ICECREAM: Irinotecan Cetuximab Evaluation and the Cetuximab Response Evaluation Among Patients with G13D Mutation (#328)
Background: Patients with metastatic colorectal cancer (mCRC) with disease that has progressed despite oxaliplatin and irinotecan containing regimens may benefit from the use of EGFR-inhibiting monoclonal antibodies if the tumour contains no mutations in the KRAS gene (i.e. WT).
However, it is unknown whether antibodies used in this setting, such as cetuximab, are more efficacious alone or in combination with irinotecan, as suggested by the BOND study which did not select for KRAS status.
This Australian-led international trial will also evaluate prospectively the activity of cetuximab in the subgroup of patients with mCRC with a specific KRAS mutation in codon G13D. In selected retrospective analyses, tumours bearing this mutation appear to derive similar response from cetuximab as WT. Trials involving small molecular subsets (in this case approx. 5% of patients with mCRC, or 18% of patients with KRAS mutations) will provide framework for future collaborations.
Methods: Randomised phase II study of cetuximab +/- irinotecan of patients with metastatic colorectal cancer (mCRC) with either KRAS WT (n=50) or G13D mutation (n=50) over 2 years from sites in Australia (12), and three international sites (G13D mutations only): Spain (1), England (1), and Italy (1). The trial will prospectively select the KRAS WT arm for the “quadruple WT" genotype (no mutations also in BRAF, NRAS, PIK3CA exon20).
Eligibility: Patients with histologically confirmed CRC with either “quadruple WT" genotype or KRAS G13D mutation; unresectable metastatic disease; measurable or evaluable disease; ECOG 0-1; life expectancy at least 12 weeks, and disease progression, or intolerance of thymidylate synthase inhibitor and irinotecan and oxaliplatin containing regimens.
Primary objective is 6 month progression free survival. Secondary objectives are response rate, overall survival, quality of life, and translational research including markers that may predict response.
Status: Opened to accrual November 2012, at 8 August 2013 23/100 patients have been enrolled.