Irinotecan With or Without Panitumumab or Cyclosporine in Treating Patients With Advanced or Metastatic Colorectal Cancer That Did Not Respond to Fluorouracil
- Conditions
- Colorectal Cancer
- Registration Number
- NCT00389870
- Lead Sponsor
- University of Leeds
- Brief Summary
RATIONALE: Drugs used in chemotherapy, such as irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cyclosporine may help irinotecan work better by making tumor cells more sensitive to the drug. Monoclonal antibodies, such as panitumumab, 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. Panitumumab may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether irinotecan is more effective when given with or without panitumumab or cyclosporine in treating colorectal cancer.
PURPOSE: This randomized phase III trial is studying irinotecan to compare how well it works when given with or without panitumumab or cyclosporine in treating patients with advanced or metastatic colorectal cancer that did not respond to fluorouracil.
- Detailed Description
OBJECTIVES:
Primary
* Compare the efficacy and toxicity of single-agent irinotecan hydrochloride (Ir) vs Ir with cyclosporine (IrC) in patients with fluorouracil-resistant advanced colorectal cancer.
* Compare the efficacy of single-agent Ir vs Ir with panitumumab (IrP) in these patients.
Secondary
* Correlate the toxicity of Ir and/or IrC with genetic variability in the enzymes involved in irinotecan hydrochloride's disposition pathway.
* Compare IrC to Ir and its metabolites (SN38; SN38G), in terms of pharmacokinetic profile.
* Correlate the benefit of IrP with tumor expression of epidermal growth factor receptor (EGFR) or its known down-stream molecules as a predictive measure.
* Correlate IrP efficacy or toxicity (specifically the severity of skin rash) with somatic alterations in the EGFR gene and/or with germline variability in related genes.
OUTLINE: This is a randomized, open-label, controlled, multicenter study. Patients are stratified according to prior cetuximab (yes vs no). Patients are randomized to 1 of 3 treatment arms.
* Arm I: Patients receive irinotecan hydrochloride IV over 30-90 minutes on day 1.
* Arm II: Patients receive irinotecan hydrochloride IV over 15-40 minutes on day 1 and oral cyclosporine three times a day on days 1-3.
* Arm III: Patients receive panitumumab IV over 30-90 minutes followed by irinotecan hydrochloride IV over 30-90 minutes on day 1. Single-agent panitumumab may be continued during breaks in chemotherapy treatment.
In all arms, treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with responding or stable disease may continue treatment in the absence of disease progression or unacceptable toxicity.
Quality of life is assessed at baseline and at 12 and 24 weeks.
After completion of study treatment, patients are followed every 12 weeks for 1 year.
Peer Reviewed and Funded or Endorsed by Cancer Research UK
PROJECTED ACCRUAL: A total of 1,269 patients will be accrued for this study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1198
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Proportion of patients treated with irinotecan hydrochloride (Ir) alone vs Ir and cyclosporine (IrC) who are progression-free at 12 weeks Overall survival of patients treated with Ir vs Ir and panitumumab (IrP) and no prior cetuximab
- Secondary Outcome Measures
Name Time Method Progression-free survival in patients treated with Ir vs IrP and prior cetuximab Proportion of patients free from treatment failure at 12 weeks in patients treated with Ir vs IrC Overall survival in patients treated with Ir vs IrC Nurse-assessed toxicity (all-cause mortality, diarrhea ≥ grade 3 at 12 weeks) in patients treated with Ir vs IrC Progression-free at 12 weeks in patients treated with Ir vs IrP and no prior cetuximab Nurse assessed toxicity (all-cause mortality) in patients treated with Ir vs IrP and no prior cetuximab Best response at 1 year in patients treated with Ir vs IrP and prior cetuximab Patient-assessed symptom/quality of life/acceptability scores at 12 and 24 weeks in patients treated with Ir vs IrP and prior cetuximab
Trial Locations
- Locations (33)
James Cook University Hospital
🇬🇧Middlesbrough, England, United Kingdom
Royal Marsden - Surrey
🇬🇧Sutton, England, United Kingdom
Clatterbridge Centre for Oncology
🇬🇧Merseyside, England, United Kingdom
Gloucestershire Oncology Centre at Cheltenham General Hospital
🇬🇧Cheltenham, England, United Kingdom
Cookridge Hospital
🇬🇧Leeds, England, United Kingdom
Queen Elizabeth Hospital - Woolwich
🇬🇧London, England, United Kingdom
Dorset Cancer Centre
🇬🇧Poole Dorset, England, United Kingdom
St. Mary's Hospital
🇬🇧London, England, United Kingdom
South Tyneside District Hospital
🇬🇧South Shields, England, United Kingdom
Yeovil District Hospital
🇬🇧Yeovil, England, United Kingdom
Cancer Research Centre at Weston Park Hospital
🇬🇧Sheffield, England, United Kingdom
Edinburgh Cancer Centre at Western General Hospital
🇬🇧Edinburgh, Scotland, United Kingdom
Mount Vernon Cancer Centre at Mount Vernon Hospital
🇬🇧Northwood, England, United Kingdom
Portsmouth Oncology Centre at Saint Mary's Hospital
🇬🇧Portsmouth Hants, England, United Kingdom
South West Wales Cancer Institute
🇬🇧Swansea, Wales, United Kingdom
Glan Clwyd Hospital
🇬🇧Rhyl, Denbighshire, Wales, United Kingdom
Royal Bournemouth Hospital
🇬🇧Bournemouth, England, United Kingdom
Addenbrooke's Hospital
🇬🇧Cambridge, England, United Kingdom
Sussex Cancer Centre at Royal Sussex County Hospital
🇬🇧Brighton, England, United Kingdom
Eastbourne District General Hospital
🇬🇧Eastbourne, England, United Kingdom
St. Luke's Cancer Centre at Royal Surrey County Hospital
🇬🇧Guildford, England, United Kingdom
Huddersfield Royal Infirmary
🇬🇧Huddersfield, West Yorks, England, United Kingdom
Hinchingbrooke Hospital
🇬🇧Huntingdon, England, United Kingdom
Airedale General Hospital
🇬🇧Keighley, England, United Kingdom
UCL Cancer Institute
🇬🇧London, England, United Kingdom
Peterborough Hospitals Trust
🇬🇧Peterborough, England, United Kingdom
Great Western Hospital
🇬🇧Swindon, England, United Kingdom
Worthing Hospital
🇬🇧Worthing, England, United Kingdom
Velindre Cancer Center at Velindre Hospital
🇬🇧Cardiff, Wales, United Kingdom
Ysbyty Gwynedd
🇬🇧Bangor, Wales, United Kingdom
Bristol Haematology and Oncology Centre
🇬🇧Bristol, England, United Kingdom
Mid Kent Oncology Centre at Maidstone Hospital
🇬🇧Maidstone, England, United Kingdom
Royal Liverpool University Hospital
🇬🇧Liverpool, England, United Kingdom