A Prospectively Randomized Phase III Trial Comparing Short-term mFOLFOXIRI, Long-term mFOLFOX6 and Traditional Chemoradiation as Preoperative Neoadjuvant Therapy for Locally Advanced Rectal Cancer
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 933
- 主要终点
- Disease-free survival
研究概览
简要总结
Preoperative radiation with single agent chemotherapy as sensitizer is the standard care of locally advanced rectal cancer.
Local irradiation significantly increases surgical complications and impairs quality of life.
Combination chemotherapy alone seems promising and provides similar benefit to chemoradiation as neoadjuvant therapy.
Early administration of systemic therapy is also proved beneficial for long-term survival.
The purpose of this study is to compare the efficacy of chemotherapy alone with short-term modified FOLFOXIRI or long-term mFOLFOX with standard chemoradiation as neoadjuvant therapy for locally advanced rectal cancer.
详细描述
Patients with cT3-4 or cN+ and cM0 by pelvic MR and chest + abdominal CT scan will be randomized to the following three groups:
Group A: Traditional chemoradiation.
Fluorouracil 225 mg/m2/day continuous intravenous infusion on weekdays for five weeks; local irradiation 2GY/day on weekdays, totally 50GY.
At the end of chemoradiation, patients will receive an evaluation with MR and CT scan.
If the efficacy is defined as CR, PR or SD, the TME will be performed in 6-8 weeks since the last irradiation.
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
- •1）Age: 18 to 75 years old;
- •2）Histological diagnosis of rectal adenocarcinoma;
- •3）Distance form anal margin ≤ 12cm: cT3-4 or cN+ and cM0 by pelvic MR and chest + abdominal CT, estimated possible for R0 resection;
- •4）There is no signs of intestinal obstruction, or obstruction of intestinal after treating with proximal colostomy has been relieved;
- •5）Patients did not previously receive rectal surgery, chemotherapy or radiation therapy , biological treatment , except for endocrine therapy;
- •6）ECOG Performance Status :0-1
- •7）Life expectancy: more than 3 years;
- •8）sufficient bone marrow, liver and kidney function.
排除标准
- •1）Arrhythmia requires treatment with antiarrhythmia (except for beta-blockers or digoxin), symptomatic coronary artery disease, myocardial ischemia (myocardial infarction within the last 6 months) or congestive heart failure exceeding NYHA class II;
- •2）Severe hypertension with poor control;
- •3）History of HIV infection or active phase of chronic hepatitis B or C infection with high copy viral DNA;
- •4）Other active serious infections according to NCI-CTC version 4.0;
- •5）There is preoperative evidence for distant metastasis outside pelvis;
- •6）Cachexia and organ function decompensation
- •7）History of pelvic or abdominal radiotherapy;
- •8）Multiple primary cancer;
- •9）Patients with epilepcy requiring treatment ( steroids or antiepileptic treatment);
- •10）History of other malignant tumors within 5 years, except for cured cervical carcinoma in situ or skin basal cell carcinoma;
- •11）Drug abuse and medical, psychological or social conditions interfering patient participation in research or the evaluation of research results;
- •12）Any allergy to clinical research drugs or any drugs associated with this study;
- •13）Any unstable condition or condition that may endanger safety and compliance of patients;
- •14）Pregnancy or the lactating female without adequate contraception.
研究组 & 干预措施
5-Fu + RT
5Fu + RT for five weeks --- 6-8 weeks of interval --- TME --- mFOLFOX * 6-8
干预措施: Chemoradiation (Radiation)
mFOLFOXIRI
mFOLFOXIRI * 4 --- TME --- mFOLFOXIRI * 4
干预措施: FOLFOXIRI Protocol (Drug)
mFOLFOX
mFOLFOX * 9 --- TME --- mFOLFOX * 3
干预措施: Folfox Protocol (Drug)
结局指标
主要结局
Disease-free survival
时间窗: 3 years
The interval from randomization to local recurrence, distant metastasis, death or the last follow-up.
次要结局
- Surgical complication(3 years)
- Recurrence-free survival(3 years)
- Metastasis-free survival(3 years)
- Treatment related quality of life(up to 3 years)