On June 10, 2008, 1 week after announcement of the cetuximab data, a safety amendment was introduced to exclude patients with KRAS-mutated tumours from randomisation to the IrPan group; within 3 months PICCOLO was reopened as a prospectively stratified trial: patients with KRAS wild-type tumours were randomly allocated to irinotecan or IrPan while those with KRAS mutations (or unknown KRAS status) were randomly allocated to irinotecan or irinotecan plus ciclosporin. This evidence concerns the gene KRAS and neoplasm.