Inclusion criteria, exclusion criteria and study summary
The FOxTROT platform is a rolling programme of molecularly stratified, randomised phase II/III, multi-centre, international, open-label studies patients with locally advanced but operable colon cancer (CC). FOxTROT 2 is a phase III,multi-centre,open-label,international,randomised-controlled trial of modified dose of OxFp compared to STS,in patients unsuitable for FOLFOXIRI with a left-CC or with a right-CC tumour confirmed to be pMMR or MSS, and not felt to be at risk of bowel obstruction. FOxTROT 3 is a phase III, multi-centre, open-label, international, randomised-controlled trial of 6 weeks of NAC with OxFp then surgery compared to 6 weeks of NAC with mFOLFOXIRI then surgery, in younger and non-frail patients with a left-CC or with a right-CC tumour confirmed to be pMMR or MSS, and not felt to be at risk of bowel obstruction. Patients diagnosed with locally advanced but operable CC will be identified at a CC multidisciplinary team meeting following radiological assessment of the primary tumour and histological assessment of endoscopic biopsy. Potential participants will then be reviewed by a clinician and asked for consent to send their tumour block for biomarker testing (if MMR/MSI status is unknown) and translational research. The clinician will assess whether they are suitable to be treated on a neoadjuvant pathway and which comparison is most appropriate and provide the patient with a PIS. If MMR/MSI status is known at first assessment,or if patients have left primary tumour location (PTL),patients can proceed directly to assessment of suitability for each comparison and consent/ randomisation. Although MMR/MSI status is not a requirement for randomisation for patients with a left-PTL,testing is strongly recommended. If MMR/MSI status is being tested centrally,potential participants will be assessed for eligibility and suitability for each comparison once the results are available,and proceed to consent/randomisation.