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)]
- Compare the efficacy and toxicity of single-agent irinotecan hydrochloride (Ir) vs Ir
with cyclosporine (IrC) in patients with fluorouracil-resistant advanced colorectal
- 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
- 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
- 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.
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Proportion of patients treated with irinotecan hydrochloride (Ir) alone vs Ir and cyclosporine (IrC) who are progression-free at 12 weeks
Matthew T. Seymour, MA, MD, FRCP