Combination Chemotherapy With or Without Cetuximab as First-Line Therapy in Treating Patients With Metastatic Colorectal Cancer
- Conditions
- Colorectal Cancer
- Registration Number
- NCT00182715
- Lead Sponsor
- Velindre NHS Trust
- Brief Summary
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. 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. It is not yet known whether combination chemotherapy and cetuximab are more effective than combination chemotherapy alone in treating colorectal cancer.
PURPOSE: This randomized phase III trial is studying combination chemotherapy and cetuximab to see how well they work compared to combination chemotherapy alone as first-line therapy in treating patients with metastatic colorectal cancer.
- Detailed Description
OBJECTIVES:
Primary
* Compare the overall survival of patients with metastatic colorectal adenocarcinoma treated with continuous combination chemotherapy comprising oxaliplatin, leucovorin calcium, and fluorouracil (OxMdG) or oxaliplatin and capecitabine (XELOX) with vs without cetuximab vs intermittent combination chemotherapy with OxMdG or XELOX as first-line therapy.
Secondary
* Compare time of disease control and progression- and failure-free survival of patients treated with these regimens.
* Compare response in patients treated with these regimens.
* Compare the toxicity of these regimens in these patients.
* Compare the cost effectiveness of these regimens in these patients.
* Compare the quality of life of patients treated with these regimens.
OUTLINE: This is a multicenter, open label, randomized, controlled study. Patients are randomized to 1 of 3 treatment arms.
* Arm I (continuous chemotherapy): Patients receive 1 of the following combination chemotherapy regimens of their choice (or as per participating center):
* OxMdG: Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46 hours on days 1 and 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
* XELOX: Patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
* Arm II (continuous chemotherapy and cetuximab): Patients receive OxMdG or XELOX as in arm I. Patients also receive cetuximab IV over 1-2 hours on days 1 and 8 (for patients receiving OxMdG) OR days 1, 8, and 15 (for patients receiving XELOX). Treatment with OxMdG and cetuximab repeats every 14 days in the absence of disease progression or unacceptable toxicity. Treatment with XELOX and cetuximab repeats every 21 days in the absence of disease progression or unacceptable toxicity.
* Arm III (intermittent chemotherapy): Patients receive OxMdG or XELOX as in arm I. Treatment with OxMdG repeats every 14 days for up to 6 courses (12 weeks). Treatment with XELOX repeats every 21 days for up to 4 courses (12 weeks). Patients with disease progression after 12 weeks of therapy are removed from study treatment. Patients with stable or responding disease after 12 weeks of therapy stop treatment and undergo clinical evaluation at least every 6 weeks (treatment break) until disease progression or clinical deterioration. Upon evidence of disease progression or clinical deterioration, patients restart treatment with OxMdG or XELOX as before and continue to alternate 12 weeks of treatment with treatment breaks in the absence of disease progression or unacceptable toxicity Quality of life is assessed at baseline, 6 weeks, 12 weeks, and then every 12 weeks thereafter.
After completion of study treatment, patients are followed every 12 weeks for survival.
Peer Reviewed and Funded or Endorsed by Cancer Research UK
PROJECTED ACCRUAL: A total of 2,421 patients (807 per treatment arm) will be accrued for this study within 3.5 years.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 2421
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Overall survival at 2 years
- Secondary Outcome Measures
Name Time Method Response by RECIST criteria at 12 and 24 weeks Toxicity by NCI Common Toxicity Criteria version 3 throughout treatment and at follow-up Time of disease control at 2 years Progression-free survival at 2 years Failure-free survival at 2 years
Trial Locations
- Locations (81)
Mater Misericordiae University Hospital
🇮🇪Dublin, Ireland
Mount Vernon Cancer Centre at Mount Vernon Hospital
🇬🇧Northwood, England, United Kingdom
University College of London Hospitals
🇬🇧London, England, United Kingdom
St. Luke's Cancer Centre at Royal Surrey County Hospital
🇬🇧Guildford, England, United Kingdom
Hinchingbrooke Hospital
🇬🇧Huntingdon, England, United Kingdom
Nottingham City Hospital NHS Trust
🇬🇧Nottingham, England, United Kingdom
Royal Preston Hospital
🇬🇧Preston, England, United Kingdom
Waterford Regional Hospital
🇮🇪Waterford, Ireland
Essex County Hospital
🇬🇧Colchester, England, United Kingdom
Derbyshire Royal Infirmary
🇬🇧Derby, England, United Kingdom
