NCT01312467

Trial of Metformin for Colorectal Cancer Risk Reduction for History of Colorectal Adenomas and Elevated BMI

A Phase IIa Trial of Metformin for Colorectal Cancer Risk Reduction Among Patients With a History of Colorectal Adenomas and Elevated Body Mass Index

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 45 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 35 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to find out whether METFORMIN decreases protein markers in colorectal tissue. This is a phase IIA study of the pharmacodynamics, safety and tolerability of Metformin in decreasing colorectal mucosa in patients with a history of colorectal adenomas in the past 3 years and a BMI \>= 30, with decimals rounded to the nearest whole integer. Metformin as a potential chemopreventive agent for inhibition of the relevant molecular pathways involved in human colorectal carcinogenesis.

Detailed description

PRIMARY OBJECTIVES: I. To determine if a 12-week intervention of oral metformin (metformin hydrochloride) treatment among obese patients with a history of colorectal adenomas results in at least a 35% decrease in colorectal mucosa activated pS6serine235 from baseline as assessed via immunostaining. SECONDARY OBJECTIVES: I. To assess the effect of metformin on additional relevant biomarkers in serum: metformin levels; fasting insulin-like growth factor (IGF)-1, insulin-like growth factor binding protein (IGFBP)-1, IGFBP-3; fasting leptin; fasting Adiponectin; fasting and 2 hour post-prandial insulin and glucose. II. To examine the correlation among biomarkers (serum, tissue). III. To assess the independent effects of treatment on each biomarker, using multivariate regression models to account for clinical and biomarker data. IV. To document the safety and tolerability of metformin in the study population. TERTIARY OBJECTIVES: I. To assess the effect of metformin on additional relevant biomarkers in tissue via immunostaining. This will include the effects on levels of colorectal mucosa proliferation estimated by: phosphorylated AMPK (pAMPK), phosphorylated AKTserine 473 (pAKT), phosphorylated mTOR, phosphorylated insulin receptor (pIR), phosphorylated IGF-1 (pIGF-1) receptor, and Ki-67. II. To cross-validate immunostaining results with Western blotting experiments in a subset of consecutive patients for the following endpoints: phosphorylated S6serine235 (pS6serine235), phosphorylated AMPK (pAMPK), phosphorylated AKTserine 473 (pAKT), phosphorylated mTOR, phosphorylated insulin receptor (pIR), phosphorylated IGF-1 (pIGF-1) receptor, and Ki-67. OUTLINE: Patients receive metformin hydrochloride orally (PO) once daily (QD) during week 1 and then twice daily (BID) during weeks 2-12. Treatment continues for 12 weeks in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed up for 4 weeks.

Conditions

• Adenomatous Polyp
• Colorectal Cancer
• Obesity

Interventions

Type	Name	Description
DRUG	metformin hydrochloride

Timeline

• Start date: 2011-03-01
• Primary completion: 2014-03-01
• Completion: 2014-12-01
• First posted: 2011-03-10
• Last updated: 2019-03-05
• Results posted: 2015-06-25

Locations

4 sites across 2 countries: United States, Canada