Clinical trial NCT01550900: Prospective Trial of Metformin - Chemoprevention Role
Official title: A Prospective Placebo-control Double-blind Randomized Trial of Metformin in Chemoprevention of Metachronous Colonic Neoplastic Polyps
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Colorectum
Keywords: Colorectum
Metachronous ctalColonic Neoplastic Polyps
Chemoprevention
Colonic adenoma(s)
Pre-cancerous tumor(s) on the colon
Metformin ER
Extended Release
Placebo
Sugar pill
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
First posted: 2012-03-12
Enrollment: 0
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical research study is to learn if metformin extended release (ER) can prevent colonic adenomas from becoming cancerous. Metformin ER will be compared to a placebo.

Metformin ER is designed to block a protein in tumor cells that is important in tumor growth and blood vessel development. This may cause cell death or reduce the spread of the disease.

A placebo is not a drug. It looks like the study drug but is not designed to treat any disease or illness. It is designed to be compared with a study drug to learn if the study drug has any real effect.

Detailed description: Colonic adenomas are considered pre-cancerous, but they may change into colorectal cancer. Patients have a higher risk of developing additional adenomas if adenomas are found at the time of their follow-up colonoscopy.

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 groups. You will have an equal chance of being assigned to either group.

If you are in Group 1, you will receive metformin ER

If you are in Group 2, you will receive a placebo.

Neither you nor the study staff will know if you are receiving the study drug or the placebo. However, if needed for your safety, the study staff will be able to find out what you are receiving.

Study Drug Administration:

You will take metformin ER/placebo tablets by mouth 1 time a day with food for 12-18 months (usually 12 months but sometimes up to 18 if the doctor thinks it is needed). This will allow time for at least 1 repeat follow-up colonoscopy.

The dose of metformin ER will be increased at Week 2 and again at Week 3. If you have side effects, the dose may be lowered if the doctor thinks it is needed.

Study Visit:

At 3-12 months or 3-18 months after you start taking metformin ER/placebo, you will have another colonoscopy and standard tissue collection for colonic adenoma(s). This tissue will be used for biomarker testing. Blood (about 3 tablespoons) will be drawn for testing on your blood sugar and for biomarker testing. You will need to fast for 8 hours before this test.

Your blood and tissue will also be used for research on the cause of colorectal cancer and biomarker testing.

Length of Treatment:

You may continue taking the study drug for 12 months. However, if your doctor thinks it is needed, a follow-up colonoscopy may be scheduled for you at either 15 or 18 months after enrollment. If this is the case, you will continue taking the drug for up to 18 months. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over once you have completed the study visit.

This is an investigational study. Metformin ER is FDA approved and commercially available for the treatment of type 2 diabetes. Its use to prevent colonic adenomas is investigational.

Up to 128 patients will take part in this study. All will be enrolled at MD Anderson.

Eligibility criteria: Inclusion Criteria:

1. Age between 40 and 75 years
2. Polyp features suggesting high risk for recurrence include: piece-meal polypectomy, large (\>10mm) neoplastic polyp, polyp with high grade dysplasia, or substantial number (\>10) of neoplastic polyps.
3. ability to give informed consent
4. Patients should be registered on LAB10-0417
5. Diabetic patients are eligible but they may be excluded if they are taken Metformin, insulin or sulfonylureas

Exclusion Criteria:

1. Patients with renal insufficiency defined as serum creatinine \>= 1.4 mg/dl for females and \>= 1.5 mg/dl for males by the manufacturer.
2. Pregnant or nursing women
3. A malignancy currently under active therapy
4. Unstable angina, uncontrolled ischemic cardiac disease or symptomatic congestive heart failure (e.g. Class III or IV New York Heart Association's Functional Classification)
5. Current usage of Metformin
6. Current usage of insulin, sulfonylureas
7. History of lactic acidosis
8. Liver dysfunction including chronic active hepatitis and cirrhosis
9. Inability to give informed consent
10. Other investigational drugs within the past one year or concurrently
11. Known hypersensitivity or intolerance to Metformin
12. Contraindications for repeat colonoscopy
13. Inflammatory bowel disease
14. Rectosigmoiditis of any etiology

Primary outcomes:
measure: Percentage of Ki-67-Stained Nuclei in Normal Rectal Mucosa
timeFrame: 3 months
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: UT MD Anderson Cancer Center
name: William Ross, MD
role: PRINCIPAL_INVESTIGATOR
References: