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

Study Overview
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Brief Summary
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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.

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

Conditions
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Non-DM Stage II High-risk Colorectal Cancer, Non-DM Stage III Colorectal Cancer

Intervention / Treatment
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* Drug: metformin
* Drug: control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 age 20 - 80 years patients without DM patients who have well performance status for chemotherapy patients who are agreed the study protocol Exclusion Criteria: patients with DM patients who were diagnosed other cancers (≥ stage II) within 5 years patients who have familial adenomatous polyposis, hereditary non-polyposis colorectal cancer, or inflammatory bowel disease patients who are taken other chemoprevention drugs (ex. NSAIDs, Aspirin) patients who have risk factors to increase lactic acidosis which are renal disease, lung disease, liver disease, or infectious disease Creatinine ≥ 1.5mg/dL (for male), ≥ 1.4mg/dL (for female) patients with congestive heart failure which is needed to treat patients who have allergic history of metformin pregnancy

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: metformin<br> | Drug: metformin<br>* 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).<br>|
| Active Comparator: control<br> | Drug: control<br>* The patients of this group are treated according to NCCN guideline for stage II high-risk/ III colorectal cancer.<br>|

What is the study measuring?
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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 | Measure Description | 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 |