A Multicenter, Randomized Controlled Trial of Preoperative Sequential Short-course Radiation Therapy and Oxaliplatin-based Consolidation Chemotherapy for Locally Advanced Rectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 364
- 试验地点
- 9
- 主要终点
- 3-year disease-free survival
研究概览
简要总结
The treatment protocol proposed in this study is to perform short-term radiation therapy and 4 cycles of FOLFOX chemotherapy for neoadjuvant treatment of locally advanced rectal cancer. Compared to conventional chemoradiation therapy, the preoperative radiotherapy period is shortened, and the cure rate of rectal cancer patients can be improved by early treatment of micrometastasis using systemic chemotherapy. The patients who are assigned to the study group will received the short-course radiotherapy and 4 cycles of FOLFOX and patients in the control will received conventional chemoradiotherapy for preoperative treatment. All patients are recommended to receive total mesorectal excision (TME) after neoadjuvant treatment and adjuvant chemotherapy will be given according to the pathological stage.
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
- 20 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •ECOG (Eastern Cooperative Oncology Group) performance status 0-2
- •Pathologically confirmed rectal cancer (rectal cancer located 10 cm or low from the anal verge in pelvis MRI)
- •Histologic type: adenocarcinoma, mucinous carcinoma, and signet ring cell carcinoma
- •Locally advanced rectal cancer with one or more of the following factors based on pelvis MRI: cTanyN1-2, cT3-4N0, or presence of extramural vascular invasion
- •MRI findings such as pelvic lymph node metastasis, anal sphincter invasion, and T4b are not included in the
排除标准
- •, which cases will be enrolled by the researcher's discretion
- •Patients with appropriate organ (bone marrow, kidney, liver) function
- •A person who understands the study and willing to provide informed consent
- •Exclusion Criteria: (one of the following criteria)
- •Colon cancer or rectal cancer located more than 10 cm from the anal verge
- •Stage I rectal cancer (clinical stage cT1-2N0)
- •Clinically or pathologically diagnosed distant metastasis (cTanyNanyM1)
- •Familial adenomatous polyposis
- •Hereditary nonpolyposis colorectal cancer
- •History of chemotherapy or radiotherapy within 6 months
- •History of colorectal cancer or other type of malignancy within 5 years (except for cured nonmelanoma skin or in situ cervical cancer)
- •Comorbidities that make it difficult to undergo chemotherapy or radiotherapy
- •Bone marrow suppression with neutrophil count <2 ×109/L or platelet count <100 ×109/L prior to the first chemotherapy
- •Peripheral sensory neuropathy with functional impairment (grade 2 or higher)
- •Severe renal dysfunction (GFR ≤30ml/min by Wright or Cockroft formula)
- •Severe hepatic dysfunction
- •Genetic problems such as galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
- •Taking tegafur, gimeracil, and oteracil potassium complex and those within 7 days of discontinuation
- •Taking sorivudine or brivudine
- •Significant heart disease or myocardial infarction within the last 6 months
- •Hereditary diseases or history of coagulopathy
- •Central nervous system disorders with disability or mental disorders
- •Pregnant or lactating women
- •Currently participating in other clinical trials or receiving research medication
- •Unhealed wounds, fractures, peptic ulcer, abscesses in the abdominal cavity
- •Active gastrointestinal bleeding
- •Active infections requiring antibiotics for injection
- •Emergency Surgery
- •History of hypersensitivity to the drugs in study protocol
- •Patients with non-malignant tumor diseases
- •Dihydropyrimidine dehydrogenase deficiency
- •Not willing to participate
研究组 & 干预措施
Study group
Short-course radiotherapy and 4 cycles of mFOLFOX6 followed by TME. Adjuvant chemotherapy will be given according to the pathological stage (CR~pStageI: 6 cycles of capecitabine or 4 cycles of 5-FU with leucovorin, pStageII-III: 8 cycles of mFOLFOX6)
干预措施: short-course radiotherapy (Radiation)
Study group
Short-course radiotherapy and 4 cycles of mFOLFOX6 followed by TME. Adjuvant chemotherapy will be given according to the pathological stage (CR~pStageI: 6 cycles of capecitabine or 4 cycles of 5-FU with leucovorin, pStageII-III: 8 cycles of mFOLFOX6)
干预措施: mFOLFOX6 (Drug)
Study group
Short-course radiotherapy and 4 cycles of mFOLFOX6 followed by TME. Adjuvant chemotherapy will be given according to the pathological stage (CR~pStageI: 6 cycles of capecitabine or 4 cycles of 5-FU with leucovorin, pStageII-III: 8 cycles of mFOLFOX6)
干预措施: TME surgery (Procedure)
Control group
Conventional chemoradiotherapy followed by TME. Adjuvant chemotherapy will be given according to the pathological stage (CR~pStageI: 6 cycles of capecitabine or 4 cycles of 5-FU with leucovorin, pStageII-III: 8 cycles of mFOLFOX6)
干预措施: Chemoradiotherapy (Radiation)
Control group
Conventional chemoradiotherapy followed by TME. Adjuvant chemotherapy will be given according to the pathological stage (CR~pStageI: 6 cycles of capecitabine or 4 cycles of 5-FU with leucovorin, pStageII-III: 8 cycles of mFOLFOX6)
干预措施: TME surgery (Procedure)
结局指标
主要结局
3-year disease-free survival
时间窗: 3 years
To compare the 3-year disease-free survival between the experimental arm and the control arm
次要结局
- R0 resection(within 30 days after TME)
- Incidence of peripheral neuropathy(3 years)
- Loco-regional recurrence(5 years)
- pCR rate(within 30 days after TME)
- Toxicity of neoadjuvant radiotherapy and chemotherapy(6 months)
- Surgical complications(within 60 days after TME)
- European Organization for Research and Treatment of Cancer Quality of Life CR29(2 year after surgery)
- 5-year overall survival(5 years)
- Distant metastasis(5 years)
- European Organization for Research and Treatment of Cancer Quality of Life C30(2 year after surgery)
- The International Index of Erectile Function-5 score, retrograde ejaculation(2 year after surgery)
- 3-year overall survival(3 years)
- TRG(within 30 days after TME)
- Low Anterior Resection Syndrome score(2 year after surgery)
- 5-year disease-free survival(5 years)
研究者
Gyu-Seog Choi
M.D., Ph.D
Kyungpook National University Hospital