Combination Chemotherapy With or Without Cetuximab Before and After Surgery in Treating Patients With Resectable Liver Metastases Caused By Colorectal Cancer
A Prospective Randomised Open Label Trial of Oxaliplatin/Fluoropyrimidine Versus Oxaliplatin/Fluoropyrimidine Plus Cetuximab Pre and Post Operatively in Patients With Resectable Colorectal Liver Metastasis Requiring Chemotherapy
RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, fluorouracil, leucovorin, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving combination chemotherapy together with monoclonal antibodies before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery. It is not yet known whether combination chemotherapy is more effective with or without cetuximab in treating liver metastases caused by colorectal cancer.
PURPOSE: This randomized phase III trial is studying combination chemotherapy to compare how well it works when given with or without cetuximab before and after surgery in treating patients with resectable liver metastases caused by colorectal cancer.
研究概览
地位
详细说明
OBJECTIVES:
Primary
- Compare progression-free survival of patients with resectable colorectal liver metastases treated with neoadjuvant and adjuvant combination chemotherapy with vs without cetuximab.
Secondary
- Compare the overall survival of patients treated with these regimens.
- Compare the quality of life of patients treated with these regimens.
- Compare the cost effectiveness of these regimens in these patients.
OUTLINE: This is a prospective, randomized, multicenter, open-label study. Patients are stratified according to participating center and assigned chemotherapy regimen. Patients are randomized to 1 of 2 treatment arms.
Neoadjuvant therapy:
Arm I: Patients receive 1 of the following chemotherapy regimens:
- OxMdG: Patients receive leucovorin calcium IV over 2 hours and oxaliplatin IV over 2 hours on day 1. Patients also receive fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
- CAPOX: Patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-14. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Arm II: Patients receive 1 of the following regimens:
- OxMdG + cetuximab: Patients receive cetuximab IV over 1-2 hours on day 1 and OxMdG chemotherapy as in arm I. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
- CAPOX + cetuximab: Patients receive cetuximab IV over 1-2 hours on days 1, 8, and 15 and CAPOX chemotherapy as in arm I. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
- Surgery: Beginning 2-6 weeks after completion of chemotherapy, patients in both arms undergo liver resection.
Adjuvant therapy: Beginning 4-8 weeks after completion of surgery, patients receive treatment (OxMdG or CAPOX with or without cetuximab) as in arm I or II of neoadjuvant therapy.
- Arm I: Treatment with OxMdG repeats every 2 weeks for up to 6 courses and treatment with CAPOX repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
- Arm II: Treatment with OxMdG + cetuximab repeats every 2 weeks for up to 6 courses and treatment with CAPOX + cetuximab repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Quality of life is assessed at baseline, every 12 weeks during chemotherapy, at completion of study treatment, every 3 months for 1 year, and then every 6 months thereafter.
Cost per life year and per quality-adjusted life year is assessed at baseline, every 12 weeks during treatment, and then at 3, 5, and 10 years.
After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years.
Peer Reviewed and Funded or Endorsed by Cancer Research UK
研究类型
注册 (预期的)
阶段
- 第三阶段
联系人和位置
学习联系方式
- 姓名:Louisa Little
- 电话号码:02380795154
学习地点
-
-
England
-
Basildon、England、英国、SS16 5NL
- 招聘中
- Basildon University Hospital
-
接触:
- Pauline Leonard, MD
- 电话号码:44-1702-435-555
-
Basingstoke、England、英国、RG24 9NA
- 招聘中
- Basingstoke and North Hampshire NHS Foundation Trust
-
接触:
- Charlotte Rees, MD
- 电话号码:44-125-631-4793
-
Bournemouth、England、英国、BH7 7DW
- 招聘中
- Royal Bournemouth Hospital
-
接触:
- Tamas Hickish, MD
- 电话号码:44-1202-303-626
- 邮箱:tamas.hickish@rbch.nhs.uk
-
Cambridge、England、英国、CB2 0QQ
- 招聘中
- Addenbrooke's Hospital
-
接触:
- Pippa Corrie, PhD, FRCP
- 电话号码:44-1223-274-401
- 邮箱:pippa.corrie@addenbrookes.nhs.uk
-
Guildford、England、英国、GU2 7XX
- 招聘中
- St. Luke's Cancer Centre at Royal Surrey County Hospital
-
接触:
- Sharadah Essapen, MD
- 电话号码:44-1483-571-122
-
Liverpool、England、英国、L9 7AL
- 招聘中
- Aintree University Hospital
-
接触:
- Graeme J. Poston, MD
- 电话号码:44-151-525-5980
- 邮箱:graeme.poston@aintree.nhs.uk
-
Liverpool、England、英国、L9 7AL
- 招聘中
- Royal Liverpool University Hospital
-
接触:
- Paula Ghaneh, MD
-
London、England、英国、SW3 6JJ
- 招聘中
- Royal Marsden - London
-
接触:
- David Cunningham, MD
- 电话号码:44-20-8661-3156
-
London、England、英国、EC1A 7BE
- 招聘中
- Saint Bartholomew's Hospital
-
London、England、英国、W6 8RF
- 招聘中
- Charing Cross Hospital
-
接触:
- Charles P. Lowdell, MD, BSc, MBBS, FRCP, FRCR
- 电话号码:44-208-383-0576
- 邮箱:charles.lowdell@imperial.nhs.uk
-
London、England、英国、NW3 2PF
