The findings from FOxTROT were relased on the 19th January 2023 by the Journal of Clinical Oncology.

The results show that patients with early stage colon cancer benefit from 6 weeks of chemotherapy before surgery, with a 28% reduction to the risk of cancer coming back within 2 years.

You can view the results press release, and access links to the JCO publication and a feature by the UK Guardian newspaper in our Publications page. 

The majority of patients who die from colon cancer have had apparently curative surgery followed by postoperative chemotherapy which has failed either to clear loco-regional spread or to eradicate distant micro-metastases. Pre-operative chemotherapy for colon cancer has not previously been tested in clinical trials because of low response rates. However, there are now highly effective combination drug therapies that achieve complete or partial responses in over 50% of patients treated.

FOxTROT is a clinical trial developed by the NCRI colorectal cancer Clinical Studies Group that aims to establish whether giving the first 6 weeks of combination chemotherapy prior to surgery improves the probability of cure for patients with high-risk operable colon cancer and whether results can be further improved, in KRAS/NRAS-WT randomised to neoadjuvant chemotherapy, by adding the anti-EGFR mAB, panitumumab.

 FOxTROT is designed as a multi-centre, phase II/III study. The pilot stage of 150 patients has already been completed. The phase III trial is in progress with a target recruitment of 1050 (900 patients from phase III study). 

Patients with radiological, pre-operative staging of T4 or T3 (extramural depth ≥ 1mm), for whom Ox/FP-based chemotherapy is considered appropriate, are randomised, 2:1 between pre and post-op chemo and post-op chemo alone. Those patients allocated to pre plus post-op & shown to be KRAS/NRAS WT are randomised, 1:1, between panitumumab and not. The treatment arms are:

A) 6 weeks of pre-op OxFP chemotherapy followed by surgery then 18 (or 6) weeks post-op OxFP chemo

B) The same chemotherapy with concomitant panitumumab for the first 6 weeks

C) Surgery then 24 (or 12) weeks of post-op OxFP chemo

Primary objective:

• Does neoadjuvant chemotherapy ± panitumumab followed by deferred surgery & post-op chemo reduce 2 year recurrence?
• Does adding panitumumab neo-adjuvantly increase anti-tumour efficacy as measured by tumour shrinkage, for KRAS/NRAS Wildtype patients?

Secondary objectives:

To assess:

• Accuracy of pre-treatment CT scan staging
• Tolerability of neoadjuvant therapies
• Nature and frequency of surgical complications
• Prognostic & predictive value of tumour biomarkers
• The influence of resectional quality on outcome

Primary outcomes:

• For comparison of pre– plus post-op chemo, the primary outcome is freedom from recurrence at 2-years post-randomisation.
• For the comparison of preoperative chemotherapy ± panitumumab, the primary outcome is pathological downstaging, measured by depth of extramural spread.

Secondary outcomes:

• Death from colon cancer
• Overall survival
• Pathological assessment of down-staging
• Radiological assessment of response to neoadjuvant chemo
• Quality of life
• Surgical morbidity/mortality
• Chemotherapy toxicity

The final results of the FOxTROT trial were presented at the 2019 ASCO annual meeting in Chicago by Professor Matt Seymour. The presentation received a very positive reaction from the panel with enthusiasm and excitement about what it could bring.

For more updates on this and the future of FOxTROT please see the new FOxTROT Twitter account @FOxTROTStudy.

Recruitment target was successfully reached in December 2016 and 1053 patients were randomised into the trial.  

Thank you for your continuous support of this trial!

On 24th March 2016 the 950th FOxTROT patient entered the trial. This means we are now just 100 patients away from our final target of 1050!

Congratulations to the team at Harrogate District Hospital: Principal Investigator Dr Kim Last, and Lead Nurse Nicky Thomas, for helping us reach this milestone.

Thank you to all recruiting centres for your continued support.

The recruitment phase of FOxTROT is still ongoing, please continue to screen and enter patients.

We hope to complete recruitment by the end of 2016. A no-cost extension has been submitted to CRUK.

On 24th November 2015 panitumumab Investigator's Brochure version 14.0 (15th July 2015) was sent to Local Principal Investigator's, Lead Oncologists (if the local PI is a surgeon) and Lead Pharmacists at all FOxTROT sites which offer panitumumab.

Please use IB version 13.0, 1st April 2014 as the Reference Safety Information for panitumumab. However, please refer to the new version of the IB for all other panitumumab-related information.

On 13th November the 900th FOxTROT patient entered the trial!

Thank you to all recruiting centres for your continued support.

On 26th March the 800th patient was entered onto the trial!

Thank you to all recruiting centres for your continued support.

On 14th October all FOxTROT forms were updated. These new forms have been distributed to sites for immediate implementation.

For a list of all current forms please visit the Trial documentation link in the For Investigators section of the website.

On 5th August the 700th patient was entered onto the trial, meaning the trial is now 2/3rds of the way through recruitment!

Thank you to all recruiting centres for your continued support.

Following approval in July 2013 of a No-Cost extension until 31-Oct-2014 we received in January 2014 approval of a costed extension from 01-Nov-2014 to 31-Mar-2018.

This includes an extension to the trial's recruitment until 31-Dec-2015.

In July 2013 there were 22 patients randomised into the trial; over 20% more than the next highest recruiting month back in June 2011 which saw 18 patients were entered into the trial.

Thank you to all those centers who helped make it our best month so far and to all centers open for FOxTROT for your continued support for the trial.

The end of 2012 and beginning of 2013 saw the first of several international centres opening to recruitment - 3 centres in Denmark; Aarhus, Aalborg and Odense University Hospitals. Furthermore the first international patient was randomised in March 2013 by Aarhus University Hospital.

Following the completion of recruitment into the pilot phase in 2010, results from the first 150 patients have been analysed and the results published in the Lancet Oncology (online Sep 2012, journal Nov 2012).

• The Lancet Oncology doi:10.1016/S0140-6736(08)61345-8: Feasibility of preoperative chemotherapy for locally advanced, operable colon cancer: the pilot phase of a randomised controlled trial.

TheFOxTROT protocol v6.0 (09/07/2012) has now been approved.

We are currently in the process of notifying the R&D department of the sites involved with the trial. Please contact the FOxTROT office if you are unsure whether your site has received all the latest documentation. The changes to the protocol were as follows:

1. Removal of Arm D; post-operative chemotherapy plus panitumumab.

Following the publication of results from a recent study (the Intergroup NO147 trial) post-operative panitumumab was withdrawn from FOxTROT, i.e. Arm D of the trial was removed. As you will be aware, this change was implemented in summer 2011 as an urgent safety measure with immediate effect. The new version of the FOXTROT protocol, v6.0; 9th July 2012, fully details this change.

2. Updating of clinical trial evidence on EGFR-directed monoclonal antibody therapies.

3. Clarifications of trial eligibility criteria.

This includes clarification that patients with high-grade dysplasia on histology plus unequivocal radiological evidence of cancer are eligible for the trial.

4. Removal of the interval CT scan.

The CT scan after neoadjuvant chemotherapy, prior to surgery is now no longer required.

5. New versions of the Patient Information Sheet, consent form and GP letter.

The PIS and consent form have been updated to reflect the removal of post-operative panitumumab. The current version of these two documents is version 4.0. The GP letter has also been updated and is now version 3.0.