Not all bowel cancers are the same, and some treatments work better on some types than others. Tests on tumour samples may help doctors to select the best treatment for an individual patient. In the future, many cancer trials will assess biomarkers (specific molecular characteristics that distinguish different tumour types) to allocate patients into subgroups in which targeted therapies are more likely to be effective. The MRC FOCUS-3 trial was a feasibility study to assess key elements in the planning of such studies.
Patients with advanced colorectal cancer from 24 centres in the UK participated in FOCUS-3 between February 2010 and April 2011. A total of 332 patients were registered (i.e. the patients were potentially eligible and agreed to have a sample of their tumour tested to see which sub-type of bowel cancer they had). The patients’ tumour samples were analysed in one of two laboratories in Cardiff or Leeds for KRAS/BRAF oncogene mutation status and topoisomerase 1 (topo-1) immunohistochemistry. Patients were then classified into one of four molecular sub-types of bowel cancer and within each sub-type patients were randomised to one of two experimental treatments that were targeted at that sub-type of cancer, or a common control arm; 244 patients were randomised in this way.
FOCUS-3 has shown that complex prospective biomarker-driven randomised controlled trials are possible on a substantial scale across the United Kingdom. We found that patients’ tumour samples can be collected and analysed within workable time frames. Results from the testing of patient’ tumour samples were provided within 10 working days in 71% of participants, 15 working days in 91% and 20 working days in 99%.
Our four-stage patient information package and consent procedure was developed in consultation with patients and carers and was praised by the research ethics committee. Over 90% of participants felt they had excellent understanding of all aspects of the trial.
FOCUS-3 was structured so that we could address four distinct hypotheses, any or all of which might be the subject of a subsequent phase III trial. All of the trial regimens tested were shown to be safe in this phase II setting.
The central trial design concepts in FOCUS-3 have been taken forward in the FOCUS4 trial. FOCUS4 is a large Phase III trial using molecular selection of treatments for advanced bowel cancer. FOCUS4 started recruiting patients in January 2014.