Evaluation of RAS mutations in cell free deoxyribonucleic acid (cfDNA) in response to cetuximab anti-epidermal growth factor receptor (EGFR) therapy in patients with metastatic colorectal cancer.

This is a prospective multi-centre biomarker study involving the collection of plasma from patients with a Ras wild-type (according to the local standard of care) tumour planned for treatment with first-line cetuximab in combination with Irinotecan with fluorouracil (5FU) and folinic acid (FOLFIRI) or Oxaliplatin with fluorouracil (5FU) and folinic acid (FOLFOX) will be periodically assessed with the following minimum study procedures. Additional non-study assessments may occur at the discretion of the treating clinician. Blood sampling at the following time points: a) Baseline (within 7 days of starting anti-EGFR treatment) b) Week 3 of anti-EGFR treatment (after 2 weeks of treatment) c) Week 5 of anti-EGFR treatment (after 4 weeks of treatment) d) Every 4 weeks thereafter until disease progression Representative archival tumour sample (either primary or metastasis tissue) will be made available for next-generation sequencing (NGS) based Ras testing (unless already performed) and/or for repeat RAS mutation analysis by BEAMing (Beads, Emulsions, Amplification, and Magnetics) digital PCR (polymerase chain reaction) assay where there is any discordance between tumour tissue and cfDNA analysis. Images from the following staging CT chest/abdomen/pelvis performed as part of routine care will be centrally reviewed by a radiologist: a. Screening – within 4 weeks of starting anti-EGFR therapy b. Every 8 weeks until disease progression using CEA and imaging. Follow-up as per standard practice until disease progression, death or a maximum of 3 years, which ever occurs first.