Total Neoadjuvant Induction and Consolidation CapeOX Plus Neoadjuvant Intensity Modulated Radiotherapy With Concurrent Capecitabine for MRI Defined High-risk Rectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 81
- 试验地点
- 1
- 主要终点
- Major adverse events
研究概览
简要总结
This study is designed to test the efficacy and safety of total neoadjuvant induction and consolidation CapeOX plus neoadjuvant intensity modulated radiotherapy with concurrent capecitabine for MRI defined high-risk rectal cancer.
详细描述
This phase II trial is studying the efficacy and safety of total neoadjuvant treatment for MRI defined high-risk locally advanced rectal cancer.
MRI imaging features as mrT3c/T3d/T4a/T4b, threatening circumferential resection margin, mrN2 disease or extramural vascular invasion are defined as high-risk factor and proved to associated with unfavorable oncological outcome, especially for distant metastasis. Induction and consolidation chemotherapy plus radiation may increase both systemic and local control. Total neoadjuvant treatment schedule also has advantages as improved patient tolerance, early closure of defunctioning ileostomy etc.
In this study, patients with MRI defined high-risk rectal cancer will receive 3 cycles induction CapeOX, intensity modulated radiotherapy with concurrent capecitabine and 2 cycles consolidation CapeOX and Total mesorectal excision.
The induction chemotherapy related G3-4 toxicity occurred in 42% of patients in GCR-3 trial (23% during RT, 19% during induction chemotherapy). It is hypothesized that the neoadjuvant chemotherapy related G3-4 toxicity rate of the present regimen will be lower than 25% (10% during IMRT, 15% during induction/consolidation chemotherapy). A sample size of 67 achieves 80% power to detect a difference (△P =17%, P1=25%, P0=42%) using a one-sided binomial test. (α= 0.05). If the number of G3-4 toxic event is 21 or less, the hypothesis that P1>= 42% is rejected. About 10 % loss to follow-up was anticipated, so an additional eight patients will be recruited. The study requires 75 subjects in all.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Age ≥ 18 years and ≤75 years.
- •ECOG Performance status 0-
- •Histologically confirmed diagnosis of adenocarcinoma of the rectum.
- •The distance from down verge of tumor to anal-rectal junction (ARJ) ≤8cm based on MRI, or ≤12 cm based on sigmoidoscopy.
- •Clinical Stage T3c, T3d, T4a or T4b, or EMVI (+) or mrN2 or CRM (+) based on MRI.
- •No evidence of distant metastases.
- •No prior pelvic radiation therapy.
- •No prior chemotherapy or surgery for rectal cancer.
- •No active infections requiring systemic antibiotic treatment.
- •ANC > 1.5 cells/mm3, HGB > 10.0 g/dL, PLT > 100,000/mm3, total bilirubin ≤ 1.5 x ULN, AST≤ 3 x ULN, ALT ≤ 3 x ULN.
- •Patients must read, agree to, and sign a statement of Informed Consent prior to participation in this study.
排除标准
- •Recurrent rectal cancer.
- •Anticipated unresectable tumor after neoadjuvant treatment.
- •Creatinine level greater than 1.5 times the upper limit of normal.
- •Patients who have received prior pelvic radiotherapy.
- •Patients who are unable to undergo an MRI.
- •Patients with a history of a prior malignancy within the past 5 years, except for adequately treated basal cell or squamous cell skin cancer.
- •Patients with a history of any arterial thrombotic event within the past 6 months. This includes angina (stable or unstable), MI, TIA, or CVA.
- •Other Anticancer or Experimental Therapy.
- •Women who are pregnant or breast-feeding.
- •Patients with any other concurrent medical or psychiatric condition or disease which would make them inappropriate candidates for entry into this study.
研究组 & 干预措施
TNT
Patients with MRI defined high-risk rectal cancer will receive chemotherapy before and after chemoradiation, and will not receive adjuvant treatment. This arm is called total neoadjuvant treatment (TNT). The neoadjuvant chemotherapy regimen is designed as 3 cycles of CapeOX (Capecitabine+Oxaliplatin) over a period of approximately 8 weeks. Tumor response will be evaluated after chemotherapy. Then patients will undergo 22f-IMRT (Intensity modulated radiotherapy) with capecitabine. Patients will receive two more cycles of consolidation CapeOX if tolerable when there was no progressed disease in induction CapeOX.
Finally, patients will receive TME (Total mesorectal excision) following TNT if no metastasis occurs.
干预措施: Oxaliplatin (Drug)
TNT
Patients with MRI defined high-risk rectal cancer will receive chemotherapy before and after chemoradiation, and will not receive adjuvant treatment. This arm is called total neoadjuvant treatment (TNT). The neoadjuvant chemotherapy regimen is designed as 3 cycles of CapeOX (Capecitabine+Oxaliplatin) over a period of approximately 8 weeks. Tumor response will be evaluated after chemotherapy. Then patients will undergo 22f-IMRT (Intensity modulated radiotherapy) with capecitabine. Patients will receive two more cycles of consolidation CapeOX if tolerable when there was no progressed disease in induction CapeOX.
Finally, patients will receive TME (Total mesorectal excision) following TNT if no metastasis occurs.
干预措施: Capecitabine (Drug)
TNT
Patients with MRI defined high-risk rectal cancer will receive chemotherapy before and after chemoradiation, and will not receive adjuvant treatment. This arm is called total neoadjuvant treatment (TNT). The neoadjuvant chemotherapy regimen is designed as 3 cycles of CapeOX (Capecitabine+Oxaliplatin) over a period of approximately 8 weeks. Tumor response will be evaluated after chemotherapy. Then patients will undergo 22f-IMRT (Intensity modulated radiotherapy) with capecitabine. Patients will receive two more cycles of consolidation CapeOX if tolerable when there was no progressed disease in induction CapeOX.
Finally, patients will receive TME (Total mesorectal excision) following TNT if no metastasis occurs.
干预措施: Intensity modulated radiotherapy (Radiation)
TNT
Patients with MRI defined high-risk rectal cancer will receive chemotherapy before and after chemoradiation, and will not receive adjuvant treatment. This arm is called total neoadjuvant treatment (TNT). The neoadjuvant chemotherapy regimen is designed as 3 cycles of CapeOX (Capecitabine+Oxaliplatin) over a period of approximately 8 weeks. Tumor response will be evaluated after chemotherapy. Then patients will undergo 22f-IMRT (Intensity modulated radiotherapy) with capecitabine. Patients will receive two more cycles of consolidation CapeOX if tolerable when there was no progressed disease in induction CapeOX.
Finally, patients will receive TME (Total mesorectal excision) following TNT if no metastasis occurs.
干预措施: Total mesorectal excision (Procedure)
结局指标
主要结局
Major adverse events
时间窗: 3 years
Adverse events will be graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
次要结局
- Disease-free survival (DFS)(3 years)
- Pathological downstaging rate(1 year)
- Compliance rate with neoadjuvant treatment schedule(1 year)
- European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30)(Time0: before neoadjuvant treatment; Time1: at 4 months after the completion of neoadjuvant radiation; Time2: 12 months after Time1; Time3: 24 months after Time1; Time4: 36 months after Time1)
- European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Colorectal Cancer Module 29 (EORTC QLQ-CR29)(Time0: before neoadjuvant treatment; Time1: at 4 months after the completion of neoadjuvant radiation; Time2: 12 months after Time1; Time3: 24 months after Time1; Time4: 36 months after Time1)
研究者
Aiwen Wu
Chief, Unit III & Ostomy Service, Gastrointestinal Cancer Center
Peking University Cancer Hospital & Institute