CRUK/19/011 COLO-PREVENT; A platform for developing COLOrectal cancer PREVENTion therapies

Background Colorectal cancer (CRC) is the second most common cause of cancer death in the UK.

Population aging and the increase in obesity and type 2 diabetes, both risk factors for CRC, are likely to magnify the problem in future decades.

Prevention, through the use of safe and effective therapies offers a largely untapped strategy for reducing the incidence and mortality due to CRC.

Such therapies could be employed for primary prevention, and in conjunction with screening programmes in patients considered ‘high-risk’ due to the detection of premalignant adenomas.

COLO-PREVENT is a unique multicentre phase 2/3 trial platform for evaluating the efficacy of cancer preventive therapies that is embedded within the Bowel Cancer Screening Programme.

It will recruit patients deemed ‘high-risk’ for the development of metachronous colorectal polyps and/or cancer after clearing colonoscopy. Aims: 1. To determine whether metformin plus aspirin is superior to aspirin alone. 2.

To assess whether resveratrol has any effect on polyp recurrence and identify the most active dose in a signal-seeking trial.

Methods The design of COLO-PREVENT is based on the seAFOod trial, which was the first CTIMP carried out in the English BCSP and which established protocols and RCT infrastructure at screening sites.

BCSP patients aged between 55–73.5-years, identified according to BCSP criteria as ‘high-risk’ at the first complete screening colonoscopy, will be randomised to aspirin (Standard of Care) or aspirin plus metformin for three years.

For the parallel resveratrol signal-seeking phase 2 trial, participants either already on, or intolerant to aspirin or metformin, will be randomised to two doses of resveratrol or placebo for 12 months.

The primary endpoint is adenoma recurrence (MAP), secondary endpoints include adenoma detection rate (ADR), advanced adenomas, adenoma subtype and location, adverse events and compliance.

Research endpoints will focus on the association between metabolic status and treatment efficacy, assessment of pharmacodynamic biomarkers and role of the gut microbiome in predicting and mediating the effects of the three therapies. How the results of this research will be used.

We anticipate our results will identify a number of safe effective therapies that can be used in conjunction with screening to prevent polyp recurrence and ultimately decrease CRC risk.

Inclusion of the sub-trial is an innovative way to establish a pipeline for testing other promising therapies and interventions, generating the first evidence of clinical efficacy.

COLOPREVENT will provide a long-term platform for testing therapies, other lifestyle/behavioural interventions and novel combinations.