Irinotecan With or Without Panitumumab or Cyclosporine in Treating Patients With Advanced or Metastatic Colorectal Cancer That Did Not Respond to Fluorouracil
Recruitment status was Recruiting
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.
Drug: irinotecan hydrochloride
|Study Design:||Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Randomised Clinical Trial of Treatment for Fluorouracil-Resistant Advanced Colorectal Cancer Comparing Standard Single-Agent Irinotecan Versus Irinotecan Plus Panitumumab and Versus Irinotecan Plus Ciclosporin [Panitumumab, Irinotecan & Ciclosporin in COLOrectal Cancer Therapy (PICCOLO)]|
- Proportion of patients treated with irinotecan hydrochloride (Ir) alone vs Ir and cyclosporine (IrC) who are progression-free at 12 weeks [ Designated as safety issue: No ]
- Overall survival of patients treated with Ir vs Ir and panitumumab (IrP) and no prior cetuximab [ Designated as safety issue: No ]
- Proportion of patients free from treatment failure at 12 weeks in patients treated with Ir vs IrC [ Designated as safety issue: No ]
- Overall survival in patients treated with Ir vs IrC [ Designated as safety issue: No ]
- Nurse-assessed toxicity (all-cause mortality, diarrhea ≥ grade 3 at 12 weeks) in patients treated with Ir vs IrC [ Designated as safety issue: Yes ]
- Progression-free at 12 weeks in patients treated with Ir vs IrP and no prior cetuximab [ Designated as safety issue: No ]
- Nurse assessed toxicity (all-cause mortality) in patients treated with Ir vs IrP and no prior cetuximab [ Designated as safety issue: Yes ]
- Progression-free survival in patients treated with Ir vs IrP and prior cetuximab [ Designated as safety issue: No ]
- Best response at 1 year in patients treated with Ir vs IrP and prior cetuximab [ Designated as safety issue: No ]
- Patient-assessed symptom/quality of life/acceptability scores at 12 and 24 weeks in patients treated with Ir vs IrP and prior cetuximab [ Designated as safety issue: No ]
|Study Start Date:||December 2006|
|Estimated Primary Completion Date:||March 2010 (Final data collection date for primary outcome measure)|
- 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.
- 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.
|Royal Bournemouth Hospital NHS Trust||Recruiting|
|Bournemouth, England, United Kingdom, BH7 7DW|
|Contact: Tamas Hickish, MD 44-120-230-3626 firstname.lastname@example.org|
|Sussex Cancer Centre at Royal Sussex County Hospital||Recruiting|
|Brighton, England, United Kingdom, BN2 5BE|
|Contact: Andrew Webb, MD 44-12-7369-6955|
|Bristol Haematology and Oncology Centre||Recruiting|
|Bristol, England, United Kingdom, BS2 8ED|
|Contact: Stephen J. Falk, MD 44-117-928-2416 email@example.com|
|Cambridge, England, United Kingdom, CB2 2QQ|
|Contact: Charles B. Wilson, MD 44-1223-217-110 firstname.lastname@example.org|
|Gloucestershire Oncology Centre at Cheltenham General Hospital||Recruiting|
|Cheltenham, England, United Kingdom, GL53 7AN|
|Contact: Kim Benstead, MD 44-845-422-2222 email@example.com|
|Eastbourne District General Hospital||Recruiting|
|Eastbourne, England, United Kingdom, BN21 2UD|
|Contact: Fiona McKinna, MD 44-132-341-7400 firstname.lastname@example.org|
|St. Luke's Cancer Centre at Royal Surrey County Hospital||Recruiting|
|Guildford, England, United Kingdom, GU2 7XX|
|Contact: Gary W. Middleton 44-148-357-1122 email@example.com|
|Huddersfield Royal Infirmary||Recruiting|
|Huddersfield, West Yorks, England, United Kingdom, HD3 3EA|
|Contact: Jo Dent 44-1484-342-000|
|Huntingdon, England, United Kingdom, PE18 6NT|
