Phase I Study of PS-341 in Combination With 5-Fluorouracil and External Beam Radiotherapy For The Treatment Of Locally Advanced And Metastatic Rectal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 11
- 试验地点
- 4
- 主要终点
- Maximum tolerated dose
研究概览
简要总结
RATIONALE: Bortezomib 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 fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving bortezomib and fluorouracil together with radiation therapy may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when given together with fluorouracil and external-beam radiation therapy in treating patients with stage II, stage III, or stage IV rectal cancer.
详细描述
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of bortezomib when administered in combination with fluorouracil and external beam radiotherapy as preoperative or palliative treatment in patients with stage II-IV rectal adenocarcinoma.
- Determine the dose-limiting toxicities of this regimen in these patients.
Secondary
- Determine the dose-effect relationship of bortezomib on NF-kappa B activation induced by chemoradiotherapy.
- Determine downstream events induced by NF-kappa B activation.
- Determine downstream events related to activation of p53 in response to treatment with chemoradiotherapy and bortezomib.
- Determine the rate of complete pathologic remission in patients who undergo surgical resection of their primary tumor.
- Determine the gene expression pattern of tumors by cDNA microarray analysis before and during treatment with this regimen.
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
Maximum tolerated dose
时间窗: 6 weeks
Dose-limiting toxicity
时间窗: 8 weeks
次要结局
- Dose-effect relationship of bortezomib on NF-kappa B activation induced by chemoradiotherapy(6 weeks)
- Downstream events induced by NF-kappa B activation(8 weeks)
- Downstream events related to activation of p53 in response to treatment with chemoradiotherapy and bortezomib(8 weeks)
- Rate of complete pathologic remission(2 years)
- Gene expression pattern of tumors as assessed by cDNA microarray analysis pre- and post-treatment(8 weeks)