FOxTROT
FOxTROT - Fluoropyrimidine, Oxaliplatin and Targeted Receptor Pre-Operative Therapy: a Controlled Trial in High-Risk Operable Colon Cancer
Phase 2/3N = 1,053NCT00647530
- Population
- Patients with operable, radiologically staged T3-4 N0-2 M0 colon cancer; 699 allocated to NAC and 354 to control (ClinicalTrials.gov actual enrolment 1053).
- Design
- International randomised trial. Patients with radiologically staged T3-4 N0-2 M0 colon cancer were allocated 2:1 to 6 weeks of oxaliplatin-fluoropyrimidine chemotherapy before surgery plus 18 weeks after (neoadjuvant, NAC) or 24 weeks after surgery (control). Patients with RAS-wild-type tumours could also be randomised 1:1 to panitumumab or not during NAC. Primary endpoint residual disease or recurrence within 2 years; log-rank analyses by intention to treat.
- Primary endpoint
- Residual disease or recurrence within 2 years
- Arms
- Neoadjuvant chemotherapy (experimental, n = 699): 6 weeks of oxaliplatin-fluoropyrimidine before surgery plus 18 weeks after surgery
- Postoperative chemotherapy (control, n = 354): 24 weeks of oxaliplatin-fluoropyrimidine after surgery
- Neoadjuvant FOLFOX plus panitumumab (experimental): Embedded randomisation in RAS/BRAF-wild-type patients: preoperative FOLFOX plus panitumumab
- Neoadjuvant FOLFOX (control): Embedded randomisation in RAS/BRAF-wild-type patients: preoperative FOLFOX alone
- People
- Morton D, FOxTROT Collaborative Group
Δ Residual disease or recurrence within 2 years−4.6 pointsΔ Histopathologically complete resection+5 pointsTime to recurrenceHR 0.51
Show the numbers
| Endpoint | Analysis | Neoadjuvant chemotherapy / Neoadjuvant FOLFOX plus panitumumab | Postoperative chemotherapy / Neoadjuvant FOLFOX | Effect |
|---|---|---|---|---|
| Residual disease or recurrence within 2 years | primaryMorton 2023 | 16.9% | 21.5% | P=0.037Rate ratio 0.72 (95% CI 0.54 to 0.98), not a hazard ratio: 118 of 699 versus 76 of 354. 674 of 699 (96 percent) started and 606 (87 percent) completed NAC; 30 patients (4.3 percent) developed obstructive symptoms requiring expedited surgery. Little benefit was seen in mismatch repair-deficient tumours (no figures in the abstract). |
| Histopathologically complete resectionPatients who underwent surgery (686 NAC, 351 control) | primaryMorton 2023 | 94% | 89% | P<0.001Secondary outcome: 648 of 686 versus 311 of 351. Surgery was performed in 686 of 699 (98.1 percent) NAC patients and 351 of 354 (99.2 percent) control patients. |
| Time to recurrenceRAS/BRAF-wild-type patients in the embedded randomised phase II comparison (169) | exploratorymedian follow-up 42 monthsSeligmann 2025 | — | — | HR 0.51P=0.09In 169 RAS/BRAF-wild-type patients. Time to recurrence was the primary endpoint of this embedded phase II comparison, which the authors call exploratory. The abstract reports recurrences in 12% with FOLFOX plus panitumumab and 21% with FOLFOX alone (no time point), which are not time-to-recurrence rates and are held here. The abstract states significant improvements for disease-free survival, colon cancer-specific survival and overall survival without giving figures. Grade 3 diarrhoea 8 percent versus 3 percent and rash 22 percent versus 2 percent with panitumumab. |
| Endpoint | Analysis | Neoadjuvant chemotherapy / Neoadjuvant FOLFOX plus panitumumab | Postoperative chemotherapy / Neoadjuvant FOLFOX | Effect |
|---|---|---|---|---|
| Residual disease or recurrence within 2 years | primaryMorton 2023 | 16.9% | 21.5% | P=0.037Rate ratio 0.72 (95% CI 0.54 to 0.98), not a hazard ratio: 118 of 699 versus 76 of 354. 674 of 699 (96 percent) started and 606 (87 percent) completed NAC; 30 patients (4.3 percent) developed obstructive symptoms requiring expedited surgery. Little benefit was seen in mismatch repair-deficient tumours (no figures in the abstract). |
| Histopathologically complete resectionPatients who underwent surgery (686 NAC, 351 control) | primaryMorton 2023 | 94% | 89% | P<0.001Secondary outcome: 648 of 686 versus 311 of 351. Surgery was performed in 686 of 699 (98.1 percent) NAC patients and 351 of 354 (99.2 percent) control patients. |
| Time to recurrenceRAS/BRAF-wild-type patients in the embedded randomised phase II comparison (169) | exploratorymedian follow-up 42 monthsSeligmann 2025 | — | — | HR 0.51P=0.09In 169 RAS/BRAF-wild-type patients. Time to recurrence was the primary endpoint of this embedded phase II comparison, which the authors call exploratory. The abstract reports recurrences in 12% with FOLFOX plus panitumumab and 21% with FOLFOX alone (no time point), which are not time-to-recurrence rates and are held here. The abstract states significant improvements for disease-free survival, colon cancer-specific survival and overall survival without giving figures. Grade 3 diarrhoea 8 percent versus 3 percent and rash 22 percent versus 2 percent with panitumumab. |
Appears in
Sources
Morton D, Seymour M, Magill L, Handley K, Glasbey J, Glimelius B, et al. Preoperative Chemotherapy for Operable Colon Cancer: Mature Results of an International Randomized Controlled Trial. J Clin Oncol. 2023;41(8):1541-1552.
Seligmann JF, Morton D, Elliott F, Handley K, Gray R, Seymour M, et al. Neo-adjuvant FOLFOX with and without panitumumab for patients with KRAS-wt locally advanced colon cancer: results following an extended biomarker panel on the FOxTROT trial embedded phase II population. Ann Oncol. 2025;36(5):520-528.