A Phase I Study of Rapamycin in Combination With Bevacizumab in Patients With Unresectable Hepatocellular Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 27
- 试验地点
- 2
- 主要终点
- Dose-limiting toxicity
研究概览
简要总结
RATIONALE: Sirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab and sirolimus may also stop the growth of liver cancer by blocking blood flow to the tumor. Giving sirolimus together with bevacizumab may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of sirolimus when given together with bevacizumab in treating patients with liver cancer that cannot be removed by surgery.
详细描述
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of sirolimus used in combination with bevacizumab in patients with unresectable hepatocellular carcinoma.
- Determine the toxicity profile of this regimen in these patients.
Secondary
- Determine the clinical activity of this regimen in these patients.
- Determine the pharmacokinetics of sirolimus in these patients.
- Determine the biologically active dose range of sirolimus in these patients.
- Correlate phosphorylated p70S6K activity with clinical response in patients treated with this regimen.
- Correlate PTEN, 4EBP-1, phosphorylated p70S6K, CD31, and vascular endothelial growth factor expression with clinical response in patients treated with this regimen.
- Correlate the degree of angiogenesis (as measured by DCE-CT scan) with drug levels and clinical response.
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
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Phase I study of rapamycin and bevacizumab
Rapamycin (available as 1mg per tablet; Wyeth) will be given orally once in the morning before meal. The starting dose of rapamycin will be 1mg administered once daily. All doses of rapamycin will be preceded by an oral loading dose three times the maintenance dose on day 1. The dose of rapamycin will be increased at each dose level.
Bevacizumab (100mg/4ml; Roche) will start concurrently with rapamycin. It will be diluted in a total of 100ml of 0.9% sodium chloride given via intravenous injection. The first dose will be infused over 90 minutes. If the first infusion is tolerated without any adverse infusion-related events (fever and/or chills), the second infusion may be delivered over 60 minutes. If the 60- minute infusion is well tolerated, the subsequent doses may be delivered over 30 minutes.
干预措施: Rapamycin (Drug)
Phase I study of rapamycin and bevacizumab
Rapamycin (available as 1mg per tablet; Wyeth) will be given orally once in the morning before meal. The starting dose of rapamycin will be 1mg administered once daily. All doses of rapamycin will be preceded by an oral loading dose three times the maintenance dose on day 1. The dose of rapamycin will be increased at each dose level.
Bevacizumab (100mg/4ml; Roche) will start concurrently with rapamycin. It will be diluted in a total of 100ml of 0.9% sodium chloride given via intravenous injection. The first dose will be infused over 90 minutes. If the first infusion is tolerated without any adverse infusion-related events (fever and/or chills), the second infusion may be delivered over 60 minutes. If the 60- minute infusion is well tolerated, the subsequent doses may be delivered over 30 minutes.
干预措施: Bevacizumab (Drug)
结局指标
主要结局
Dose-limiting toxicity
时间窗: 3 years
Maximum tolerated dose
时间窗: 3 years
次要结局
- Response rate (complete and partial response and stable disease)(3 years)
- Progression-free survival(3 years)
- Overall survival(3 years)
- Distribution of p70S6K activity in peripheral blood mononuclear cells(3 years)
- Correlation of p70S6K with tumor response(3 years)
- Expression of tumor tissue biomarkers (PTEN, 4EBP-1, CD31, p70S6K, and vascular endothelial growth factor)(3 years)
- Correlation of tumor biomarkers with response(3 years)
- Best overall response (complete and partial response; stable and progressive disease)(3 years)
- Change in DCE-CT scan assessment of angiogenesis(3 years)
研究者
Choo Su Pin
Senior Consultant
National Cancer Centre, Singapore