Induction and Consolidation Chemotherapy in Locally Advanced Rectal Cancer Patients With Circumferential Resection Margin Involvement: a Multicenter Prospective Randomized Phase III Clinical Trial
试验速览
- 阶段
- 3 期
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 540
- 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 the addition of 2 cycles of induction CapOx chemotherapy and 2 cycles of consolidation CapOx chemotherapy to standard chemoradiation improves 3-year disease-free survival in patients with locally advanced CRM"+" mid and low rectal cancer.
详细描述
This trial aims to investigate the efficacy of adding neoadjuvant induction and consolidation chemotherapy compared to standard chemoradiotherapy in locally advanced rectal cancer patients with circumferential resection margin involvement. This is a prospective multicenter open-label randomized phase III clinical trial. Patients will be randomized using an online randomization system to receive either 2 cycles of induction CapOx (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 per os bid days 1-14) chemotherapy, followed by chemoradiotherapy (54 Gy in 2 Gy fractions with concomitant capecitabine 825 mg/m2 per os bid on radiation days), then 2 cycles of consolidation CapOx chemotherapy, surgery (10-12 weeks following chemoradiotherapy) and 2 cycles of adjuvant CapOx chemotherapy OR chemoradiotherapy (54 Gy in 2 Gy fractions with concomitant capecitabine 825 mg/m2 per os bid on radiation days), surgery (10-12 weeks following chemoradiotherapy) and 6 cycles of adjuvant CapOx chemotherapy. A stratification will be performed based on N stage, tumor location in the middle or low rectum and clinical center. Patients with middle or low rectal cancer without distant metastases, with involved circumferential resection margin (based on pretreatment MRI) will be included.
The target accrual is 270 patients in each treatment arm (including 10% potential data loss) based on potential benefit of 12% 3-yr disease-free survival (60% vs 72%), 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 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 0-10 cm above the anal verge
- •No distant metastases
- •Circumferential resection margin (CRM) involvement (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
- •cT2N0M0 rectal cancer
- •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 receive 2 cycles of induction CapOx (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 per os bid days 1-14) chemotherapy, followed by chemoradiotherapy (54 Gy in 2 Gy fractions with concomitant capecitabine 825 mg/m2 per os bid on radiation days), then 2 cycles of consolidation CapOx chemotherapy, surgery (10-12 weeks following chemoradiotherapy) and 2 cycles of adjuvant CapOx chemotherapy
干预措施: Capecitabine (Drug)
Neoadjuvant chemotherapy
Patients receive 2 cycles of induction CapOx (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 per os bid days 1-14) chemotherapy, followed by chemoradiotherapy (54 Gy in 2 Gy fractions with concomitant capecitabine 825 mg/m2 per os bid on radiation days), then 2 cycles of consolidation CapOx chemotherapy, surgery (10-12 weeks following chemoradiotherapy) and 2 cycles of adjuvant CapOx chemotherapy
干预措施: Oxaliplatin (Drug)
Neoadjuvant chemotherapy
Patients receive 2 cycles of induction CapOx (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 per os bid days 1-14) chemotherapy, followed by chemoradiotherapy (54 Gy in 2 Gy fractions with concomitant capecitabine 825 mg/m2 per os bid on radiation days), then 2 cycles of consolidation CapOx chemotherapy, surgery (10-12 weeks following chemoradiotherapy) and 2 cycles of adjuvant CapOx chemotherapy
干预措施: Radiotherapy (Radiation)
Neoadjuvant chemotherapy
Patients receive 2 cycles of induction CapOx (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 per os bid days 1-14) chemotherapy, followed by chemoradiotherapy (54 Gy in 2 Gy fractions with concomitant capecitabine 825 mg/m2 per os bid on radiation days), then 2 cycles of consolidation CapOx chemotherapy, surgery (10-12 weeks following chemoradiotherapy) and 2 cycles of adjuvant CapOx chemotherapy
干预措施: Rectal cancer surgery (Procedure)
Chemoradiotherpy
Patients receive 54 Gy pelvic chemoradiotherapy in 2 Gy fractions with capecitabine 825 mg/m2 bid per os on radiation days and then surgery following 10-12 weeks. After surgery patients receive 6 cycles of adjuvant CapOx chemotherapy.
干预措施: Capecitabine (Drug)
Chemoradiotherpy
Patients receive 54 Gy pelvic chemoradiotherapy in 2 Gy fractions with capecitabine 825 mg/m2 bid per os on radiation days and then surgery following 10-12 weeks. After surgery patients receive 6 cycles of adjuvant CapOx chemotherapy.
干预措施: Oxaliplatin (Drug)
Chemoradiotherpy
Patients receive 54 Gy pelvic chemoradiotherapy in 2 Gy fractions with capecitabine 825 mg/m2 bid per os on radiation days and then surgery following 10-12 weeks. After surgery patients receive 6 cycles of adjuvant CapOx chemotherapy.
干预措施: Radiotherapy (Radiation)
Chemoradiotherpy
Patients receive 54 Gy pelvic chemoradiotherapy in 2 Gy fractions with capecitabine 825 mg/m2 bid per os on radiation days and then surgery following 10-12 weeks. After surgery patients receive 6 cycles of adjuvant CapOx chemotherapy.
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
- 3-year overall survival(3 years)
- Sphincter preservation rate(1 month)
- Adjuvant chemotherapy compliance(6 months)
- local recurrence rate(3 years)
- Preoperative tumor-associated complications rate(6 months)
- Acute chemotherapy toxicity(6 months)
- pathologic complete response rate (pCR)(1 month)
- Operative morbidity(30 days)
研究者
Sergey Gordeyev
Principal Investigator, Consultant surgeon
Blokhin's Russian Cancer Research Center