Effect of Adjunctive Metformin on Recurrence of Non-DM Colorectal Cancer Stage II High-risk/ III Colorectal Cancer

Effect of Adjunctive Metformin on Recurrence of Non-DM Colorectal Cancer Stage II High-risk/ III Colorectal Cancer: Open-label Randomized Controlled

The aim of this study is to identify the effect of adjunctive metformin on recurrence of non-DM Stage II High-risk/ III colorectal cancer. This study is open-label randomized controlled study.

The primary endpoint is to compare the 3-year disease free survival between metformin group and non-metformin group. The secondary endpoint is to compare the 5-year overall survival and disease specific survival between two group, to identify the safety of metformin, and to compare the recurrence rate of polyps after polypectomy between two groups.

Study Overview

• Status: Unknown
• Conditions: Non-DM Stage II High-risk Colorectal Cancer; Non-DM Stage III Colorectal Cancer
• Intervention / Treatment: Drug: metformin; Drug: control

• Study Type: Interventional
• Enrollment (Anticipated): 593
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Tae Il Kim, MD; Phone Number: 82-02-2228-1965; Email: taeilkim@yuhs.ac

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 120-752
    • Recruiting
    • Department of Internal Medicine, Yonsei University College of Medicine
    • Contact: TAE IL KIM, MD; Phone Number: 82-2-2228-1965; Email: taeilkim@yuhs.ac

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. patients with stage II high-risk/ III colorectal cancer who were taken an operation for cure, or patients with stage III rectal cancer who were taken an chemoradiation therapy and subsequently operation
2. age 20 - 80 years
3. patients without DM
4. patients who have well performance status for chemotherapy
5. patients who are agreed the study protocol

Exclusion Criteria:

1. patients with DM
2. patients who were diagnosed other cancers (≥ stage II) within 5 years
3. patients who have familial adenomatous polyposis, hereditary non-polyposis colorectal cancer, or inflammatory bowel disease
4. patients who are taken other chemoprevention drugs (ex. NSAIDs, Aspirin)
5. patients who have risk factors to increase lactic acidosis which are renal disease, lung disease, liver disease, or infectious disease
6. Creatinine ≥ 1.5mg/dL (for male), ≥ 1.4mg/dL (for female)
7. patients with congestive heart failure which is needed to treat
8. patients who have allergic history of metformin
9. pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: metformin	Drug: metformin; The patients of this group are treated according to NCCN guideline for stage II high-risk/ III colorectal cancer and receive an additional prescription metformin. Metformin will be prescribed 1g/day (500mg, 2 table/day, or 1000mg, 1 table/day). After adjustment period for 1month, patients who do not have side effects will be taken metformin for additional 47 months (total 48months including the adjustment period).
Active Comparator: control	Drug: control; The patients of this group are treated according to NCCN guideline for stage II high-risk/ III colorectal cancer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease free survival	The primary endpoint is to compare 3-year disease free survival between metformin group and non-metformin group.	after 3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
5-year overall survival	after 5 years
recurrence rate of polyps after polypectomy	after 1 year, and then according to the findings in 1 year colonoscopy

Collaborators and Investigators

• Sponsor: Yonsei University

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Anticipated): July 1, 2021
• Study Completion (Anticipated): July 1, 2021

Study Registration Dates

• First Submitted: November 23, 2015
• First Submitted That Met QC Criteria: November 23, 2015
• First Posted (Estimate): November 25, 2015

Study Record Updates

• Last Update Posted (Actual): September 18, 2019
• Last Update Submitted That Met QC Criteria: September 15, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Disease Attributes; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Recurrence; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: 4-2015-0533

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No