Trial of Metformin for Colorectal Cancer Risk Reduction for History of Colorectal Adenomas and Elevated BMI
Condition: Adenomatous Polyp; Colorectal Cancer; Obesity
MeSH terms: Colorectal Neoplasms; Adenoma; Adenomatous Polyps
Intervention: metformin hydrochloride
Intervention MeSH terms: Metformin
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 45.0
Sex: All
Minimum age: 35 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to find out whether METFORMIN decreases protein markers in
      colorectal tissue. This is a phase IIA study of the pharmacodynamics, safety and tolerability
      of Metformin in decreasing colorectal mucosa in patients with a history of colorectal
      adenomas in the past 3 years and a BMI >= 30, with decimals rounded to the nearest whole
      integer. Metformin as a potential chemopreventive agent for inhibition of the relevant
      molecular pathways involved in human colorectal carcinogenesis.
    

Eligibility criteria:

        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