Impact of Pretreatment With Metformin on Colorectal Cancer Stem Cells (CCSC) and Related Pharmacodynamic Markers

Inclusion Criteria:

• Histologically documented colorectal cancer
• Intent to undergo disease resection or biopsy at least 7days from the treatment start date (allowing for a minimum of 5 days of treatment plus 2 days break)
• Medically fit for resection of their primary tumor or for biopsy
• Age 18-79 years
• Adequate renal function (serum creatinine levels <1.5 mg/dL [males], <1.4 mg/dL [females] or estimated creatinine clearance >= 60 ml/min)
• Adequate hepatic parameters, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 x upper limit of normal (ULN), total bilirubin ≤ 1.5 x ULN, and alkaline phosphatase levels ≤ 2.5 x ULN
• Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

• Intent to administer neoadjuvant chemotherapy or radiation therapy prior to the surgery or biopsy;
• Intent to perform surgery or biopsy within 7 days of study treatment start;
• Any situation where participation in this trial would alter, or cause significant risk of altering the ability or timing of a subject to undergo resection of their tumor
• Current use of metformin (within the past month);
• Blood glucose using point of care test < 70mg/dl;
• Renal disease or renal dysfunction not meeting inclusion criteria;
• Significant medical conditions such as cardiovascular collapse (shock), acute myocardial infarction, septicemia, acute or chronic metabolic acidosis
• History of, or states associated with, lactic acidosis such as shock or pulmonary insufficiency, alcoholism (acute or chronic), conditions associated with hypoxemia and pancreatitis
• Severe dehydration
• Clinical or laboratory evidence of hepatic disease
• Congestive heart failure requiring pharmacologic treatment, or unstable or acute congestive heart failure
• Known hypersensitivity to metformin hydrochloride
• Pregnant or lactating women
• Psychiatric illness or social situation that would limit compliance with study requirements and/or obscure results