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

NCT07095517 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 25-4601OT2CA297680-01CGCATF-2023/100036
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Colorectal Cancer Prevention; Colorectal Adenoma

Keywords

colorectal cancer; colorectal cancer prevention; colorectal adenoma; obesity; incretin mimetics

Outcome Measures

Primary Outcomes (1)

• Change in Urinary PGE-M

  To determine the effect of tirzepatide intervention on urinary prostaglandin metabolites (PGE-M), an established CRC risk biomarker, in context of changes in body weight.

  From enrollment to the end of treatment at 24 weeks

Secondary Outcomes (1)

• Change in Plasma GDF-15

  From enrollment to the end of treatment at 24 weeks

Other Outcomes (2)

• Change in Microbiome

  From enrollment to the end of treatment at 24 weeks

• Change in ISC Marker Gene Expression

  From enrollment to the end of treatment at 24 weeks

Study Arms (1)

Tirzepatide

EXPERIMENTAL

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.

Drug: Tirzepatide

Interventions

Tirzepatide DRUG

Study drug injected subcutaneously once a week

Also known as: Zepbound

Tirzepatide

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-50 years Because no dosing or adverse event data are currently available on the use of tirzepatide in participants \<18 years of age, children are excluded from this study. Because we are specifically studying the prevention of EOCRC, which is defined as CRC occurring prior to age 50, the study population will only enroll participants under the age of 50 at baseline.
• BMI between 27 and 40 kg/m2
• Underwent a screening or surveillance colonoscopy within the prior 9 months.
• Removal of multiple (at least 2) colon or rectal adenomas (including sessile serrated adenomas but excluding hyperplastic polyps) or a single adenoma ≥6mm in size during the last colonoscopy
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Participants who have ever taken incretin mimetic therapies.
• Participants with a history of medullary thyroid cancer or MEN 2 syndrome.
• Participants at high risk of pancreatitis or otherwise contraindicated for use of tirzepatide according to clinical labeling.
• Participants with a history of cancer (excluding non-melanoma skin) within the last three years
• Participants with a history of diabetes mellitus
• Participants with a history of bowel surgery
• Participants with hereditary cancer syndromes, including HNPCC/Lynch syndrome or familial adenomatous polyposis
• Participants with a history of inflammatory bowel disease, Crohn's, or colitis.
• Participants with incomplete or partial polypectomy during prior colonoscopy.
• Participants who are pregnant. Participants who may become pregnant or partners of those who may become pregnant while on study will receive contraception counseling. Participants or partners of those who become pregnant while participating on the study should immediately inform their doctor.

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• Cancer Research UK: collaborator
• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms; Obesity

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Study Officials

• Andrew T. Chan, MD, MPH

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrew T. Chan, MD, MPH

CONTACT

617-726-3212; achan@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 24, 2025
• First Posted: July 31, 2025
• Study Start: February 24, 2026
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the MGB Innovation at PHSINNOVATIONSUPPORT@partners.org

Locations

US (1)