Pathways, Risk Factors, and mOleculeS to Prevent Early-onset Colorectal Tumors

Overview

This research study is an open-label Phase 1 Exploratory/Pilot clinical trial to measure the effects of the incretin mimetic, tirzepatide, on tissue, urine, blood, and microbiome biomarkers associated with colorectal cancer risk and to understand the feasibility of this precision prevention trial approach for a future larger study.

In this research study, we are: * Investigating the effects of tirzepatide on biomarkers of colorectal cancer risk in patients with a recent diagnosis of adenoma, a type of intestinal polyp that can precede the development of cancer. * Planning to measure the potential protective effects associated with tirzepatide within biological samples (biospecimens) including stool, urine, blood, and oral swab samples collected prior to, during, and after treatment with tirzepatide. * Tirzepatide is a part of the incretin mimetic (GLP-1 receptor agonist) family, which are typically used for managing diabetes and/or obesity. * Tirzepatide may prevent colorectal cancer through multiple possible biological mechanisms. This includes weight loss which can reduce the risk of developing obesity-associated cancers, such as colorectal cancer. * Tirzepatide has been shown to effectively induce weight loss and improve glycemic control. The exact mechanism by which tirzepatide acts to prevent colorectal cancer is still unknown. By performing this research study, we will study the mechanisms of its anti-cancer effect, which may lead to the discovery of novel specific characteristics (markers) that can be used to select patients for tirzepatide treatment to reduce risk of cancer in the future. The research procedures include screening for eligibility and study treatment and scheduling four clinical research visits: * Initial visit - immediately before starting the study drug * Week 1 visit * Midpoint visit (9-12 weeks later) (Midpoint visit) * Final visit (after completing the drug intervention) At the Initial and Final visits, a flexible sigmoidoscopy will be performed along with the collection of body measurements, questionnaire data, blood, urine, saliva, stool, and up to 24 tissue biopsy samples. The first dose of the study drug will be administered by study staff at the initial visit. Participants will self-administer the second dose of the study drug at the Week 1 visit under supervision of study staff. At the Week 1 and Midpoint visits, they will also provide body measurements, blood, urine, saliva, and stool samples. Participants will be instructed to inject tirzepatide 1 time per week for up to 24 weeks. The dose will start with a 2.5mg injection per week for the first 4 weeks. Dose will increase 2.5mg/injection every 4 weeks until 15mg/injection (or maximum tolerable dose) per week is reached. Participants will be followed weekly during this time. In the very rare occasion that there are unavoidable issues scheduling the final visit, treatment may be extended up to an additional 4 weeks. It is expected that about 20 people will take part in this research study. This research is being supported by The Cancer Grand Challenges partnership funded by Cancer Research UK, the National Cancer Institute, the Bowelbabe Fund for Cancer Research UK and Institut National Du Cancer.

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Central Contacts