A Clinical Trial Testing Rapamycin, an mTOR-inhibitor, in Combination With Preoperative Radiotherapy in Operable Rectum Cancer: a Phase I and Phase II Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Phase I: Incidence of severe postoperative complications (grade IV or grade V),
研究概览
简要总结
Investigating the safety and the activity of Rapamycin, administered before and during preoperative radiotherapy in patients with an operable colorectal carcinoma. The phase I dose escalation study will be performed in three steps (2, 4 and 6 mg). Patients entered in phase II will follow the same tolerable treatment regimen as patients in phase I study.
详细描述
Treatment regimen Phase I A daily dose of Rapamycin will be taken during 13 days. At step 1 a dose of 2 mg will be given once a day; at step 2 a dose of 4 mg will be given once a day; at step 3 a dose of 6 mg will be given once a day.
Preoperative radiotherapy (5x 5 Gy) will be administered at day 8-12, followed by TME-surgery at day 15.
Phase II A daily dose of 6 mg Rapamycin will be taken for 14 days (unless the optimal dose found in the phase I study is lower).
Preoperative radiotherapy (5x 5 Gy) will be administered at day 9-15, followed by TME-surgery 7-8 weeks post RT.
Sample size Phase I dose-escalation study Minimum 3 eligible patients per step, maximum 6 eligible patients per step. Phase II A total of 47 patients will be entered in this part of the study.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically proven rectum cancer
- •UICC TNM I-III
- •WHO performance status 0-2
- •Less than 10% weight loss the last 6 months
- •No recent (< 3 months) severe cardiac disease
- •Normal serum bilirubin and serum creatinin
排除标准
- •Concurrent chemotherapy with radiation
- •History of prior pelvis radiotherapy
- •Recent (<3 months) myocardial infarction
- •Uncontrolled infectious disease
- •Concurrent medication known as inhibitors of CYP3A4 susceptible to increase Rapamycin blood concentrations
研究组 & 干预措施
Rapamycine
rapamycine 6 mg dd
干预措施: Rapamycin (Drug)
结局指标
主要结局
Phase I: Incidence of severe postoperative complications (grade IV or grade V),
时间窗: within the first 6 weeks after surgery
assessed according to CTCv3.0
时间窗: within the first 6 weeks after surgery
Phase II: Tumour blood flow assessed CT-PET + CTp
时间窗: day 64
次要结局
- Phase I:Incidence of other acute toxicity, assessed according to CTCv 3.0(within the first 6 weeks after surgery)
- Activation status of mTor related and dependent molecules in the tumour(within the first 6 weeks after surgery)
- Phase II:Maximum standardised Uptake Value (SUV) of 18F-FDG, assessed bij PET-CT-scan(day 64)
- Phase II:Incidence of acute side effects of rapamycin, assessed according to CTCv 4.0(day 8, 15, 22, 36, 50 and 64)