FOxTROT: Personalising neo-adjuvant Chemotherapy in Locally advanced but operable colon cancer. A randomised trial programme.

Study ID: 49772
Short Title: FOxTROT Platform
Trust Name: DCHFT,UHD
Recruitment Site: Dorset County Hospital,Poole Hospital,Royal Bournemouth Hospital
Disease Area: Colorectal cancer
Phase: III
Expected End Date: 01/08/2026
Postcode: DT1 2JY
BH15 2JB
Contact Name: Amanda Pattie
Contact Email: studysupport1and3.crnwessex@nihr.ac.uk
Active: Yes

Inclusion criteria, exclusion criteria and study summary

Patients will have met the following FOxTROT Registration inclusion criteria: • Biopsy-confirmed adenocarcinoma of the colon (or upper rectum if too high for radiotherapy); high grade dysplasia is acceptable with unequivocal radiological evidence of invasive cancer* • Radiological stage T3-4, N0-2, M0 • Patient being treated with curative intent • Tumour tissue is available for molecular testing (local or central) • Age ≥18 at the time of registration • Patient able and willing to provide written informed consent for the study * Patients with synchronous tumours are eligible, if the most advanced tumour meets the criteria above (please note molecular testing will be of the most advanced tumour) For FoxTROT 2, patients will also have met the following protocol-specific criteria: • Patients will be unsuitable for mFOLFOXIRI due to oncologist assessed frailty or comorbidity • pMMR/MSS tumour status (for right sided tumours) • CC specialist-assessed fit to receive 6 weeks of NAC with OxFp (either full or modified dose) and surgery. • Adequate full blood count: WBC > 3.0 x10^9/l; Plts > 100 x10^9/l; neutrophils ≥1.5 x10^9/l. Anaemia (Hb < 10.0 g/dl) is not an exclusion, but should be corrected by transfusion prior to surgery and chemotherapy. If Hb remains low despite transfusions, surgery and chemotherapy can be given at the decision of the surgical and oncology teams. • Adequate renal biochemistry: GFR > 50 ml/min as assessed by local standards • Adequate hepatobiliary function: bilirubin < 1.5 ULN (Patients with Gilbert’s syndrome who have raised bilirubin but otherwise normal liver function tests are eligible for the study.) AST/ALT < 2.5 x ULN. • If female and of childbearing potential, must agree to avoid pregnancy during and for 6 months after last dose of study treatment • If male with a partner of childbearing potential, must: - Agree to use adequate, medically approved, contraceptive precautions during and for 6 months after the last dose of study treatment • Signed the Informed Consent Document for randomisation For FoxTROT 3, patients will also have met the following protocol-specific criteria: • Patients need to be fit and suitable for mFOLFOXIRI. There is no fixed age cut-off, but most patients will be under 70 years. • pMMR/MSS tumour status (for right sided tumours) • Adequate full blood count: WBC > 3.0 x10^9/l; Neutrophils ≥1.5 x10^9/l Plts > 100 x10^9/l. Anaemia (Hb < 100 g/l) is not an exclusion but should be corrected by transfusion prior to surgery and chemotherapy. If Hb remains low despite transfusions, surgery and chemotherapy can be given at the decision of the surgical and oncology teams. • Adequate renal biochemistry: GFR > 50 ml/min as assessed by local standards • Adequate hepatobiliary function: bilirubin < 1.5 x ULN (Patients with Gilbert’s syndrome who have raised bilirubin but otherwise normal liver function tests are eligible for the study.) AST/ALT < 2.5 x ULN. • If female and of childbearing potential, must agree to avoid pregnancy during and for 6 months after the last dose of study treatment • If male with a partner of childbearing potential, must: - Agree to use adequate, medically approved, contraceptive precautions during and for 6 months after the last dose of study treatment • Signed the Informed Consent Document for randomisation

Patients will not have any of the following (as per FOxTROT Registration exclusion criteria): • Any patient for whom radiotherapy is advised by the MDT • Cases with a high index of suspicion of distant metastases or peritoneal nodules (cM1). However, cases with indeterminate abnormalities should be managed and investigated as per standard local MDT procedures and can be considered for trial entry if the MDT opinion is that these are considered most likely to be benign. • Colonic obstruction that has not been defunctioned* • Women who are pregnant or breastfeeding * Patients with symptomatic bowel obstruction cannot be included in the Foxtrot trial platform, unless the obstruction has been relieved. This would usually be by defunctioning. Patients may also be stented, but there is more limited safety data on this and these cases should be individually discussed with the TMG. For FOxTROT 2, additionally patients will not have met any of the following protocol-specific exclusion criteria: • Serious medical comorbidity,as assessed by leading clinician (such as uncontrolled angina) • Any other malignant disease within the preceding 5 years with the exception of non-melanomatous skin cancer,carcinoma in situ and early stage disease with a recurrence risk < 10% • Known dMMR/ MSI-H tumour status • Known hypersensitivity to oxaliplatin or fluoropyrimidine therapy • Have a peripheral sensitive neuropathy with functional impairment • Known complete DPYD deficiency (homozygosity) • Recent or concomitant treatment with brivudine, sorivudine or their chemically related analogues. For FOxTROT 3, additionally patients will not have met any of the following protocol-specific exclusion criteria: • Serious medical comorbidity, as assessed by leading clinician (such as uncontrolled angina) • Any other malignant disease within the preceding 5 years except for non-melanomatous skin cancer, carcinoma in situ and early-stage disease with a recurrence risk < 10% • Known dMMR/ MSI-H tumour status • Known hypersensitivity to oxaliplatin, irinotecan or fluoropyrimidine therapy • Have a peripheral sensitive neuropathy with functional impairment • Have a severe chronic inflammatory bowel condition. • Known complete DPYD deficiency (homozygosity) • Recent or concomitant treatment with brivudine, sorivudine (or their chemically related analogues), St John’s Wort.

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.

Study MapList of studies

Accessibility tools

Return to header