A Phase IIa Trial of Metformin for Colorectal Cancer Risk Reduction Among Patients With a History of Colorectal Adenomas and Elevated Body Mass Index

Inclusion Criteria:

- History of prior colorectal adenomas within the past 3 years; only patients who have
had adenomas endoscopically removed are eligible; documentation of colorectal
adenomas must be determined via review of pathology reports

- Body mass index (BMI) ≥ 30; rounded to the nearest whole integer

- Eastern Cooperative Oncology Group (ECOG) performance status 0-1

- Leukocytes ≥ 3,000/μL (≥ 2,500/μL for African-American participants)

- Absolute neutrophil count ≥ 1,500/μL (≥ 1,000/μL for African-American participants)

- Platelets ≥ 100,000/μL

- Total bilirubin within normal institutional limits

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
≤ 1.5 X institutional upper limit of normal (ULN)

- Creatinine within normal institutional limits

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and
for the duration of study participation

- A serum pregnancy test must be performed and be negative in all women of childbearing
potential within 2 weeks prior to starting treatment

- Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

- History of colorectal cancer or other cancer(s) (except for non-melanoma skin
cancers) within the last 3 years

- Family history of hereditary intestinal polyp disorder (e.g., familial adenomatous
polyposis [FAP], hereditary non-polyposis colorectal cancer [HNPCC], Putz-Jegher's
disease)

- Participants with diabetes

- History of vitamin B12 deficiency or megaloblastic anemia

- History of lactic acidosis

- Diet or other medications for weight loss

- Diseases associated with weight loss: anorexia, bulimia, or nausea

- Treatment with medications that may increase metformin levels: cationic drugs, e.g.,
digoxin, amiloride, procainamide, trimethoprim, vancomycin, triamterene, and morphine

- Treatment with other oral hypoglycemic agents

- Participants who have undergone full bowel resection, ablation or other local
therapies

- Participants may not be receiving any other investigational agents

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to metformin

- Participants with human immunodeficiency virus (HIV), cirrhosis of any cause, NASH
(nonalcoholic steatohepatitis), or hepatitis (auto-immune or infectious)

- Kidney disease or renal insufficiency (defined as serum creatinine > 1.4 mg/dL for
females or > 1.5 mg/dL for males)

- Metabolic acidosis, acute or chronic, including ketoacidosis

- Uncontrolled intercurrent illness including, but not limited to:

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Psychiatric illness/social situations that would limit compliance with study
requirements

- Renal failure

- Hepatic failure

- Sepsis

- Hypoxia

- Pregnant or breastfeeding women are excluded

- Participants anticipating elective surgery during the study period

- Contraindication to colonoscopy/flexible sigmoidoscopy

- Participants may not be using metformin, cimetidine (Tagament) furosemide (Lasix),
nifedipine (Cardizem), Ranitidine (Zinetac or Zantac), digoxin (Lanoxin), Quinidine
or any other drug contraindicated for use with metformin

- Chronic alcohol use or a history of alcohol abuse

- Participants with any medical psychosocial condition that, in the opinion of the
investigator, could jeopardize participation in and compliance with the study
criteria

- Participants that regularly use aspirin (ASA), nonsteroidal anti-inflammatory drugs
(NSAIDs), calcium, and cyclooxygenase (Cox)-2 inhibitors are not eligible for
enrollment; however, patients that use aspirin 81 mg daily, or aspirin 325 mg,
NSAIDs, calcium, or Cox-2 inhibitors at a frequency < 10 times per month are eligible