A Prospective Randomized Controlled Trial of Total Neo-adjuvant Therapy vs Conventional Chemo-radiation Aiming at Increasing Rates of Clinical Complete Response in Locally Advanced Rectal Cancer
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- cCR + PathCR
研究概览
简要总结
Standard therapy for localized rectal cancer includes chemotherapy and radiation therapy, followed by a "recovery" period of 7-12 weeks, surgery and adjuvant chemotherapy for 3-6 months. Even though this protocol achieves high cure rates, many patients need a rectal amputation with placement of definitive colostomies. About 10-20% of patients have a complete clinical response to chemo-radiation and no tumor can be found in the surgical specimen. These patients can be followed with close surveillance and avid surgery. The aim of this study is to evaluate if a strategy including the use of a highly active chemotherapy called "FOLFIRINOX" during the 12 weeks between the end of radiation therapy and evaluation for surgery increases the rates of complete response and, therefore, allows more patients to undergo non-surgical management.
详细描述
Adult patients with locally advanced rectal cancer who have completed conventional long-course chemo-radiation of 54Gy with capecitabine will be randomized 1:1 to a total neo-adjuvant therapy (TNT) protocol or to a control group. Patients in the TNT arm will receive 4 cycles of interval chemotherapy with FOLFIRINOX (5-FU, irinotecan, oxaliplatin) between the end of chemo-radiation and re-staging and those in the control group will undergo standard post-radiation care during this period. All patients will be re-staged with colonoscopy and pelvic MRI 12 weeks after the end of chemo-radiation. Those with a complete clinical response will be placed under a watch-and-wait protocol with digital rectal examinations every 2 months and pelvic MRI and sigmoidoscopy every 6 months. Those wih residual tumors will undergo resection with total mesorectal excision (TME). Patients with a "near complete response", as defined by a multidisciplinary tumor board, will be re-staged at week 16 or 18 after chemo-radiation before undergoing surgery. Adjuvant chemotherapy will be done following the local standard of care.
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
This is an open-label study
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >= 18 y/o
- •Biopsy-confirmed rectal adenocarcinoma
- •Tumor Stage T3+ or N+ M0
- •Adequate liver function (total bilirubin < = 4.0)
- •Adequate kidney function (calculate creatinine-clearance >=30ml/m2/min)
- •Adequate bone marrow function (Platelet counts >=90.000, hemoglobin >=8mg/dl, neutrophile count >= 1.500/cm3)
- •Completed chemo-radiation with at least 54Gy and capecitabine 1650mg/m2/d
排除标准
- •Prior tumor resection
- •Prior radiation to the pelvis
- •Prior chemotherapy for rectal cancer
- •Life expectancy < 6 months
- •Unfit for surgery
- •Need for urgent/ immediate surgery
研究组 & 干预措施
Total neoadjuvant therapy (TNT)
4 cycles of mFOLFIRINOX every 14 days:
- Oxaliplatin 85 mg/m2
- Irinotecan 150mg/m2
- 5-FU 2.400mg/m2
- Dexamethasone 12mg
- Atropine 0.5mg
- Netupitant/palonosetron
干预措施: Folfirinox (Drug)
结局指标
主要结局
cCR + PathCR
时间窗: 12 weeks after the end of chemoradiation
Complete clinical response or pathological response
次要结局
- Overall toxicity(12 weeks)
- Rate of R0 resection(12 weeks)
- Rate of organ preservation(6 months after surgery)