- 招聘中
- UCL Cancer Institute
-
接触:
- Astrid Mayer, MD
- 电话号码:44-207-794-0500
- 邮箱:a.mayer@ucl.ac.uk
-
Merseyside、England、英国、CH63 4JY
- 招聘中
- Clatterbridge Centre for Oncology
-
Newport、England、英国、PO30 5TG
- 招聘中
- St. Mary's Hospital
-
接触:
- Christopher Baughan, MD
- 电话号码:44-1983-524-081
-
Nottingham、England、英国、NG5 1PB
- 招聘中
- Cancer Research Centre at Weston Park Hospital
-
接触:
- J. Hornbuckle, MD
- 电话号码:44-115-969-1169 ext. 47599
-
Poole Dorset、England、英国、BH15 2JB
- 招聘中
- Dorset Cancer Centre
-
接触:
- Tamas Hickish, MD
- 电话号码:44-1202-442-532
-
Salisbury、England、英国、SP2 8BJ
- 招聘中
- Salisbury District Hospital
-
Southampton、England、英国、SO16 6YD
- 招聘中
- Southampton General Hospital
-
接触:
- John N. Primrose, MD
- 电话号码:44-23-8079-6144
- 邮箱:j.n.primrose@soton.ac.uk
-
Sutton、England、英国、SM2 5PT
- 招聘中
- Royal Marsden - Surrey
-
Westcliff-On-Sea、England、英国、SS0 0RY
- 招聘中
- Southend University Hospital NHS Foundation Trust
-
接触:
- Pauline Leonard, MD
- 电话号码:44-1702-435-555
-
Worthing、England、英国、BN11 2DH
- 招聘中
- Worthing Hospital
-
接触:
- Andrew Webb, MD
- 电话号码:44-1903-205-111
-
-
Wales
-
Cardiff、Wales、英国、CF14 2TL
- 招聘中
- Velindre Cancer Center at Velindre Hospital
-
接触:
- Timothy Maughan, MD
- 电话号码:44-2920-316-904
-
Cardiff、Wales、英国、CF14 4XW
- 招聘中
- University Hospital of Wales
-
接触:
- Timothy Maughan, MD
- 电话号码:44-2920-316-904
-
-
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
DISEASE CHARACTERISTICS:
Histologically* or radiologically confirmed primary adenocarcinoma of the colon or rectum
- Advanced and/or metastatic disease NOTE: *Liver metastases should not be biopsied
Must have potentially resectable liver metastases present, as defined by any of the following:
- Metachronous metastases AND complete resection of the primary tumor without gross or microscopic evidence of residual disease (R0)
- Synchronous metastases AND R0 resection of the primary tumor > 1 month before study entry
- Synchronous metastases with sufficient evidence (e.g., by CT scan or diagnostic laparoscopy) that both the primary tumor and the liver metastases can be completely resected during the same procedure and resection of primary tumor can be delayed for 3-4 months
- Suboptimally resectable disease (i.e., potentially resectable disease with compromise of the resection margins)
- No detectable extrahepatic tumor that cannot be completely resected
- Unidimensionally measurable disease
- No brain metastases
PATIENT CHARACTERISTICS:
- WHO performance status 0-2
- WBC ≥ 4,000/mm³
- ANC ≥ 1,500/mm³
- Platelet count > 150,000/mm³
- Bilirubin ≤ 1.25 times upper limit of normal (ULN)
- Alkaline phosphatase ≤ 5 times ULN
- AST or ALT ≤ 3 times ULN
- Creatinine clearance > 50 mL/min OR glomerular filtration rate > 50 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment
- No psychiatric or neurological condition that would preclude study compliance
- No partial or complete bowel obstruction
- No preexisting neuropathy > grade 1
- No other prior or concurrent malignant disease that, in the opinion of the investigator, would preclude study treatment
- No concurrent severe uncontrolled medical illness (including poorly-controlled angina or myocardial infarction within the past 3 months) that would preclude study treatment
- No known hypersensitivity reaction to any of the components of the study drugs
PRIOR CONCURRENT THERAPY:
- No prior systemic chemotherapy for metastatic disease
- More than 6 months since prior adjuvant chemotherapy comprising fluorouracil, leucovorin calcium, capecitabine, or irinotecan hydrochloride
- More than 1 month since prior rectal chemoradiotherapy comprising fluorouracil and leucovorin calcium
- No concurrent contraindicated medication
学习计划
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 |
---|---|
有源比较器:OxMdG / IrMdG chemotherapy
OxMdG / IrMdG chemotherapy for 12 weeks Followed by surgery OxMdG / IrMdG chemotherapy for 12 weeks
|
|
实验性的:OxMdG / IrMdG chemotherapy with cetuximab
OxMdG / IrMdG chemotherapy with cetuximab for 12 weeks Followed by Surgery OxMdG / IrMdG chemotherapy with cetuximab for 12 weeks
|
研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
---|---|
Progression-free survival
大体时间:end of study
|
end of study
|
次要结果测量
结果测量 |
大体时间 |
---|---|
总生存期
大体时间:研究结束
|
研究结束
|
Response rate before surgery as assessed by RECIST criteria
大体时间:end of study
|
end of study
|
Pathological resection status
大体时间:end of study
|
end of study
|
Toxicity
大体时间:end of study
|
end of study
|
Quality of life as assessed by the EQ-5D, EORTC QLQ-C30, and EORTC QLQ-LMC21
大体时间:end of study
|
end of study
|
Cost effectiveness
大体时间:end of study
|
end of study
|
Safety
大体时间:end of study
|
end of study
|
合作者和调查者
调查人员
- 学习椅:John N. Primrose, MD、University Hospital Southampton NHS Foundation Trust
研究记录日期
研究主要日期
学习开始
初级完成 (预期的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- CDR0000549541
- USCTU-4351
- USCTU-EPOC
- EUDRACT-2006-003121-82
- ISRCTN22944367
- EU-20732
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.