A Study of Avastin (Bevacizumab) in Combination With mFOLFOX-6 or FOLFOXIRI in Patients With Metastatic Colorectal Cancer.
2016年11月1日 更新者：Hoffmann-La Roche
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)
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.
研究概览
地位
完全的
条件
研究类型
介入性
注册 (实际的)
80
阶段
- 阶段2
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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Wien、奥地利、1090
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Bordeaux、法国、33075
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Creteil、法国、94010
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Le Mans、法国、72037
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Lille、法国、59037
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Lyon、法国、69373
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Montpellier、法国、34298
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Villejuif、法国、94804
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London、英国、WC1E 6DD
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Manchester、英国、M20 4QL
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Sutton、英国、SM2 5PT
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Wirral、英国、CH63 4JY
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Girona、西班牙、17007
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Madrid、西班牙、28046
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Madrid、西班牙、28007
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Valencia、西班牙、46026
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Guipuzcoa
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San Sebastian、Guipuzcoa、西班牙、20080
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Islas Baleares
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Palma de Mallorca、Islas Baleares、西班牙、07198
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La Coruña
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Santiago de Compostela、La Coruña、西班牙、15706
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 及以上 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的：1个
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85mg/m2 2 小时静脉输注，每 2 周第 1 天
200mg/m2 2 小时静脉输注，每 2 周第 1 天
2400mg/m2 46 小时连续静脉输注，每 2 周第 1 天
Bolus 400mg/m2, day 1 every 2 weeks
3200mg/m2 46-hour continuous iv infusion, day 1 every 2 weeks
400mg/m2 2-hour iv infusion, day 1 every 2 weeks
5mg/kg iv day 1 every 2 weeks
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有源比较器：2个
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85mg/m2 2 小时静脉输注，每 2 周第 1 天
200mg/m2 2 小时静脉输注，每 2 周第 1 天
2400mg/m2 46 小时连续静脉输注，每 2 周第 1 天
Bolus 400mg/m2, day 1 every 2 weeks
3200mg/m2 46-hour continuous iv infusion, day 1 every 2 weeks
400mg/m2 2-hour iv infusion, day 1 every 2 weeks
5mg/kg iv day 1 every 2 weeks
165mg/m2 1-hour iv infusion, day 1 every 2 weeks
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Percentage of Participants With Complete Resection or Residual (Microscopic or Macroscopic) Tumor
大体时间：Up to 5 years (at Screening; every 6 weeks, and within 4 weeks prior to surgery; and at time of/after surgery)
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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.
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Up to 5 years (at Screening; every 6 weeks, and within 4 weeks prior to surgery; and at time of/after surgery)
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Time to Resection
大体时间：Up to 5 years (at Screening; prior to each cycle, and within 7 days prior to surgery; and at time of surgery)
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Time to resection was defined as the time from randomization to the date of first resective surgery.
For participants who did not undergo resective surgery, time to resection was censored at Day 1.
Time to resection was estimated by Kaplan-Meier analysis.
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Up to 5 years (at Screening; prior to each cycle, and within 7 days prior to surgery; and at time of surgery)
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Percentage of Participants With Histopathological Response
大体时间：Up to 5 years (at Screening; every 6 weeks, and within 4 weeks prior to surgery; and at time of/after surgery)
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At the time of resective surgery, participants were evaluated for histopathological response as defined through pathologist review of the resected metastatic lesions, including assessment of margin status and tumor cell viability.
Histopathological response classification was based upon the percentage of viable tumor cells, where 'Complete response' was considered for those with 0 percent (%) viable tumor cells, 'Major response' for those with 1% to 49% viable tumor cells, 'Minor response' for 50% to 99% viable tumor cells, and 'No response' for 100% viable tumor cells.
The response could not be determined in some cases and was documented as 'Unknown.'
The percentage of participants within each response category was calculated as [number of participants with a given response divided by the number of participants who completed the assessment] multiplied by 100.
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Up to 5 years (at Screening; every 6 weeks, and within 4 weeks prior to surgery; and at time of/after surgery)
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Percentage of Participants With Complete or Major Histopathological Response
大体时间：Up to 5 years (at Screening; every 6 weeks, and within 4 weeks prior to surgery; and at time of/after surgery)
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At the time of resective surgery, participants were evaluated for histopathological response as defined through pathologist review of the resected metastatic lesions, including assessment of margin status and tumor cell viability.
Histopathological response classification was based upon the percentage of viable tumor cells, as described previously.
The collective percentage of participants assessed as having a complete or major response was calculated as [number of participants with complete or major response divided by the number of participants who completed the assessment] multiplied by 100.
Associated 95% confidence intervals were calculated for one-sample binomial using the Clopper-Pearson method.
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Up to 5 years (at Screening; every 6 weeks, and within 4 weeks prior to surgery; and at time of/after surgery)
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Percentage of Participants Experiencing Relapse Following Curative Resection
大体时间：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)
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Among participants with curative resection (complete resection [R0] or microscopic residual tumor [R1]), relapse was defined as the first new occurrence of cancer or death.
The percentage of participants who experienced relapse was calculated as [number of participants with a relapse event divided by the number of participants initially classified as R0 or R1 following resective surgery] multiplied by 100.
