A Multicenter Prospective Phase III Clinical Trial of Neoadjuvant CapOx Chemotherapy in Patients With Intermediate Risk Middle and Upper Rectal Cancer
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 560
- 试验地点
- 1
- 主要终点
- 3-year disease-free survival
研究概览
简要总结
The purpose of this study is to determine whether 4 cycles of neoadjuvant CapOx chemotherapy is more effective than the upfront surgery in patients with intermediate risk CRM"-" mid and upper rectal cancer.
详细描述
This trial aims to investigate the efficacy of neoadjuvant chemotherapy compared to upfront surgery in intermediate risk rectal cancer patients. This is a prospective multicenter open-label randomized phase III clinical trial. Patients will be randomized using an online randomization system to receive either 4 cycles of neoadjuvant CapOx (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 per os bid days 1-14) chemotherapy and surgery or surgery alone. A stratification will be performed based on N stage, tumor location in the middle or upper rectum and clinical center. Patients with cT3-4aN1-2M0, T4aN0M0 cancer in the upper rectum and сТ2-Т3bN1M0 (based on preoperative MRI) cancer in the middle rectum are included. All patients are potential candidates for adjuvant chemotherapy, according to preoperative staging. Chemoradiotherapy (50 Gy with concomitant capecitabine 825 mg/m2 per os bid on radiation days) will be performed for patients with tumor progression after neoadjuvant chemotherapy. The decision to proceed with adjuvant chemotherapy postoperatively will be based on pTNM stage in both treatment arms, according to actual treatment guidelines. The target accrual is 280 patients in each treatment arm (including 10% potential data loss) based on potential benefit of 10% 3-yr disease-free survival (75% vs 85%), α=0,05, power 80% in the experimental arm. An interim analysis is planned after 50% of the patients will reach a 3-year followup. Pelvic Magnetic Resonance Imaging (MRI) is performed in all patients for staging before and after neoadjuvant chemotherapy and before surgery. Pelvic MRI isbject to central review. Conduction of this study and data collection are controlled by a local institutional board.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent
- •Histologically verified colon rectal adenocarcinoma
- •cT3-4aN1-2M0 cancer of the upper rectum or сТ2-Т3bN1M0 cancer of the middle rectum (based on pelvic MRI)
- •Tumor more than 2 mm from mesorectal fascia (based on pelvic MRI)
- •Eastern Cooperative Oncology Group (ECOG) status 0-2
- •Haemoglobin (HGB) > 90 g/L
- •Platelet Count (PLT) > 120x10*9/L
- •Serum creatinine < 150 µmol/L
- •Total bilirubin < 25 µmol/L
排除标准
- •inability to obtain informed consent
- •distant metastases
- •synchronous or metachronous tumors
- •previous chemotherapy or radiotherapy
- •clinically significant cardiovascular disorders (myocardial infarction < 6 months before visit, stroke < < 6 months before visit, instable angina < 3 months before visit, arrhythmia, uncontrolled hypertension > 160/100 mm hg
- •clinically significant neurological disorders
- •previous neuropathy 2 or higher
- •current infection or heavy systemic disease
- •pregnancy, breastfeeding
- •ulcerative colitis
- •individual intolerance to treatment components
- •proven dihydropyrimidine dehydrogenase (DPD) deficiency
- •participation in other clinical trials
- •psychiatric disorders, which render patient unable to follow instructions or understand his/her condition
- •technical inability to perform pelvic MRI
- •inability of long-term followup of the patient
研究组 & 干预措施
4xCapOx
Patients will receive 4 cycles of neoadjuvant CapOx chemotherapy (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 bid per os days 1-14 every 3 weeks). In case of partial response or stable disease (based on pelvic MRI) patients proceed to surgery. In case of disease progression patients receive 50 Gy pelvic chemoradiotherapy with capecitabine 825 mg/m2 bid per os on radiation days and then surgery. The decision to proceed with adjuvant chemotherapy postoperatively will be based on pTNM stage
干预措施: Capecitabine (Drug)
4xCapOx
Patients will receive 4 cycles of neoadjuvant CapOx chemotherapy (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 bid per os days 1-14 every 3 weeks). In case of partial response or stable disease (based on pelvic MRI) patients proceed to surgery. In case of disease progression patients receive 50 Gy pelvic chemoradiotherapy with capecitabine 825 mg/m2 bid per os on radiation days and then surgery. The decision to proceed with adjuvant chemotherapy postoperatively will be based on pTNM stage
干预措施: Oxaliplatin (Drug)
4xCapOx
Patients will receive 4 cycles of neoadjuvant CapOx chemotherapy (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 bid per os days 1-14 every 3 weeks). In case of partial response or stable disease (based on pelvic MRI) patients proceed to surgery. In case of disease progression patients receive 50 Gy pelvic chemoradiotherapy with capecitabine 825 mg/m2 bid per os on radiation days and then surgery. The decision to proceed with adjuvant chemotherapy postoperatively will be based on pTNM stage
干预措施: Radiotherapy (Radiation)
4xCapOx
Patients will receive 4 cycles of neoadjuvant CapOx chemotherapy (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 bid per os days 1-14 every 3 weeks). In case of partial response or stable disease (based on pelvic MRI) patients proceed to surgery. In case of disease progression patients receive 50 Gy pelvic chemoradiotherapy with capecitabine 825 mg/m2 bid per os on radiation days and then surgery. The decision to proceed with adjuvant chemotherapy postoperatively will be based on pTNM stage
干预措施: Rectal cancer surgery (Procedure)
Surgery
Patients will receive standard surgery for rectal cancer with partial or total mesorectal excision (based on exact tumor location and surgeons discretion). The decision to proceed with adjuvant chemotherapy postoperatively will be based on pTNM stage
干预措施: Capecitabine (Drug)
Surgery
Patients will receive standard surgery for rectal cancer with partial or total mesorectal excision (based on exact tumor location and surgeons discretion). The decision to proceed with adjuvant chemotherapy postoperatively will be based on pTNM stage
干预措施: Oxaliplatin (Drug)
Surgery
Patients will receive standard surgery for rectal cancer with partial or total mesorectal excision (based on exact tumor location and surgeons discretion). The decision to proceed with adjuvant chemotherapy postoperatively will be based on pTNM stage
干预措施: Rectal cancer surgery (Procedure)
结局指标
主要结局
3-year disease-free survival
时间窗: 3 years
次要结局
- local recurrence rate(3 years)
- 3-year overall survival(3 years)
- Adjuvant chemotherapy compliance(6 months)
- Acute chemotherapy toxicity(14 weeks)
- pathologic complete response rate (pCR)(1 month)
- Operative morbidity(30 days)
- Neoadjuvant chemotherapy disease progression rate(14 weeks)
- Preoperative tumor-associated complications rate(14 weeks)
研究者
Sergey Gordeyev
Principal Investigator, Consultant surgeon
Blokhin's Russian Cancer Research Center