Phase I/II Study of the Combination of Oxaliplatin / Docetaxel and ZACTIMA for the Treatment of Advanced Cancers of the Esophagus and Gastroesophageal Junction
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose of vandetanib when administered with oxaliplatin and docetaxel (Phase I)
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 oxaliplatin and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether vandetanib is more effective than a placebo when given together with oxaliplatin and docetaxel in treating advanced cancer of the esophagus or gastroesophageal junction.
PURPOSE: This randomized phase I/II trial is studying the side effects and best dose of vandetanib when given together with oxaliplatin and docetaxel and to see how well it works in treating patients with advanced cancer of the esophagus or gastroesophageal junction.
详细描述
OBJECTIVES:
Primary
- To determine the maximum tolerated dose of vandetanib when administered with oxaliplatin and docetaxel in patients with advanced cancer of the esophagus or gastroesophageal junction. (Phase I)
- To evaluate the toxicity of this regimen in these patients. (Phase I)
- To determine the progression-free survival of these patients. (Phase II)
Secondary
- To determine the response rate in patients treated with oxaliplatin and docetaxel with or without vandetanib. (Phase II)
- To determine the overall survival of patients treated with these regimens. (Phase II)
- To determine the toxicity of these regimens in these patients. (Phase II)
- To determine whether tumor characteristics (e.g., EGFR/ErbB2 expression, activation and mutational status of the EGFR and ErbB2 pathway [total and phosphorylated EGFR and ErbB2, mutational and FISH analysis] and tumoral expression of HIF1-alpha) may have an association with response and outcome. (Phase II)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
研究组 & 干预措施
Phase II arm I
Patients receive docetaxel IV over 1 hour on days 1 and 8, oxaliplatin IV over 2 hours on day 1, and oral vandetanib (at the maximum tolerated dose determined in phase I) once daily on days 1-21. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients with responding or stable disease may continue to receive vandetanib beyond 8 courses in the absence of disease progression or unacceptable toxicity.
干预措施: docetaxel (Drug)
Phase II arm I
Patients receive docetaxel IV over 1 hour on days 1 and 8, oxaliplatin IV over 2 hours on day 1, and oral vandetanib (at the maximum tolerated dose determined in phase I) once daily on days 1-21. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients with responding or stable disease may continue to receive vandetanib beyond 8 courses in the absence of disease progression or unacceptable toxicity.
干预措施: oxaliplatin (Drug)
Phase II arm I
Patients receive docetaxel IV over 1 hour on days 1 and 8, oxaliplatin IV over 2 hours on day 1, and oral vandetanib (at the maximum tolerated dose determined in phase I) once daily on days 1-21. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients with responding or stable disease may continue to receive vandetanib beyond 8 courses in the absence of disease progression or unacceptable toxicity.
干预措施: vandetanib (Drug)
Phase II arm II
Patients receive docetaxel and oxaliplatin as in arm I. Patients also receive an oral placebo once daily on days 1-21. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients with responding or stable disease may continue to receive vandetanib beyond 8 courses in the absence of disease progression or unacceptable toxicity.
干预措施: docetaxel (Drug)
Phase II arm II
Patients receive docetaxel and oxaliplatin as in arm I. Patients also receive an oral placebo once daily on days 1-21. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients with responding or stable disease may continue to receive vandetanib beyond 8 courses in the absence of disease progression or unacceptable toxicity.
干预措施: oxaliplatin (Drug)
Phase II arm II
Patients receive docetaxel and oxaliplatin as in arm I. Patients also receive an oral placebo once daily on days 1-21. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients with responding or stable disease may continue to receive vandetanib beyond 8 courses in the absence of disease progression or unacceptable toxicity.
干预措施: placebo (Other)
结局指标
主要结局
Maximum tolerated dose of vandetanib when administered with oxaliplatin and docetaxel (Phase I)
时间窗: Each cycle of treatment consists of 21 days. Dose-limiting toxicities will be defined during cycle 1 of therapy. Patients will need to be observed for at least 2 cycles. A maximum of eight cycles of chemotherapy will be allowed.
Progression-free survival (Phase II) at 5 months
时间窗: at 5 months
次要结局
- Response rate (Phase II)(Tumor assessment will be performed after even treatment cycles every 6 weeks.)
- Overall survival (Phase II)(follow for life)
- Toxicity of oxaliplatin and docetaxel in combination with vandetanib or placebo (Phase II)(Day 8 and 15 of each treatment cycle and follow up (every 8 weeks) after chemotherapy.)
- Correlation of tumor characteristics and tumoral expression with response and outcome (Phase II)(Tumor assessment will be performed after even treatment cycles every 6 weeks.)