Randomized Clinical Trial Evaluating the 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