NCT00389870

Irinotecan With or Without Panitumumab or Cyclosporine in Treating Patients With Advanced or Metastatic Colorectal Cancer That Did Not Respond to Fluorouracil

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)]

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1,198 (actual)
• Sponsor: University of Leeds · Academic / Other
• Sex: All
• Age: 18 Years – 120 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Colorectal Cancer

Interventions

Type	Name	Description
BIOLOGICAL	panitumumab
DRUG	cyclosporine
DRUG	irinotecan hydrochloride

Timeline

• Start date: 2006-12-01
• First posted: 2006-10-19
• Last updated: 2022-06-01

Locations

33 sites across 1 country: United Kingdom