Irinotecan With or Without Panitumumab or Cyclosporine in Treating Patients With Advanced or Metastatic Colorectal Cancer That Did Not Respond to Fluorouracil
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): panitumumab; cyclosporine; irinotecan hydrochloride
Intervention type(s): Biological; Drug; Drug
Intervention MeSH terms: Cyclosporine; Irinotecan; Panitumumab; Cyclosporins
Allocation: Randomized
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: recurrent colon cancer; stage IV colon cancer; recurrent rectal cancer; stage IV rectal cancer; adenocarcinoma of the colon; adenocarcinoma of the rectum