|Contact: Li Tee Tan, MD 44-1480-416-416|
|Airedale General Hospital||Recruiting|
|Keighley, England, United Kingdom, BD20 6TD|
|Contact: S. Michael Crawford, MD 44-1535-652-511 firstname.lastname@example.org|
|Leeds, England, United Kingdom, LS16 6QB|
|Contact: Matthew T. Seymour, MA, MD, FRCP 44-113-267-3411|
|Royal Liverpool University Hospital||Recruiting|
|Liverpool, England, United Kingdom, L7 8XP|
|Contact: David Smith, MD 44-151-706-2000|
|St. Mary's Hospital||Recruiting|
|London, England, United Kingdom, W2 1NY|
|Contact: Susan Cleator, MD, PhD 44-207-886-6666 email@example.com|
|Queen Elizabeth Hospital - Woolwich||Recruiting|
|London, England, United Kingdom, SE18 4QH|
|Contact: Nick Maisey 44-208-836-6000 firstname.lastname@example.org|
|UCL Cancer Institute||Recruiting|
|London, England, United Kingdom, NW3 2PF|
|Contact: Astrid Mayer, MD 44-207-794-0500 email@example.com|
|Mid Kent Oncology Centre at Maidstone Hospital||Recruiting|
|Maidstone, England, United Kingdom, ME16 9QQ|
|Contact: Mark Hill, MD 44-1622-729-000|
|Clatterbridge Centre for Oncology||Recruiting|
|Merseyside, England, United Kingdom, CH63 4JY|
|Contact: Sun Myint, MD, FRCP(Edin), DMRT, FFRCS, F 44-151-334-1155 firstname.lastname@example.org|
|James Cook University Hospital||Recruiting|
|Middlesbrough, England, United Kingdom, TS4 3BW|
|Contact: N. Wadd, MD 44-1642-850-850|
|Mount Vernon Cancer Centre at Mount Vernon Hospital||Recruiting|
|Northwood, England, United Kingdom, HA6 2RN|
|Contact: Robert Glynne-Jones, MD 44-192-382-6111 email@example.com|
|Peterborough Hospitals Trust||Recruiting|
|Peterborough, England, United Kingdom, PE3 6DA|
|Contact: Karen E. McAdam, MD 44-173-387-4000|
|Dorset Cancer Centre||Recruiting|
|Poole Dorset, England, United Kingdom, BH15 2JB|
|Contact: Tamas Hickish, MD 44-120-266-5511|
|Portsmouth Oncology Centre at Saint Mary's Hospital||Recruiting|
|Portsmouth Hants, England, United Kingdom, PO3 6AD|
|Contact: Ann O'Callaghan, MD 44-23-9228-6000 ext. 2361 firstname.lastname@example.org|
|Cancer Research Centre at Weston Park Hospital||Recruiting|
|Sheffield, England, United Kingdom, S1O 2SJ|
|Contact: Jonathan Wadsley 44-114-226-5000|
|South Tyneside District Hospital||Recruiting|
|South Shields, England, United Kingdom, NE34 0PL|
|Contact: Ashraf Azzabi, MD 44-191-202-4178|
|Royal Marsden - Surrey||Recruiting|
|Sutton, England, United Kingdom, SM2 5PT|
|Contact: Ian Chau, MD 44-208-661-3582|
|Great Western Hospital||Recruiting|
|Swindon, England, United Kingdom, SN3 6BB|
|Contact: Claire Blesing 44-1793-604-020|
|Worthing, England, United Kingdom, BN11 2DH|
|Contact: Andrew Webb, MD 44-1903-205-111|
|Yeovil District Hospital||Recruiting|
|Yeovil, England, United Kingdom, BA21 4AT|
|Contact: Stephen J. Falk, MD 44-193-547-5122 email@example.com|
|Edinburgh Cancer Centre at Western General Hospital||Recruiting|
|Edinburgh, Scotland, United Kingdom, EH4 2XU|
|Contact: Lesley Dawson 44-131-537-1000|
|Bangor, Wales, United Kingdom, LL57 2PW|
|Contact: Catherine Bale 44-124-838-4384|
|Velindre Cancer Center at Velindre Hospital||Recruiting|
|Cardiff, Wales, United Kingdom, CF14 2TL|
|Contact: Timothy Maughan, MD 44-29-2061-5888|
|Glan Clwyd Hospital||Recruiting|
|Rhyl, Denbighshire, Wales, United Kingdom, LL 18 5UJ|
|Contact: Simon Gollins, MD 44-1745-583-910 firstname.lastname@example.org|
|South West Wales Cancer Institute||Recruiting|
|Swansea, Wales, United Kingdom, SA2 8QA|
|Contact: John Wagstaff, MD, MB, ChB, FRCP 44-179-220-2666 email@example.com|
|Study Chair:||Matthew T. Seymour, MA, MD, FRCP||Cookridge Hospital|