
简要总结
RATIONALE: Vandetanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving vandetanib together with docetaxel may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of vandetanib given together with docetaxel in treating patients with advanced solid tumors.
详细描述
OBJECTIVES:
Primary
- To investigate the differential biological effects in tumor tissues through pharmacodynamic endpoints (percent inhibition of pERK, pKDR, and pEGFR) and their correlation with pharmacokinetics of vandetanib in combination with docetaxel in patients with advanced solid tumors.
- To correlate the pharmacodynamic endpoints with the pharmacokinetics of this combination regimen in these patients.
- To recommend an optimal biological dose of this combination regimen for further testing.
Secondary
- To correlate the pharmacokinetics with safety profiles of two dose levels of vandetanib when given in combination with docetaxel.
- To investigate scientific correlates, including serum proteomics and microvessel density (CD31) and cell death (TUNEL) using tumor tissue biopsy samples taken at baseline and during treatment.
- To determine the objective response in patients with measurable disease at baseline.
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 120 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
研究组 & 干预措施
Arm 1
vandetanib and docetaxel
干预措施: docetaxel (Drug)
Arm 1
vandetanib and docetaxel
干预措施: vandetanib (Drug)
Arm 1
vandetanib and docetaxel
干预措施: proteomic profiling (Genetic)
Arm 1
vandetanib and docetaxel
干预措施: laboratory biomarker analysis (Other)
Arm 1
vandetanib and docetaxel
干预措施: pharmacological study (Other)
结局指标
主要结局
Pharmacodynamic parameters (percent inhibition of pERK, pKDR, and pEGFR)
时间窗: 6 months
次要结局
- Association between scientific correlates (microvessel density, cell death, circulating endothelial cells, ERK and pERK, and serum proteomics) and treatment outcomes and other patient characteristics(6 months)
- Correlation of pharmacokinetic profile with pharmacodynamic data and treatment-related toxicities(6 months)
- Objective tumor response and clinically stable disease in patients with measurable disease at baseline(6 months)