A Multicentre Randomised Phase II Study to Assess the Safety and Resectability in Patients With Initially Unresectable Liver Metastases Secondary to Colorectal Cancer Receiving First-line Treatment Either With mFOLFOX-6 Plus Bevacizumab or FOLFOXIRI Plus Bevacizumab (OLIVIA)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 80
- 主要终点
- Percentage of Participants With Complete Resection or Residual (Microscopic or Macroscopic) Tumor
研究概览
简要总结
This 2 arm study will compare the resection rate of liver metastases and safety of surgery in patients with metastatic colorectal cancer and primarily unresectable liver metastases receiving treatment with Avastin in combination with 5-FU, leucovorin and oxaliplatin with irinotecan (FOLFOXIRI) or without irinotecan (mFOLFOX-6) as first line treatment. Patients will be randomized to receive Avastin (5mg/kg iv every 2 weeks) in combination with each of these two standard neoadjuvant chemotherapy regimens. The anticipated time on study treatment is until surgery, disease progression, unacceptable toxicity or patient refusal, and the target sample size is <100 individuals.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •adult patients, >=18 years of age;
- •unresectable liver metastasis secondary to cancer of colon or rectum;
- •scheduled for standard first line chemotherapy;
- •ECOG performance score of 0 or 1;
- •condition feasible for major abdominal surgery after first line treatment.
排除标准
- •diagnosis of metastatic disease >3 months prior to study entry;
- •evidence of extrahepatic disease, diffuse peritoneal carcinosis or involvement of celiac lymph nodes;
- •prior systemic or local treatment of metastatic disease;
- •prior (neo)adjuvant chemotherapy/radiotherapy completed within 6 months prior to study entry;
- •history or evidence of CNS disease unrelated to cancer.
研究组 & 干预措施
1
干预措施: 5-FU (Drug)
1
干预措施: Leucovorin (Drug)
1
干预措施: Oxaliplatin (Drug)
1
干预措施: bevacizumab [Avastin] (Drug)
2
干预措施: 5-FU (Drug)
2
干预措施: Irinotecan (Drug)
2
干预措施: Leucovorin (Drug)
2
干预措施: Oxaliplatin (Drug)
2
干预措施: bevacizumab [Avastin] (Drug)
结局指标
主要结局
Percentage of Participants With Complete Resection or Residual (Microscopic or Macroscopic) Tumor
时间窗: Up to 5 years (at Screening; every 6 weeks, and within 4 weeks prior to surgery; and at time of/after surgery)
Following resective surgery, participants were evaluated for complete resection (R0) or the presence of microscopic (R1) or macroscopic (R2) residual tumor. The percentage of participants within each residual tumor classification was calculated as \[number of participants with R0, R1, and/or R2 divided by the total number of participants\] multiplied by 100. Associated 95% confidence intervals were calculated for one-sample binomial using the Clopper-Pearson method.
次要结局
- Time to Resection(Up to 5 years (at Screening; prior to each cycle, and within 7 days prior to surgery; and at time of surgery))
- Percentage of Participants With Histopathological Response(Up to 5 years (at Screening; every 6 weeks, and within 4 weeks prior to surgery; and at time of/after surgery))
- Percentage of Participants With Complete or Major Histopathological Response(Up to 5 years (at Screening; every 6 weeks, and within 4 weeks prior to surgery; and at time of/after surgery))
- Percentage of Participants Experiencing Relapse Following Curative Resection(Up to 5 years (at time of surgery; 48 hours and 4 and 12 weeks after surgery; within 4 weeks after completion of treatment; every 3 to 6 months for 1 year; then annually))
- Relapse-Free Survival (RFS)(Up to 5 years (at time of surgery; 48 hours and 4 and 12 weeks after surgery; within 4 weeks after completion of treatment; every 3 to 6 months for 1 year; then annually))
- Percentage of Participants Experiencing Death or Disease Progression(Up to 5 years (at Screening; every 6 weeks, and within 4 weeks prior to surgery; 4 and 12 weeks after surgery; and at the end of Cycles 4 and 8 if assessed as R0 or R1, or every 6 weeks until progression or resectability if assessed as R2))
- Progression-Free Survival (PFS)(Up to 5 years (at Screening; every 6 weeks, and within 4 weeks prior to surgery; 4 and 12 weeks after surgery; and at the end of Cycles 4 and 8 if assessed as R0 or R1, or every 6 weeks until progression or resectability if assessed as R2))
- Percentage of Participants Who Died(Up to 5 years (prior to each cycle, and within 7 days prior to surgery; at time of surgery; 48 hours and 4 and 12 weeks after surgery; within 4 weeks after completion of treatment; every 3 to 6 months for 1 year; then annually))
- Overall Survival (OS)(Up to 5 years (prior to each cycle, and within 7 days prior to surgery; at time of surgery; 48 hours and 4 and 12 weeks after surgery; within 4 weeks after completion of treatment; every 3 to 6 months for 1 year; then annually))
- Percentage of Participants With a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR) According to RECIST Version 1.0(Up to 5 years (at Screening; every 6 weeks, and within 4 weeks prior to surgery; 4 and 12 weeks after surgery; and at the end of Cycles 4 and 8 if assessed as R0 or R1, or every 6 weeks until progression or resectability if assessed as R2))
- Time to Response(Up to 5 years (at Screening; every 6 weeks, and within 4 weeks prior to surgery; 4 and 12 weeks after surgery; and at the end of Cycles 4 and 8 if assessed as R0 or R1, or every 6 weeks until progression or resectability if assessed as R2))
- Percentage of Participants With Complications Related to First Resective Surgery(Up to 5 years (at time of surgery; 48 hours and 4 and 12 weeks after surgery; within 4 weeks after completion of treatment; every 3 to 6 months for 1 year; then annually))
- Percentage of Participants With Complications Related to Second Resective Surgery(Up to 5 years (at time of surgery; 48 hours and 4 and 12 weeks after surgery; within 4 weeks after completion of treatment; every 3 to 6 months for 1 year; then annually))