Phase III Study of Neoadjuvant Chemotherapy With Capecitabine and Oxaliplatin Versus Chemoradiation for Locally Advanced Rectal Cancer Patients
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 663
- 试验地点
- 1
- 主要终点
- Local-regional failure-free survival
研究概览
简要总结
Although neoadjuvant radiotherapy greatly decreases local recurrence in locally advanced rectal cancer patients undergoing surgery, it inevitably results in short-term and long-term toxicities. More importantly, it has not been confirmed that neoadjuvant radiotherapy could improve overall survival. The purpose of this study is to compare the effects of chemotherapy alone using a combination regimen known as XELOX (capecitabine and oxaliplatin ) and selective use of the standard treatment to the standard treatment of chemotherapy and radiation.
详细描述
This randomised, open-label, multicentre,phase 3 trial began in August, 2014, as an adjuvant trial comparing capecitabine-based neoadjuvant chemoradiotherapy with chemotherapy alone,in patients aged 18 years to 75 with clinical stage II-III locally advanced rectal cancer from six Chinese institutions.
Patients with local advanced rectal cancer (T2N+ or T3-4aNany,M0, CRM≥2mm, 12cm from the anus verge) were scheduled to Group A: receive neoadjuvant chemotherapy alone (4 cycles of XELOX: oxaliplatin 130mg/m2 day 1，capecitabine 2000mg/m2 days 1-14, repeated every 21 days) followed by radical surgery and 4 cycles of XELOX ( oxaliplatin 130mg/m2 day 1，capecitabine 2000mg/m2 days 1-14, repeated every 21 days) and Group B :chemoradiotherapy (50.4 Gy plus capecitabine 1650 mg/m² administered orally and concurrently with radiation therapy for 5 days per week.) followed by radical surgery and 6 cycles of XELOX ( oxaliplatin 130mg/m2 day 1，capecitabine 2000mg/m2 days 1-14, repeated every 21 days) The primary endpoint was 3-year local recurrence free survival; analyses were done based on all patients with post-randomization data.
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
- •DISEASE CHARACTERISTICS:
- •Diagnosis of rectal adenocarcinoma
- •Radiologically measurable or clinically evaluable disease
- •Tumor location within 12cm from anal verge
- •Clinical stage T2N+ or T3-4aNany,M0 Clinical staging should be estimated based on the combination of the following assessments: physical examination by the primary surgeon, CT scan of the chest/abdomen/pelvis, and a pelvic MRI with or without an endorectal ultrasound (ERUS)
- •No evidence that tumor is adjacent to (defined as within 2 mm of) the mesorectal fascia on pre-operative MRI
- •No tumor causing symptomatic bowel obstruction
- •No distant metastasis
- •PATIENT CHARACTERISTICS:
- •ECOG performance status 0, 1
- •White Blood Cell (WBC) ≥ 4,000/mm³
- •Platelets ≥ 100,000/mm³
- •Hemoglobin > 10.0 g/dL
- •Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •AST and ALT ≤ 1.5 times ULN
- •Creatinine ≤ 1.5 times ULN
- •No co-morbid illnesses or other concurrent disease that, in the judgment of the clinician obtaining informed consent, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
排除标准
- •Pregnant or nursing
- •Patient of child-bearing potential is not willing to employ adequate contraception
- •Not willing to return to enrolling medical site for all study assessments
- •With other invasive malignancy ≤ 5 years prior to registration; exceptions are colonic polyps, non-melanoma skin cancer, or carcinoma-in-situ of the cervix
- •Chemotherapy within 5 years prior to registration (hormonal therapy is allowable if the disease-free interval is ≥ 5 years)
- •Prior pelvic radiation
研究组 & 干预措施
Chemotherapy
Patients receive neoadjuvant chemotherapy comprising oxaliplatin 130mg/m² ivdrip over 2 hours on day 1,capecitabine 2000 mg/m² on days 1-14, treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.Patients without disease progression undergo low-anterior resection (LAR) with total mesorectal excision (TME) and 4 cycles of XELOX ( oxaliplatin 130mg/m² day 1，capecitabine 2000mg/m² days 1-14, repeated every 21 days). Patients with disease progression undergo chemoradiation as in group chemoradiotherapy before proceeding to LAR with TME.
干预措施: Oxaliplatin (Drug)
Chemotherapy
Patients receive neoadjuvant chemotherapy comprising oxaliplatin 130mg/m² ivdrip over 2 hours on day 1,capecitabine 2000 mg/m² on days 1-14, treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.Patients without disease progression undergo low-anterior resection (LAR) with total mesorectal excision (TME) and 4 cycles of XELOX ( oxaliplatin 130mg/m² day 1，capecitabine 2000mg/m² days 1-14, repeated every 21 days). Patients with disease progression undergo chemoradiation as in group chemoradiotherapy before proceeding to LAR with TME.
干预措施: capecitabine (Drug)
Chemoradiotherapy
Patients receive capecitabine 825 mg/m² twice daily concurrently with radiation therapy for 5 days per week. Patients also undergo intensity-modulated radiation therapy 5 days a week for approximately 5.5 weeks. Patients then undergo LAR with TME and 4 cycles of XELOX ( oxaliplatin 130mg/m² day 1，capecitabine 2000mg/m² days 1-14, repeated every 21 days) .
干预措施: capecitabine (Drug)
Chemoradiotherapy
Patients receive capecitabine 825 mg/m² twice daily concurrently with radiation therapy for 5 days per week. Patients also undergo intensity-modulated radiation therapy 5 days a week for approximately 5.5 weeks. Patients then undergo LAR with TME and 4 cycles of XELOX ( oxaliplatin 130mg/m² day 1，capecitabine 2000mg/m² days 1-14, repeated every 21 days) .
干预措施: Radiation (Radiation)
结局指标
主要结局
Local-regional failure-free survival
时间窗: Up to 5 years
the time interval between the date of randomization and the date of local or regional progression/relapse, or death, whichever occurred first.regional progression/relapse, or death, whichever occurred first.
次要结局
- Disease free survival(Up to 5 years)
- Pathologic complete response and tumor regression grade(Up to 18 weeks)
- Pelvic R0 resection rate(Up to 18 weeks)
- Overall survival(Up to 5 years)
- Adverse event (AE) profiles(Up to 5 years)
- Rate of receiving pre-operative or post-operative chemoradiation(Up to 30 weeks)
研究者
Pei-Rong Ding
Associate Professor
Sun Yat-sen University