Tocotrienol and Bevacizumab in Metastatic Colorectal Cancer. A Randomized Phase II Marker Trial
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 83
- 试验地点
- 2
- 主要终点
- The rate of progression free patients at six months
研究概览
简要总结
This double blind, randomized phase II trial will investigate whether the addition of tocotrienol will improve the effect and lower the toxicity of standard chemotherapy and bevacizumab. Half of the patients will receive tocotrienol and the other half placebo. Treatment is planned for a period of maximum six months and will be discontinued earlier in case of progression or unacceptable toxicity.
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
- Triple (Participant, Care Provider, Investigator)
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
- •Histopathologically verified adenocarcinoma of the colon or rectum
- •Metastatic disease
- •Planned treatment with FOLFOX or capecitabine combined with bevacizumab
- •Evaluable disease according to RECIST 1.1
- •Performance status 0-2
- •Expected survival ≥ 3 months
- •Patient acceptance to collection of blood samples for translational research
- •Age ≥ 18 years
- •Contraception during and 6 months after last dose for women of childbearing potential (less than one year amenorrhea and not undergone hysterectomy, bilateral salpingectomy or bilateral oophorectomy) and for male patients with a fertile partner. Hormonal contraception, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner, or sexual abstinence is accepted.
- •Adequate bone marrow function, liver function, and renal function (within 7 days prior to inclusion):
- •WBC ≥ 3.0 x 109/l or neutrophils (ANC) ≥ 1.5 x 10^9/l
- •Platelet count ≥ 100 x 10^9/l
- •Hemoglobin ≥ 6.0 mmol/l
- •Serum bilirubin ≤ 2.0 x ULN
- •Serum transaminase ≤ 2.5 x ULN
- •Serum creatinine ≤ 1.5 ULN
- •Urine dipstick for protein ≤ 2+, if the dipstick shows protein ≥ 2+, 24 hour urine testing must be performed and show protein contents ≤ 1g.
- •Written and orally informed consent
排除标准
- •Other active malignant disease within 5 years prior to inclusion in the study.
- •Other experimental therapy within 28 days prior to treatment initiation.
- •Underlying medical disease not adequately treated.
- •Surgery, including open biopsy, within 4 weeks prior to first dose of bevacizumab.
- •Cerebral vascular attack, transient ischemic attack or subarachnoid hemorrhage within six months before start of treatment
- •Bleeding tumor
- •Pregnant or breastfeeding women
- •Fertile patients not willing to use effective methods of contraception during treatment and for six months after end of treatment.
- •Hypersensitivity to one or more active substances or auxiliary substances
研究组 & 干预措施
Arm A, standard treatment + tocotrienol
Fluorouracil + calcium folinate + oxaliplatin + bevacizumab + tocotrienol OR capecitabine + bevacizumab + tocotrienol
干预措施: Calcium folinate (Drug)
Arm B, standard treatment + placebo
Fluorouracil + calcium folinate + oxaliplatin + bevacizumab + placebo OR capecitabine + bevacizumab + placebo
干预措施: Placebo (Other)
Arm A, standard treatment + tocotrienol
Fluorouracil + calcium folinate + oxaliplatin + bevacizumab + tocotrienol OR capecitabine + bevacizumab + tocotrienol
干预措施: Tocotrienol (Dietary Supplement)
Arm A, standard treatment + tocotrienol
Fluorouracil + calcium folinate + oxaliplatin + bevacizumab + tocotrienol OR capecitabine + bevacizumab + tocotrienol
干预措施: Fluorouracil (Drug)
Arm A, standard treatment + tocotrienol
Fluorouracil + calcium folinate + oxaliplatin + bevacizumab + tocotrienol OR capecitabine + bevacizumab + tocotrienol
干预措施: Oxaliplatin (Drug)
Arm B, standard treatment + placebo
Fluorouracil + calcium folinate + oxaliplatin + bevacizumab + placebo OR capecitabine + bevacizumab + placebo
干预措施: Calcium folinate (Drug)
Arm A, standard treatment + tocotrienol
Fluorouracil + calcium folinate + oxaliplatin + bevacizumab + tocotrienol OR capecitabine + bevacizumab + tocotrienol
干预措施: Bevacizumab (Drug)
Arm A, standard treatment + tocotrienol
Fluorouracil + calcium folinate + oxaliplatin + bevacizumab + tocotrienol OR capecitabine + bevacizumab + tocotrienol
干预措施: Capecitabine (Drug)
Arm B, standard treatment + placebo
Fluorouracil + calcium folinate + oxaliplatin + bevacizumab + placebo OR capecitabine + bevacizumab + placebo
干预措施: Fluorouracil (Drug)
Arm B, standard treatment + placebo
Fluorouracil + calcium folinate + oxaliplatin + bevacizumab + placebo OR capecitabine + bevacizumab + placebo
干预措施: Bevacizumab (Drug)
Arm B, standard treatment + placebo
Fluorouracil + calcium folinate + oxaliplatin + bevacizumab + placebo OR capecitabine + bevacizumab + placebo
干预措施: Oxaliplatin (Drug)
Arm B, standard treatment + placebo
Fluorouracil + calcium folinate + oxaliplatin + bevacizumab + placebo OR capecitabine + bevacizumab + placebo
干预措施: Capecitabine (Drug)
结局指标
主要结局
The rate of progression free patients at six months
时间窗: Six months after enrollment of the last patient
次要结局
- Time to first serious adverse event according to CTCAE 5.0(Six months after enrollment of the last patient)
- Overall survival(12 months after enrollment of the last patient)
- Response rate as measured by RECIST 1.1(Six months after enrollment of the last patient)