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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)
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Relapse-Free Survival (RFS)
大体时间：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)
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RFS was defined as the time from curative resection (complete resection [R0] or microscopic residual tumor [R1]) to the date of first diagnosis of relapse.
For participants with curative resection and without relapse, RFS was censored at the last known relapse-free assessment.
RFS was estimated by Kaplan-Meier analysis.
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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)
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Percentage of Participants Experiencing Death or Disease Progression
大体时间：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)
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PD was defined, using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, as at least a 20% increase in the sum of the longest diameter of target lesions, or the appearance of one or more new lesions.
The percentage of participants experiencing PD or death was calculated as [number of participants with event divided by the number of participants analyzed] multiplied by 100.
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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)
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Progression-Free Survival (PFS)
大体时间：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)
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PFS was defined, using RECIST version 1.0, as the time from randomization to the date of first documented PD or death from any cause.
PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions, or the appearance of one or more new lesions.
For participants without documented PD or death, PFS was censored at the time of last tumor assessment.
PFS was estimated by Kaplan-Meier analysis.
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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)
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Percentage of Participants Who Died
大体时间：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)
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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)
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Overall Survival (OS)
大体时间：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)
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OS was defined as the time from randomization to death from any cause.
For participants without an event of death, OS was censored at the last-known alive date.
OS was estimated by Kaplan-Meier analysis.
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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)
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Percentage of Participants With a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR) According to RECIST Version 1.0
大体时间：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)
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Using RECIST version 1.0, participants were considered to have achieved CR upon the disappearance of all target and non-target lesions.
Participants who achieved PR demonstrated at least a 30% decrease in the sum of the largest diameter of target lesions, taking as reference the Screening sum largest diameter.
Responses were confirmed by repeat assessments no less than 4 weeks after criteria for response were first met.
The collective percentage of participants with confirmed best overall response of CR or PR was calculated as [number of participants meeting RECIST criteria for CR or PR divided by the number of participants analyzed] multiplied by 100.
Associated 95% confidence intervals were calculated for one-sample binomial using the Clopper-Pearson method.
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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)
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Time to Response
大体时间：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)
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Time to response according to RECIST version 1.0 was defined as the time from randomization to the date of first documented CR or PR.
Participants were considered to have achieved CR upon the disappearance of all target and non-target lesions.
Participants who achieved PR demonstrated at least a 30% decrease in the sum of the largest diameter of target lesions, taking as reference the Screening sum largest diameter.
Responses were confirmed by repeat assessments no less than 4 weeks after criteria for response were first met.
For participants who did not complete a confirmatory tumor assessment, time to response was censored at the date of last tumor assessment, or if unavailable, at the date of first dose.
Time to response was estimated by Kaplan-Meier analysis.
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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)
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Percentage of Participants With Complications Related to First Resective Surgery
大体时间：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)
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Complications related to the first resective surgery were evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0, and classified according to severity.
The NCI-CTCAE severity classification criteria are as follows: Grade 5 equals (=) resulting in death; Grade 4 = life-threatening; Grade 3 = severe; Grade 2 = moderate; and Grade 1 = mild.
The percentage of participants experiencing a given adverse event (AE) by severity grade was calculated as [number of participants with an AE divided by the number of participants who underwent first resective surgery] multiplied by 100.
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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)
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Percentage of Participants With Complications Related to Second Resective Surgery
大体时间：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)
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Complications related to the second resective surgery were evaluated using the NCI-CTCAE version 3.0, and classified according to severity.
The NCI-CTCAE severity classification criteria are as follows: Grade 5 = resulting in death; Grade 4 = life-threatening; Grade 3 = severe; Grade 2 = moderate; and Grade 1 = mild.
The percentage of participants experiencing a given AE by severity grade was calculated as [number of participants with an AE divided by the number of participants who underwent second resective surgery] multiplied by 100.
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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)
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
- Cremolini C, Antoniotti C, Stein A, Bendell J, Gruenberger T, Rossini D, Masi G, Ongaro E, Hurwitz H, Falcone A, Schmoll HJ, Di Maio M. Individual Patient Data Meta-Analysis of FOLFOXIRI Plus Bevacizumab Versus Doublets Plus Bevacizumab as Initial Therapy of Unresectable Metastatic Colorectal Cancer. J Clin Oncol. 2020 Aug 20:JCO2001225. doi: 10.1200/JCO.20.01225. Online ahead of print.
- Gruenberger T, Bridgewater J, Chau I, Garcia Alfonso P, Rivoire M, Mudan S, Lasserre S, Hermann F, Waterkamp D, Adam R. Bevacizumab plus mFOLFOX-6 or FOLFOXIRI in patients with initially unresectable liver metastases from colorectal cancer: the OLIVIA multinational randomised phase II trial. Ann Oncol. 2015 Apr;26(4):702-708. doi: 10.1093/annonc/mdu580. Epub 2014 Dec 23.
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2008年10月1日
初级完成 (实际的)
2013年10月1日
研究完成 (实际的)
2013年10月1日
研究注册日期
首次提交
2008年10月22日
首先提交符合 QC 标准的
2008年10月22日
首次发布 (估计)
2008年10月23日
研究记录更新
最后更新发布 (估计)
2016年11月2日
上次提交的符合 QC 标准的更新
2016年11月1日
最后验证
2016年11月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.
奥沙利铂的临床试验
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Hospices Civils de Lyon未知