Individuals with a specific type of tumour will receive an immunotherapy drug called dostarlimab before surgery, rather than the standard procedure where surgery is carried out first, then sometimes followed up by chemotherapy.
This is the first trial to specifically test the outcomes of this approach in older patients with the disease.
FOxTROT 5, led by the University and supported by the NIHR Leeds Clinical Research Facility, heralds a step towards more personalised, precision oncology in colon cancer patients.
People with the disease, who are at least 70 years old, or have significant additional medical conditions, may be able to take part in the trial, which will be running at 20 hospitals across the UK.
It is hoped that the results will inform standard practice, providing evidence of whether this approach could be safe and effective for these types of patients.
The University of Leeds is the trial sponsor, with its Clinical Trials Research Unit (CTRU) leading the study alongside clinicians. The University’s NHS partner site is St James’s University Hospital – Leeds Teaching Hospitals NHS Trust.
The trial will use dostarlimab to target “deficient mismatch repair” (dMMR) colon cancer – a molecularly distinct colon cancer that has been shown in other trials to respond extremely well to immunotherapy.
Cancer immunotherapies are treatments that use the immune system to find and attack cancer cells. There are several different types and they each use the immune system in a different way and can be administered in various ways.
Addressing health inequality
Professor Jenny Seligmann, Chief Investigator of the FOxTROT programme and Consultant Medical Oncologist at Leeds Teaching Hospitals NHS Trust, said: “This approach has already proved to be good for many younger patients but there’s a lack of evidence for what works for older patients. That’s a significant health inequality, which we hope to address.
“The purpose of FOxTROT 5 is to find an improved treatment for colon cancer patients that have cancer cells with an abnormality called dMMR. Standard chemotherapy treatments can be less successful for these patients.
“We hope this trial will lead to a new treatment for them, as well providing further understanding of the disease for the future.”
The £2.6million project, funded by biopharma company GSK, is being run in collaboration with the University of Glasgow and University of Birmingham. The project is part of the FOxTROT Trial Platform funded by Yorkshire Cancer Research.
Every year, over 44,000 people in the UK are diagnosed with colon cancer and over 16,000 lose their lives because of it.
Patients are usually treated with surgery first and may go on to have chemotherapy afterwards to help prevent the cancer coming back.
However, often old, frail patients aren’t well enough to undergo surgery or necessary anti-cancer treatment afterwards. Delivering an immunotherapy treatment first could prevent that, if this approach is successful.
Most people who develop colon cancer are classed as older or frail, but that group of people isn’t usually eligible for clinical trials, meaning there is little evidence for what works best for them.
FOxTROT 5 is aimed at helping to address that health inequality.
Previous success
The FOxTROT trial platform now has options for most stage 2 and 3 colon cancer patients and has seen great success.
FOxTROT 1, a collaborative study by scientists at Leeds and the University of Birmingham, showed that giving proficient mismatch repair (pMMR) colon cancer patients chemotherapy before, rather than after, surgery reduced the chance of the disease returning within two years by more than a quarter.
The new approach to treating colon cancer has since become a treatment option under NICE (the National Institute for Health and Care Excellence) guidelines.
FOxTROT 2 tests whether the approach works in older, frailer pMMR patients.
FOxTROT 3 is investigating whether more intensive chemotherapy can further improve benefits in pMMR patients who can tolerate it. Both are funded by Yorkshire Cancer Research.
FOxTROT 4 tests targeted oncology treatment in pMMR colon cancer patients with an abnormality in their tumour called a BRAF mutation. These patients currently have particularly poor outcomes.
The launch of FOxTROT 5 means the trial platform now, in theory, offers a trial for all the older and frail stage 2 and 3 colon cancer patients, although some further checks are required for each patient to ensure the trial is suitable for them.
Dr Stuart Griffiths, Director of Research at Yorkshire Cancer Research, said: “The launch of FOxTROT 5 marks a significant development in the FOxTROT Trial Platform and aligns with the charity’s ambition to bring potential benefits from the research to as many people with bowel cancer as possible, in Yorkshire and across the globe. We are grateful to the charity’s supporters for helping to create an important and unique opportunity for Yorkshire to drive forward this exciting research.”
FOxTROT 5 will be launched at 20 hospitals across the UK in the coming months, with the following already offering the trial to patients:
Ninewells Hospital, Dundee
St James’s University Hospital, Leeds
Churchill Hospital, Oxford
Queen’s Hospital Burton
Queen Elizabeth Hospital Birmingham
University Hospital, Coventry
Ipswich Hospital.
To find out more about how you or a family member could take part in FOxTROT 5, please speak to your hospital doctor.