Anti-EGFR Agents in Patients With Right-sided Advanced Colorectal Cancer With Wild-type RAS and AREG/EREG High Status

ARIEL-ENGIC is a multi-centre, phase IV, open label, randomised controlled biomarker enrichment trial with an internal pilot phase in which participants with wild-type RAS, right-PTL and EREG/AREG high aCRC will be randomized in a 1:1 ratio to receive chemotherapy (doublet) plus cetuximab versus chemotherapy (doublet or triplet) alone or with bevacizumab. ARIEL-ENGIC is an international trial in which the UK (recruitment ongoing) and EU (Italy, Germany and Spain) are participating. ARIEL-ENGIC aims to randomize 280 participants at a global level. In Europe 60 centers will be involved and 120 participants (40 pts per Member State involved) will be randomized. Given the biomarker prevalence, 660 participants will be registered to identify sufficient RAS-wt participants with high tumour EREG/AREG expression. The ARIEL-ENGIC study has 2 phases, registration and randomization (the main trial). Participants meeting all of the inclusion criteria and none of the exclusion criteria for registration will be considered for trial eligibility and biomarker analysis. Tumour samples will be sent for centralized biomarker (EREG/AREG) assessment. Participants with high tumour EREG/AREG will be eligible for randomisation. Participants eligible for the randomisation phase will be allocated 1:1 to chemotherapy alone or with bevacizumab or chemotherapy plus anti-EGFR agent. Stratification factors will be: * Choice of first-line chemotherapy (irinotecan-based doublet; oxaliplatin-based doublet; FOLFOXIRI) * Tumour location (transverse vs caecum vs ascending) * Prior adjuvant or neoadjuvant chemotherapy (yes vs no) * Primary tumour resected * Country of registration