Trial of Metformin for Colorectal Cancer Risk Reduction for History of Colorectal Adenomas and Elevated BMI

• Status: Completed
• Trial end date: 2014-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Metformin

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