Phase III Trial of Infusional Fluorouracil, Leucovorin, Oxaliplatin and Irinotecan (FOLFOXIRI) Compared With Infusional Fluorouracil, Leucovorin and Irinotecan (FOLFIRI) as First-line Treatment for Metastatic Colorectal Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 244
- 试验地点
- 48
- 主要终点
- Response rate (RR)
研究概览
简要总结
The purpose of the study is to evaluate if the exposure to all the three active cytotoxic agents (FOLFOXIRI regimen) is superior in terms of response rate to conventional chemotherapy with the FOLFIRI regimen as first-line treatment of metastatic colorectal cancer patients.
详细描述
Survival of patients with metastatic colorectal cancer is correlated with the proportion of patients who receive all the three active drugs in the course of the disease, but not with the proportion of patients who receive any second-line therapy. In a sequential strategy, not all patients who progress after first-line chemotherapy are able to receive second-line treatment. Moreover, there is a correlation between the response rate to chemotherapy and the postchemotherapy radical resection rate of metastases.
Therefore, a way to improve the outcome of metastatic colorectal cancer patients could be to administer a first-line regimen containing the three active agents.
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
- •adenocarcinoma of the colon or rectum
- •unresectable metastatic disease
- •age 18 to 75 years
- •Eastern Cooperative Oncology Group (ECOG) performance status of 2 or lower if age 70 years or younger or ECOG performance status of 0 if age 71 to 75 years measurable disease according to WHOcriteria
- •leukocyte count of at least 3,500/mm3, neutrophils count of at least 1,500/mm3, platelet count of at least 100,000/mm3
- •serum creatinine of 1.3 mg/dL or less
- •serum bilirubin less than 1.5 mg/dL and AST, ALT, and alkaline phosphatase 2.5 x normal values or less (</= 5 if liver metastases)
- •previous fluoropyrimidine-based adjuvant chemotherapy was allowed if ended more than 6 months before random assignment
排除标准
- •previous palliative chemotherapy for metastatic disease
- •previous chemotherapy including irinotecan or oxaliplatin
- •symptomatic cardiac disease, myocardial infarction in the last 24 months or uncontrolled arrhythmia
- •active infections
- •inflammatory bowel disease
- •total colectomy
研究组 & 干预措施
FOLFIRI
Irinotecan 180 mg/sqm on day 1 Leucovorin 100 mg/sqm on day 1 and day 2 5-fluorouracil 400 mg/sqm bolus followed by 5-fluorouracil 600 mg/sqm 22-hour continuous infusion on day 1 and day 2 Repeated every 2 weeks
干预措施: FOLFIRI (Drug)
FOLFOXIRI
Irinotecan 165 mg/sqm on day 1 Oxaliplatin 85 mg/sqm on day 1 Leucovorin 200 mg/sqm on day 1 5-fluorouracil 3200 mg/sqm 48-hour continuous infusion starting on day 1 Repeated every 2 weeks
干预措施: FOLFOXIRI (Drug)
结局指标
主要结局
Response rate (RR)
时间窗: Responses are evaluated every 8 weeks according to WHO criteria and reviewed by an independent panel at the end of treatment (6 months)
Responses are evaluated every 8 weeks according to WHO criteria. The determination of responses and progression was initially based on investigator-reported measurements; computed tomography scans of all responding patients and of patients with stable disease were subsequently subjected to external review by an independent panel.
次要结局
- Postchemotherapy radical (R0) surgical resection rate of metastases(Postchemotherapy radical (R0) surgical resection rate of metastases were evaluated every 8 weeks during treatment and during follow up (36 months))
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability(Number of Participants with Adverse Events as a Measure of Safety and Tolerability were evaluated every 2 weeks during treatment and every 8 weeks during follow up (36 months))
- Progression-free survival (PFS)(Progressions are evaluated every 8 weeks according to WHO criteria and reviewed by an independent panel at the end of follow up (36 months))
- Overall survival (OS)(For survival analysis participants are followed until death)
- Quality of life (QoL)(Quality of life was evaluated every 2 weeks during treatment and every 8 weeks during follow up (36 months))