Huddersfield Royal Infirmary
🇬🇧Huddersfield, West Yorks, England, United Kingdom
Galway University Hospital
🇮🇪Galway, Ireland
Saint Bartholomew's Hospital
🇬🇧London, England, United Kingdom
St. George's Hospital
🇬🇧London, England, United Kingdom
North Hampshire Hospital
🇬🇧Basingstoke, England, United Kingdom
Eastbourne District General Hospital
🇬🇧Eastbourne, England, United Kingdom
Northampton General Hospital NHS Trust
🇬🇧Northampton, England, United Kingdom
Portsmouth Oncology Centre at Saint Mary's Hospital
🇬🇧Portsmouth Hants, England, United Kingdom
St. Vincent's University Hospital
🇮🇪Dublin, Ireland
Beaumont Hospital
🇮🇪Dublin, Ireland
Mid-Western Cancer Centre at Mid-Western Regional Hospital
🇮🇪Limerick, Ireland
Aintree University Hospital
🇬🇧Liverpool, England, United Kingdom
Royal Hampshire County Hospital
🇬🇧Winchester, England, United Kingdom
Helen Rollason Cancer Care Centre at North Middlesex Hospital
🇬🇧London, England, United Kingdom
St. Mary's Hospital
🇬🇧Newport, England, United Kingdom
Queen Elizabeth Hospital - Woolwich
🇬🇧London, England, United Kingdom
Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
🇬🇧Birmingham, England, United Kingdom
University Hospital of North Staffordshire
🇬🇧Stoke-On-Trent, England, United Kingdom
Good Hope Hospital Trust
🇬🇧West Midlands, England, United Kingdom
Royal Free and University College Medical School
🇬🇧London, England, United Kingdom
Cumberland Infirmary
🇬🇧Carlisle, England, United Kingdom
Peterborough Hospitals Trust
🇬🇧Peterborough, England, United Kingdom
Aberdeen Royal Infirmary
🇬🇧Aberdeen, Scotland, United Kingdom
Torbay Hospital
🇬🇧Torquay, England, United Kingdom
Scarborough General Hospital
🇬🇧Scarborough, England, United Kingdom
South Tyneside District Hospital
🇬🇧South Shields, England, United Kingdom
Royal Cornwall Hospital
🇬🇧Truro, Cornwall, England, United Kingdom
Hairmyres Hospital
🇬🇧East Kilbride, Scotland, United Kingdom
South West Wales Cancer Institute
🇬🇧Swansea, Wales, United Kingdom
Conquest Hospital
🇬🇧Saint Leonards-on-Sea, England, United Kingdom
Southampton General Hospital
🇬🇧Southampton, England, United Kingdom
Sunderland Royal Hospital
🇬🇧Sunderland, England, United Kingdom
Great Western Hospital
🇬🇧Swindon, England, United Kingdom
Walsall Manor Hospital
🇬🇧Walsall, England, United Kingdom
Belfast City Hospital Trust Incorporating Belvoir Park Hospital
🇬🇧Belfast, Northern Ireland, United Kingdom
Edinburgh Cancer Centre at Western General Hospital
🇬🇧Edinburgh, Scotland, United Kingdom
Royal Marsden - Surrey
🇬🇧Sutton, England, United Kingdom
Worcester Royal Hospital
🇬🇧Worcester, England, United Kingdom
Wrexham Maelor Hospital
🇬🇧Wrexham, Wales, United Kingdom
Worthing Hospital
🇬🇧Worthing, England, United Kingdom
Velindre Cancer Center at Velindre Hospital
🇬🇧Cardiff, Wales, United Kingdom
Adelaide and Meath Hospital, Dublin Incorporating the National Children's Hospital
🇮🇪Dublin, Ireland
Mercy University Hospital
🇮🇪Cork, Ireland
St. James's Hospital
🇮🇪Dublin, Ireland
Queen's Hospital
🇬🇧Burton-upon-Trent, England, United Kingdom
Royal Bournemouth Hospital NHS Trust
🇬🇧Bournemouth, England, United Kingdom
Royal Marsden - London
🇬🇧London, England, United Kingdom
Glan Clwyd Hospital
🇬🇧Rhyl, Denbighshire, Wales, United Kingdom
Bradford Royal Infirmary
🇬🇧Bradford, England, United Kingdom
Mater Private Hospital
🇮🇪Dublin, Ireland
Sussex Cancer Centre at Royal Sussex County Hospital
🇬🇧Brighton, England, United Kingdom
West Suffolk Hospital
🇬🇧Bury St. Edmunds, England, United Kingdom
Dorset County Hospital
🇬🇧Dorchester, England, United Kingdom
Princess Royal Hospital at Hull and East Yorkshire NHS Trust
🇬🇧Hull, England, United Kingdom
Southport and Formby District General Hospital
🇬🇧Merseyside, England, United Kingdom
North Tyneside Hospital
🇬🇧North Shields, England, United Kingdom
Poole Hospital NHS Trust
🇬🇧Poole Dorset, England, United Kingdom
Yeovil District Hospital
🇬🇧Yeovil, England, United Kingdom
Raigmore Hospital
🇬🇧Inverness, Scotland, United Kingdom
Hammersmith Hospital
🇬🇧London, England, United Kingdom
Cancer Research UK Clinical Groups at Guy's King's & St. Thomas' Hospitals
🇬🇧London, England, United Kingdom
Blackpool Victoria Hospital
🇬🇧Blackpool, England, United Kingdom
Bristol Haematology and Oncology Centre
🇬🇧Bristol, England, United Kingdom
Addenbrooke's Hospital
🇬🇧Cambridge, England, United Kingdom
Cheltenham General Hospital
🇬🇧Cheltenham, England, United Kingdom
Princess Alexandra Hospital
🇬🇧Essex, England, United Kingdom
Cookridge Hospital
🇬🇧Leeds, England, United Kingdom
Derriford Hospital
🇬🇧Plymouth, England, United Kingdom
Whiston Hospital
🇬🇧Prescot Merseyside, England, United Kingdom
Salisbury District Hospital
🇬🇧Salisbury, England, United Kingdom
Charing Cross Hospital
🇬🇧London, England, United Kingdom