Combination Chemotherapy With or Without Cetuximab Before and After Surgery in Treating Patients With Resectable Liver Metastases Caused By Colorectal Cancer
- Conditions
- Colorectal CancerMetastatic Cancer
- Interventions
- Biological: cetuximabOther: study of socioeconomic and demographic variablesProcedure: adjuvant therapyProcedure: neoadjuvant therapyProcedure: quality-of-life assessment
- Registration Number
- NCT00482222
- Lead Sponsor
- University of Southampton
- Brief Summary
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.
- Detailed Description
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
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 340
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description OxMdG / IrMdG chemotherapy leucovorin calcium OxMdG / IrMdG chemotherapy for 12 weeks Followed by surgery OxMdG / IrMdG chemotherapy for 12 weeks OxMdG / IrMdG chemotherapy adjuvant therapy OxMdG / IrMdG chemotherapy for 12 weeks Followed by surgery OxMdG / IrMdG chemotherapy for 12 weeks OxMdG / IrMdG chemotherapy with cetuximab adjuvant therapy OxMdG / IrMdG chemotherapy with cetuximab for 12 weeks Followed by Surgery OxMdG / IrMdG chemotherapy with cetuximab for 12 weeks OxMdG / IrMdG chemotherapy neoadjuvant therapy OxMdG / IrMdG chemotherapy for 12 weeks Followed by surgery OxMdG / IrMdG chemotherapy for 12 weeks OxMdG / IrMdG chemotherapy quality-of-life assessment OxMdG / IrMdG chemotherapy for 12 weeks Followed by surgery OxMdG / IrMdG chemotherapy for 12 weeks OxMdG / IrMdG chemotherapy study of socioeconomic and demographic variables OxMdG / IrMdG chemotherapy for 12 weeks Followed by surgery OxMdG / IrMdG chemotherapy for 12 weeks OxMdG / IrMdG chemotherapy with cetuximab study of socioeconomic and demographic variables OxMdG / IrMdG chemotherapy with cetuximab for 12 weeks Followed by Surgery OxMdG / IrMdG chemotherapy with cetuximab for 12 weeks OxMdG / IrMdG chemotherapy with cetuximab quality-of-life assessment OxMdG / IrMdG chemotherapy with cetuximab for 12 weeks Followed by Surgery OxMdG / IrMdG chemotherapy with cetuximab for 12 weeks OxMdG / IrMdG chemotherapy with cetuximab cetuximab OxMdG / IrMdG chemotherapy with cetuximab for 12 weeks Followed by Surgery OxMdG / IrMdG chemotherapy with cetuximab for 12 weeks OxMdG / IrMdG chemotherapy with cetuximab leucovorin calcium OxMdG / IrMdG chemotherapy with cetuximab for 12 weeks Followed by Surgery OxMdG / IrMdG chemotherapy with cetuximab for 12 weeks OxMdG / IrMdG chemotherapy with cetuximab neoadjuvant therapy OxMdG / IrMdG chemotherapy with cetuximab for 12 weeks Followed by Surgery OxMdG / IrMdG chemotherapy with cetuximab for 12 weeks OxMdG / IrMdG chemotherapy fluorouracil OxMdG / IrMdG chemotherapy for 12 weeks Followed by surgery OxMdG / IrMdG chemotherapy for 12 weeks OxMdG / IrMdG chemotherapy capecitabine OxMdG / IrMdG chemotherapy for 12 weeks Followed by surgery OxMdG / IrMdG chemotherapy for 12 weeks OxMdG / IrMdG chemotherapy oxaliplatin OxMdG / IrMdG chemotherapy for 12 weeks Followed by surgery OxMdG / IrMdG chemotherapy for 12 weeks OxMdG / IrMdG chemotherapy with cetuximab fluorouracil OxMdG / IrMdG chemotherapy with cetuximab for 12 weeks Followed by Surgery OxMdG / IrMdG chemotherapy with cetuximab for 12 weeks OxMdG / IrMdG chemotherapy with cetuximab capecitabine OxMdG / IrMdG chemotherapy with cetuximab for 12 weeks Followed by Surgery OxMdG / IrMdG chemotherapy with cetuximab for 12 weeks OxMdG / IrMdG chemotherapy with cetuximab oxaliplatin OxMdG / IrMdG chemotherapy with cetuximab for 12 weeks Followed by Surgery OxMdG / IrMdG chemotherapy with cetuximab for 12 weeks
- Primary Outcome Measures
Name Time Method Progression-free survival end of study
- Secondary Outcome Measures
Name Time Method Toxicity end of study Response rate before surgery as assessed by RECIST criteria end of study Pathological resection status end of study Overall survival end of study Quality of life as assessed by the EQ-5D, EORTC QLQ-C30, and EORTC QLQ-LMC21 end of study Safety end of study Cost effectiveness end of study
Trial Locations
- Locations (22)
Addenbrooke's Hospital
🇬🇧Cambridge, England, United Kingdom
St. Mary's Hospital
🇬🇧Newport, England, United Kingdom
Royal Marsden - London
🇬🇧London, England, United Kingdom
Charing Cross Hospital
🇬🇧London, England, United Kingdom
Royal Bournemouth Hospital
🇬🇧Bournemouth, England, United Kingdom
Salisbury District Hospital
🇬🇧Salisbury, England, United Kingdom
Saint Bartholomew's Hospital
🇬🇧London, England, United Kingdom
Basildon University Hospital
🇬🇧Basildon, England, United Kingdom
Basingstoke and North Hampshire NHS Foundation Trust
🇬🇧Basingstoke, England, United Kingdom
UCL Cancer Institute
🇬🇧London, England, United Kingdom
St. Luke's Cancer Centre at Royal Surrey County Hospital
🇬🇧Guildford, England, United Kingdom
Aintree University Hospital
🇬🇧Liverpool, England, United Kingdom
Clatterbridge Centre for Oncology
🇬🇧Merseyside, England, United Kingdom
Dorset Cancer Centre
🇬🇧Poole Dorset, England, United Kingdom
Cancer Research Centre at Weston Park Hospital
🇬🇧Nottingham, England, United Kingdom
Southampton General Hospital
🇬🇧Southampton, England, United Kingdom
Royal Marsden - Surrey
🇬🇧Sutton, England, United Kingdom
Southend University Hospital NHS Foundation Trust
🇬🇧Westcliff-On-Sea, England, United Kingdom
Worthing Hospital
🇬🇧Worthing, England, United Kingdom
Velindre Cancer Center at Velindre Hospital
🇬🇧Cardiff, Wales, United Kingdom
University Hospital of Wales
🇬🇧Cardiff, Wales, United Kingdom
Royal Liverpool University Hospital
🇬🇧Liverpool, England, United Kingdom