A Multicenter Prospective Phase III Clinical Trial of Neoadjuvant CapOx in Patients With Intermediate Risk CRM-negative Middle Rectal Cancer
试验速览
- 阶段
- 3 期
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 316
- 试验地点
- 1
- 主要终点
- 2-year local recurrence rate
研究概览
简要总结
The purpose of this study is to determine whether 3 months of neoadjuvant CapOx is non-inferior to neoadjuvant radiotherapy in patients with moderate risk CRM"-" mid rectal cancer.
详细描述
This trial aims to investigate the efficacy of neoadjuvant chemotherapy compared to 5x5 Gy neoadjuvant radiotherapy in moderate risk CRM-negative rectal cancer patients. This is a prospective multicenter open-label non-inferiority 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, surgery and 4 cycles of adjuvant CapOx chemotherapy or 5x5 Gy radiotherapy, surgery and 8 cycles of adjuvant CapOx chemotherapy. A stratification will be performed based on сN stage and clinical center. Patients with сT3c-T3dN0-1M0, cT1-T3dN2M0 cancer in the middle rectum are included. 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 main hypothesis is that the 2-year local recurrence rate is non-inferior after neoadjuvant chemotherapy and neoadjuvant radiotherapy in moderate risk mid rectal cancer patients. The target accrual is 158 patients in each treatment arm (including 10% potential data loss) based on non-recurrence rate of 98% in investigated and 96% in the control group with a non-inferiority margin of 3%, α=0,05, power 80%. An interim analysis is planned after 50% of the patients will reach a 2-year followup. Pelvic Magnetic Resonance Imaging (MRI) is performed in all patients for staging before and after neoadjuvant chemotherapy and before surgery. Pelvic MRI is subject 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 75 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
- •сT3c-T3dN0-1M0, cT1-T3dN2M
- •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
Neoadjuvant chemotherapy
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 within 2 weeks. 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 following 8-10 weeks. After surgery patients receive 4 cycles of adjuvant CapOx chemotherapy (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 bid per os days 1-14 every 3 weeks).
干预措施: Capecitabine (Drug)
Neoadjuvant chemotherapy
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 within 2 weeks. 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 following 8-10 weeks. After surgery patients receive 4 cycles of adjuvant CapOx chemotherapy (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 bid per os days 1-14 every 3 weeks).
干预措施: Oxaliplatin (Drug)
Neoadjuvant chemotherapy
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 within 2 weeks. 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 following 8-10 weeks. After surgery patients receive 4 cycles of adjuvant CapOx chemotherapy (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 bid per os days 1-14 every 3 weeks).
干预措施: Radiotherapy (Radiation)
Neoadjuvant chemotherapy
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 within 2 weeks. 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 following 8-10 weeks. After surgery patients receive 4 cycles of adjuvant CapOx chemotherapy (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 bid per os days 1-14 every 3 weeks).
干预措施: Rectal cancer surgery (Procedure)
Neoadjuvant radiotherapy
Patients will receive 5x5 Gy radiotherapy and then surgery following 6-8 weeks. After surgery patients receive 8 cycles of adjuvant CapOx chemotherapy (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 bid per os days 1-14 every 3 weeks).
干预措施: Capecitabine (Drug)
Neoadjuvant radiotherapy
Patients will receive 5x5 Gy radiotherapy and then surgery following 6-8 weeks. After surgery patients receive 8 cycles of adjuvant CapOx chemotherapy (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 bid per os days 1-14 every 3 weeks).
干预措施: Oxaliplatin (Drug)
Neoadjuvant radiotherapy
Patients will receive 5x5 Gy radiotherapy and then surgery following 6-8 weeks. After surgery patients receive 8 cycles of adjuvant CapOx chemotherapy (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 bid per os days 1-14 every 3 weeks).
干预措施: Rectal cancer surgery (Procedure)
Neoadjuvant radiotherapy
Patients will receive 5x5 Gy radiotherapy and then surgery following 6-8 weeks. After surgery patients receive 8 cycles of adjuvant CapOx chemotherapy (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 bid per os days 1-14 every 3 weeks).
干预措施: Radiotherapy (Radiation)
结局指标
主要结局
2-year local recurrence rate
时间窗: 2 years
次要结局
- Adjuvant chemotherapy compliance(6 months)
- Acute chemotherapy toxicity(6 months)
- pathologic complete response rate (pCR)(1 month)
- 2-year overall survival(2 years)
- 2-year disease-free survival(2 years)
- Operative morbidity(30 days)
- Neoadjuvant chemotherapy disease progression rate(3 months)
- Preoperative tumor-associated complications rate(3 months)
研究者
Sergey Gordeyev
Principal Investigator, Consultant surgeon
Blokhin's Russian Cancer Research Center