A Prospective Placebo-control Double-blind Randomized Trial of Metformin in Chemoprevention of Metachronous Colonic Neoplastic Polyps
40 Years
75 Years
Both
Colorectum
Trial Information
A Prospective Placebo-control Double-blind Randomized Trial of Metformin in Chemoprevention of Metachronous Colonic Neoplastic Polyps
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.
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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Outcome Measure:
Percentage of Ki-67-Stained Nuclei in Normal Rectal Mucosa
Outcome Description:
Primary endpoint defined as change in overall proliferation index between baseline and first return visit, that is, percentage of Ki-67-stained nuclei, in normal rectal mucosa. Tissue samples will be obtained at baseline colonoscopy and subsequent exams for analysis including Ki67, caspase 3, and various biomarkers and immunohistochemicals studies.
Outcome Time Frame:
3 months
Safety Issue:
No
Principal Investigator
William Ross, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
UT MD Anderson Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
2011-1100
NCT ID:
NCT01550900
Start Date:
July 2013
Completion Date:
Related Keywords:
- Colorectum
- Colorectum
- Metachronous ctalColonic Neoplastic Polyps
- Chemoprevention
- Colonic adenoma(s)
- Pre-cancerous tumor(s) on the colon
- Metformin ER
- Extended Release
- Placebo
- Sugar pill
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