Effect of Metformin on Biomarkers of Colorectal Tumor Cell Growth

Inclusion Criteria:

• Male or female, all races and ethnicities are eligible
• Age equal to or greater than 18 years of age
• All subjects should have a pathological/histological diagnosis of colorectal cancer.
• Clinical diagnosis of stage I, II, III or IV colon cancer or stage I, II, III or IV rectal cancer; cancer may be primary including a secondary primary
• Candidate for elective surgery(for removal of primary) or endoscopic biopsy
• ECOG Performance status of 0 - 2
• Adequate renal, liver, and bone marrow function
• Hb: (adequate for surgical intervention, with transfusion if necessary)
• WBC: (normal range)
• Platelets: (180K/cmm)
• LFTs: Normal bilirubin (< 2.0mg/dL), AST/ALT (2xULN)
• Renal function: normal creatinine
• Subjects must have signed informed consent
• Female subjects must either not be of child-bearing potential or must have a negative urine pregnancy test within 7 days of beginning the drug or placebo treatment. Subjects are considered not of child-bearing potential if they are surgically sterile or they are postmenopausal for greater than 12 months.

Exclusion Criteria:

• Previously diagnosed with diabetes mellitus Type 1 or Type 2.
• Currently taking biguanides, sulfonylurea drugs, thiazolidinediones, insulin, or mTOR inhibitors or having taken any of these medications during the 12 weeks prior to study participation.
• Currently taking any non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin and unable to stop such medications due to a present medical condition.
• Clinical symptoms of gastrointestinal obstruction or bleeding and consideration for immediate surgery or immediate neoadjuvant chemoradiation.
• Familial Adenomatous Polyposis (FAP), hereditary non-polyposis colorectal cancer (HNPCC), Putz-Jeghers disease, ulcerative colitis, or Crohn's disease.
• Pregnant or lactating.
• History of lactic or other metabolic acidosis.
• Known hypersensitivity to Metformin.
• Uncontrolled infectious disease.
• History of Positivity for human immunodeficiency virus (HIV).
• History of congestive heart failure requiring pharmacologic treatment.
• History of excessive alcohol abuse, defined by a habitual intake of more than three drinks daily.
• Previous or concurrent malignancies, except non-melanoma skin cancers, unless curatively treated and with no evidence of recurrence for > 5 years, with the exception of prior CRC which has been treated and the patient has been in remission and the current primary tumor is a second CRC.
• Unable to swallow and retain oral medication.
• Mal-absorption syndrome, disease affecting gastrointestinal function, or previous resection of the stomach or small bowel.
• Current use of medications for weight loss.
• Currently taking cimetidine, thiazide diuretics or cephalexin. If a patient needs some of these agents, alternative agents should be substituted.
• If the physician feels that the candidate is not suitable for the study, he/she will be excluded.