FOxTROT trial

Fluoropyrimidine, Oxaliplatin and Targeted-Receptor pre-Operative Therapy for patients with high-risk, operable colon cancer

The FOxTROT Trial will 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. It will also determine if, in patients with KRAS-wt tumours, adding panitumumab to neoadjuvant therapy increases anti-tumour activity as measured by tumour shrinkage.

The Rationale for a Trial

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-WT randomised to neoadjuvant chemotherapy, by adding the anti-EGFR mAB, panitumumab.

Trial Design

 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 appro-priate, 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 WT are randomised, 1:1, between panitumumab and not. The treat-ment 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

 FOxTROT Trial Design 

Objectives

Primary objective:

  • Does neoadjuvant chemotherapy ± panitumumab followed by deferred surgery & post-op chemo reduce 2 year recurrence?
  • Does adding panitumumab neoad-juvantly increase anti-tumour effi-cacy as measured by tumour shrink-age, for KRAS WT patients?

Secondary objectives:

To assess:

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

Outcome Measures

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

What's the latest....

August 2014 - 700th patient recruited!

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

Thank you to all recruiting centres for your continued support.

January 2014 - Extension Approval!

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.

July 2013 - New all time high monthly recruitment

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.

Mar 2013  - International Recruitment!!!

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.

Nov 2012 - FOxTROT Pilot Paper published!!!

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).

Sep 2012 - New Protocol!!!

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

We are currently in the porcess 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 nequivocal 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.

Randomisation

To randomise a patient please call 0800 953 0274 or log into:

https://www.trials.bham.ac.uk/FOxTROT

If you do not have log in details please contact the FOxTROT office who will be able to set these up for you.

FOxTROT Study Office

Email:  FOxTROT-trial@contacts.bham.ac.uk

Laura Magill (Trial Manager)  Tel:0121 415 9105 Email:  e.l.magill@bham.ac.uk

Andy Palmer  (Trial Administrator)  Tel:0121 414 9013 Email:  a.palmer@bham.ac.uk

Georgia Kennedy (Data Manager)  Tel:0121 414 9013 Email:  g.kennedy@bham.ac.uk 

 

 FOxTROT Logo

 

FOxTROT

EudraCT Number: 2007-001987-55

REC West Glasgow: 07/S0703/57

ISRCTN87163246

 

FOxTROT Protocol v6.0 (09/07/12)

 

Online Randomisation

 

Contact the FOxTROT Team