Prospective Trial of Metformin - Chemoprevention Role

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01550900
First received: March 8, 2012
Last updated: April 4, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention
Colorectum
Drug: Metformin ER
Other: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Prospective Placebo-control Double-blind Randomized Trial of Metformin in Chemoprevention of Metachronous Colonic Neoplastic Polyps

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Percentage of Ki-67-Stained Nuclei in Normal Rectal Mucosa [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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.


Enrollment: 0
Study Start Date: July 2013
Estimated Primary Completion Date: July 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Metformin ER
Participants receive two tablets of Metformin ER 500 mg once daily for no more than twelve to eighteen months allowing time for at least one follow up colonoscopy. Dose will be reached in a gradual escalation scheme to improve gastrointestinal tolerance. If participants experience side effects during dose escalation regimen, they will be reduced to one tablet of 500 mg daily, and may continue taking 500 mg daily for the duration of the study.
Drug: Metformin ER
Starting dose: 500 mg by mouth daily for 1 week with weekly increases of 250 mg daily to target dose of 1000 mg daily.
Active Comparator: Placebo
Control group given matched Placebo once daily for no more than twelve to eighteen months allowing time for at least one follow up colonoscopy.
Other: Placebo
Placebo tablets by mouth 1 time a day.
Other Name: sugar pill

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

Ages Eligible for Study:   40 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01550900

Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: William Ross, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01550900     History of Changes
Other Study ID Numbers: 2011-1100
Study First Received: March 8, 2012
Last Updated: April 4, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Colorectum
Metachronous ctalColonic Neoplastic Polyps
Chemoprevention
Colonic adenoma(s)
Pre-cancerous tumor(s) on the colon
Metformin ER
Extended Release
Placebo
Sugar pill

Additional relevant MeSH terms:
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 14, 2014