A Phase II, Multicentre, Open-Label, Randomised Study of Neoadjuvant Chemotherapy and Bevacizumab in Patients With MRI Defined High-Risk Cancer of the Rectum
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 11
- 主要终点
- Pathological Complete Response (PCR)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy, toxicity and feasibility of FOLFOX/ bevacizumab and FOLFOXIRI/ bevacizumab neoadjuvant therapy in poor prognosis rectal cancer as defined by MRI.
详细描述
The purpose of this study is to look at two different combinations of anticancer drugs to see how effective they are at shrinking your cancer and preventing it from coming back after surgery. Patients with locally advanced rectal cancer are sometimes treated with radiotherapy, with or without chemotherapy, before having surgery. Radiotherapy treats only the main tumour in the rectum. This means that if tiny deposits of cancer have spread to other parts of the body (metastases), these could continue to grow. Giving chemotherapy and radiotherapy together (chemoradiotherapy) can treat both the main tumour and any spread. However, due to the side-effects we can't give as much chemotherapy in combination with radiotherapy than if chemotherapy were given on its own and treatment of possible metastases may not be as good as it could be. If the risk of the main tumour coming back is quite small, then giving treatment that targets metastases should be the best option.
This study looks at two well known combinations of chemotherapy drugs: FOLFOX (folinic acid, 5-fluorouracil, oxaliplatin) and FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, irinotecan). Chemotherapy works by killing cancer cells. In addition, the anticancer drug bevacizumab will be given with both the FOLFOX and FOLFOXIRI. Bevacizumab is an "anti-angiogenesis" drug. It works by stopping tumours from making new blood vessels. Without new blood vessels, the cancer cells do not get the food and oxygen they need to survive and grow. Attacking the cancer in these ways may be more effective than chemotherapy alone.
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 75 Years（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
FOLFOX & Bevacizumab
Bevacizumab - 5 mg/kg IV over 30-90 minutes (cycles 1-5 only), Oxaliplatin - 85 mg/m2 IV over 2 hours, Folinic acid - 350 mg IV over 2 hours, 5-Fluorouracil - 3200 mg/m2 IV continuous infusion over 48 hour.
Treatment given every 2 weeks for 12 weeks (for 6 cycles)
干预措施: Bevacizumab (Biological)
FOLFOX & Bevacizumab
Bevacizumab - 5 mg/kg IV over 30-90 minutes (cycles 1-5 only), Oxaliplatin - 85 mg/m2 IV over 2 hours, Folinic acid - 350 mg IV over 2 hours, 5-Fluorouracil - 3200 mg/m2 IV continuous infusion over 48 hour.
Treatment given every 2 weeks for 12 weeks (for 6 cycles)
干预措施: Oxaliplatin (Drug)
FOLFOX & Bevacizumab
Bevacizumab - 5 mg/kg IV over 30-90 minutes (cycles 1-5 only), Oxaliplatin - 85 mg/m2 IV over 2 hours, Folinic acid - 350 mg IV over 2 hours, 5-Fluorouracil - 3200 mg/m2 IV continuous infusion over 48 hour.
Treatment given every 2 weeks for 12 weeks (for 6 cycles)
干预措施: 5-Fluorouracil (Drug)
FOLFOXIRI & Bevacizumab
Bevacizumab - 5 mg/kg IV over 30-90 minutes (cycles 1-5 only), Irinotecan - 165 mg/m2 IV over 1 hour, Oxaliplatin - 85 mg/m2 IV over 2 hours, Folinic acid - 350 mg IV over 2 hours, 5-Fluorouracil - 3200 mg/m2 IV continuous infusion over 48 hour.
Treatment given every 2 weeks for 12 weeks (for 6 cycles)
干预措施: Bevacizumab (Biological)
FOLFOXIRI & Bevacizumab
Bevacizumab - 5 mg/kg IV over 30-90 minutes (cycles 1-5 only), Irinotecan - 165 mg/m2 IV over 1 hour, Oxaliplatin - 85 mg/m2 IV over 2 hours, Folinic acid - 350 mg IV over 2 hours, 5-Fluorouracil - 3200 mg/m2 IV continuous infusion over 48 hour.
Treatment given every 2 weeks for 12 weeks (for 6 cycles)
干预措施: Irinotecan (Drug)
FOLFOXIRI & Bevacizumab
Bevacizumab - 5 mg/kg IV over 30-90 minutes (cycles 1-5 only), Irinotecan - 165 mg/m2 IV over 1 hour, Oxaliplatin - 85 mg/m2 IV over 2 hours, Folinic acid - 350 mg IV over 2 hours, 5-Fluorouracil - 3200 mg/m2 IV continuous infusion over 48 hour.
Treatment given every 2 weeks for 12 weeks (for 6 cycles)
干预措施: Oxaliplatin (Drug)
FOLFOXIRI & Bevacizumab
Bevacizumab - 5 mg/kg IV over 30-90 minutes (cycles 1-5 only), Irinotecan - 165 mg/m2 IV over 1 hour, Oxaliplatin - 85 mg/m2 IV over 2 hours, Folinic acid - 350 mg IV over 2 hours, 5-Fluorouracil - 3200 mg/m2 IV continuous infusion over 48 hour.
Treatment given every 2 weeks for 12 weeks (for 6 cycles)
干预措施: 5-Fluorouracil (Drug)
结局指标
主要结局
Pathological Complete Response (PCR)
时间窗: The pCR rate will be assessed after surgery, therefore approximately 24 weeks after randomisation.
The proportion of patients in each arm who achieve a pCR will be presented, along with a 95% CI. Within each group the achieved pCR rate will be compared to the rate achieved by radiotherapy alone (5%).
次要结局
- T and N stage downstaging(This will be assessed at the completion of treatment. Treatment will be given for up to 12 weeks.)
- Overall Survival(From study entry until death, until 3 years after randomisation.)
- 1 year Colostomy Rate(Post surgery (approximately 24 weeks after randomisation) and 1 year after randomisation.)
- Frequency and severity of Adverse Events(This will be from date of randomisation until 30 days after completion of treatment. Treatment is given for up to 12 weeks.)
- Local Control(From date of surgery until local failure, until 3 years after randomisation.)
- Tumour Regression Grade (TRG)(Assessed after surgery, approximately 24 weeks after randomisation.)
- RECIST Response Rate(This will be assessed after chemotherapy has ended. Chemotherapy will be given for up to 12 weeks.)
- Compliance of Chemotherapy(This will be at the end of treatment (up to 12 weeks))
- CRM Negative Resection Rate(This will be assessed after surgery, therefore approximately 24 weeks after randomisation.)
- Progression Free Survival(This will be assessed pre-cycle 4 and post-treatment, therefore at 6 weeks and 12 weeks after randomisation.)
- Disease Free Survival(This will be length of time from date of surgery till relapse, second colorectal primary or death from any cause, whichever occurs first. These occurrences will be reported on CRFs every six months for up to three years.)
- Tumour Cell Density(This will be assessed after surgery, approximately 24 weeks after randomisation.)