Evaluation of Clinical Safety of Combining Metformin With Anticancer Chemotherapy

Inclusion Criteria:

- Histologically or cytologically documented cancer; diagnosis of hepatocellular
carcinoma may be made by characteristic radiographic and/or AFP findings 33;

- Intended treatment with, or currently being treated by anti-cancer chemotherapy in
the adjuvant or advanced setting;

- Age 18 to 79;

- Adequate renal function (serum creatinine levels <1.5 mg/dL [males], <1.4 mg/dL
[females]). If a subject does not meet these criteria, but does have an estimated
creatinine clearance >= 60 ml/min using the Cockroft-Gault calculation, they will be
allowed. The Cockroft-Gault formula is CrCl = (140-age) x weight(kg)÷(Cr x72), where
CrCl = estimated creatinine clearance and Cr is plasma creatinine in mg/dL;

- 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;

- Must anticipate receiving at least 3 cycles (or treatment periods of at least
3-weeks) of chemotherapy;

- Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

- Current use of metformin (within 1 week of start of chemotherapy regimen to be
assessed);

- Patients with type 2 diabetes are allowed, however they will be excluded if there is
intent to use metformin for treatment of diabetes during the course of the study;

- Undergoing chemotherapy treatment concurrent with radiation therapy;

- Undergoing chemotherapy in a neoadjuvant setting prior to potentially curative
surgery;

- 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 (serum pregnancy test will be performed for all women of
child-bearing potential);

- Psychiatric illness or social situation that would limit compliance with study
requirements and/or obscure results