Effect of Concurrent Capecitabine-based Long-term Radiotherapy Followed by 4 Cycles XELOX Pre- a Delayed TME Compared With 6 Cycles XELOX post-a Regular Timing TME in Patients With High Risk Rectal Cancer: a Multi-centers, Randomized, Open-Label Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 244
- 试验地点
- 2
- 主要终点
- Pathological complete response rate
研究概览
简要总结
The purpose of this study was to evaluate the effect of concurrent capecitabine-based long-term radiotherapy followed by 4 cycles XELOX pre- a delayed TME compared with 6 cycles XELOX post- a Regular Timing TME in patients with high-risk rectal cancer defined by MRI.
详细描述
This is the randomized controlled, multi-centers, and open-labeled study. Delivering systemic chemotherapy between concurrent capecitabine-based long-term radiotherapy and total mesorectal excision (TME) surgery would be more effectively improved local control rates and improved metastases-free survival rates. The investigators attempted to investigate the effect on pathological response of delivering 4 cycles XELOX between concurrent capecitabine-based long-term radiotherapy and TME with lengthening the interval from radiation to surgery. In this study, the participants with high risk of deeper infiltration, or extramural vessel invasion, or circumferential resection margin involvement, or surrounding organs and structures invaded et al. were recruited. The participants will be randomized (1:1 ratio) to a control and intervention arm. The participants in the control arm will receive best current practice of concurrent capecitabine-based long-term radiotherapy followed by TME and then a 6 cycles of XELOX as standard adjuvant chemotherapy. The participants in the intervention arm will receive concurrent capecitabine-based long-term radiotherapy followed by 4 cycles XELOX as neoadjuvant chemotherapy pre- a delayed TME.
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
盲法说明
Open Label
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
- •Age of 18-75 years;
- •Histologically confirmed adenocarcinoma;
- •The rectal adenocarcinoma 0-12cm from the anal margin on Magnetic resonance imaging (MRI) and/or rigid sigmoidoscopy;
- •High risk of rectal cancer defined by high-resolution MRI: tumor invasion 5mm beyond the muscularis propria, or extramural vascular invasion, or circumferential resection margin unsafe, or the lower rectal cancer invades intersphincteric space, or rectal cancer invades the adjacent structures.
- •Eastern Collaborative Oncology Group performance status score of 0 or 2
- •Able and willing to give informed consent to participate.
排除标准
- •Received preoperative chemoradiotherapy for rectal cancer before the recruitment of this study;
- •Have metastatic disease (including non-regional lymph nodes metastases or resectable liver metastases);
- •Other malignancies, non-adenocarcinoma rectal malignancies or rectal malignancies on the basis of inflammatory bowel disease;
- •Emergency surgery due to bowel obstruction, perforation, bleeding, etc.;
- •Abnormality of capecitabine absorption due to gastrointestinal disease e.g. short bowel syndrome, inflammation bowel disease, et al.;
- •Unresectable concurrent intestinal lesions;
- •Concurrent severe infection；
- •Cardiac Disease：uncontrolled or symptomatic cardiac angina，or uncontrolled arrhythmias and hypertension, or severe congestive heart failure grade II or more based on New York Heart Association (NYHA); myocardial infarction within the past 12 months
- •Peripheral neuropathy more than grade 1 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE; version 3·0)
- •Bone marrow, liver and kidney function are abnormal e.g., white blood cell ≤ 1.5 × 109 / L; platelet ≤ 100 × 109 / L; Haemoglobin ≤ 80 g/L; Bilirubin > 1.5 times the upper limit; aspartate aminotransferase and alanine aminotransferase > 2.5 times the upper limit; creatinine > 1.5 times the upper limit;
- •Pregnant or lactating women;
- •Life prediction less than 3 months, other severe diseases;
- •Contraindication to MRI; e.g. non-MRI compatible hip prosthesis, cardiac pacemaker;
- •Contraindication to standard chemotherapy including drug interactions and glomerular filtration rate <50 mL/min at baseline;
- •Participators who had been recruited by other clinical trial within three months.
研究组 & 干预措施
4 Cycles XELOX pre- TME
experimental group (arm B): concurrent capecitabine-based long-term radiotherapy, 4 cycles of XELOX as neoadjuvant chemotherapy and TME surgery
干预措施: concurrent capecitabine-based long-term radiotherapy followed by 4 cycles XELOX and a delayed TME (Drug)
6 Cycles XELOX post- TME
control group (arm A): concurrent capecitabine-based long-term radiotherapy, TME surgery and 6 cycles of XELOX as adjuvant chemotherapy.
干预措施: concurrent capecitabine-based long-term radiotherapy followed by a Regular TME and 6 Cycles XELOX (Drug)
结局指标
主要结局
Pathological complete response rate
时间窗: up to 30days after total mesorectal excision
Pathological complete response (pCR) rate between control and intervention arm
次要结局
- Disease Free Survival(3-year)
- Surgery morbidity(30 days and 12-months)
- quality of surgery(Time of surgery)
- R0 of total mesorectal excision rate(up to 30days after total mesorectal excision)
研究者
YE Yingjiang
Department of GI Surgery
Peking University People's Hospital