Metformin is a drug that is normally used to treat people with diabetes. New research has discovered that metformin may also kill cancer stem cells. These cancer stem cells make up only a small portion of a cancer, but may be responsible for resistance to chemotherapy or for causing recurrence of the cancer. Future studies are envisioned to that test the efficacy of administering metformin with chemotherapy. The purpose of this study is to assess the safety of administering metformin in combination with chemotherapy. Since chemotherapy and cancer itself both cause adverse events by themselves, this study is designed to have a run-in stage as well as a subsequent randomization to metformin or no metformin. The primary endpoint will compare the rate of dose-limiting toxicities between these two arms. After a period of 3 weeks for the primary endpoint comparison, all patients will receive metformin.

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