| Objective: |
FOxTROT is a phase III, multi-centre randomised controlled trial aiming to establish whether giving 6 weeks of standard chemotherapy preoperatively (neoadjuvantly) can improve outcome for patients with high?risk, operable colon cancer, compared with the same total amount of chemotherapy delivered in the standard, postoperative setting. Also, FOxTROT trial aims to assess whether adding the anti EGFR monoclonal antibody, panitumumab to neoadjuvant therapy, in patients with RAS- wildtype tumours, can improve treatment efficacy. |
| Aim: |
Primary objectives:
•To determine if neoadjuvant chemotherapy ± panitumumab followed by deferred surgery then completion of chemotherapy post-operatively reduces 2-year recurrence compared to standard surgery and postoperative chemotherapy.
•To determine if, in patients with RAS-wt tumours, adding panitumumab to neoadjuvant therapy increases anti-tumour activity as measured by tumour shrinkage.
Secondary objectives:
•To assess the accuracy of pre-treatment CT scan staging.
•To assess the tolerability of the neoadjuvant therapies.
•To assess the nature and frequency of surgical complications.
•To measure the impact of the treatments on patient's quality of life and resource usage. •To assess whether adding panitumumab to neoadjuvant CT reduces 2-year recurrence. •To assess the prognostic and predictive value of tumour biomarkers.
•To assess the influence of resectional quality on outcome.
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| Methods: |
Every patient in FOxTROT is randomised, in a 2:1 ratio, to receive either pre-plus-post-operative therapy (6 weeks preoperative; remainder postoperative) or the same total duration given as standard post-operative chemotherapy. In addition, following RAS testing of the primary tumour, patients established to have RAS-wt tumours who are allocated preoperative CT are randomised, in a 1:1 ratio, to receive panitumumab with the first 6 weeks of chemotherapy or to control. Thus, the three treatment arms for patients with RAS-wt tumours are: A) Six weeks of pre-operative oxaliplatin/fluoropyrimidine (OxFP) chemotherapy followed by surgery then 18 (or, optionally, 6) weeks of post-operative OxFP chemotherapy. B) The same chemotherapy regimen with concomitant panitumumab for the first 6 weeks. C) Surgery then 24 (or, optionally, 12) weeks of post-operative OxFP chemotherapy. Patients with RAS-mutant tumours, and patients at centres not taking part in the panitumumab randomisation, are randomised just between arms A and C.
Inclusion Criteria:
• Histologically proven adenocarcinoma of the colon or high grade dysplasia on histology plus unequivocal radiological evidence of invasive cancer.
• A candidate for adjuvant oxaliplatin/ fluoropyrimidine chemotherapy based on: - Either radiological high risk (rT4 or rT3 tumour with extramural extension ≥ 5mm) - Or radiological intermediate risk (rT3 tumour with 3.0 x109/l; Plts >100 x109/l. Anaemia (Hb 50 ml/min calculated by the Wright or Cockroft formula or EDTA clearance >70 ml/min • Adequate hepatobiliary function: bilirubin ged 18 or over
• WHO performance status of 0, 1 or 2
• If female and of childbearing potential, must: - Have a negative pregnancy test ≤72hours prior to initiating study treatment - Agree to avoid pregnancy during and for 6 months after study treatment
• If male with a partner of childbearing potential, must: - Agree to use adequate, medically approved, contraceptive precautions during and for 90 days after the last dose of study treatment
• Patient able and willing to provide written informed consent for the study
Exclusion criteria:
• Any patient for whom radiotherapy is advised by the MDT
• Strong evidence of distant metastases or peritoneal nodules (M1)
• Peritonitis (secondary to perforated tumour)
• Colonic obstruction that has not been defunctioned
• Serious medical comorbidity, eg uncontrolled inflammatory bowel disease, uncontrolled angina or recent ( |
| Reason for International Trial: |
To establish an international network which will be utilised for future trials. |