Metformin Pharmacology in Human Cancers: A Proof of Principle Study

Inclusion Criteria:

* Invasive malignant solid tumor of thoracic origin (e.g., lung, esophageal, thymus, mesothelioma, chest wall, mediastinum, trachea, pleura) with the intent to treat or biopsy by surgery as standard of care. Tumor must be ≥2 centimeters (cm).
* Patients with multicentric disease are eligible. Samples from all available tumors are requested for research purposes.
* Patients with Type 2 diabetes mellitus being treated with metformin (any dose) for a clinical indication at the time of study enrollment are eligible, and will continue metformin treatment as clinically indicated during the presurgical study period. Their dose of metformin will NOT be changed.
* Patients not on metformin at the time of study entry must be willing to take metformin extended release (Glucophage® XR, 750 mg QD for 4 days, then 750 mg BID for 3-6 days) for a total of 7-10 days prior to surgery.
* Patients do not require a diagnosis of diabetes to be enrolled in the study.
* All patients must be willing to keep a drug diary indicating the dates and times of metformin administration.

Patients must meet the following clinical laboratory criteria:

* Absolute neutrophil count (ANC) greater than or equal to 1,500/mm3 and platelet count greater than or equal to 75,000/mm3.
* Total bilirubin less than or equal to 1.5x the upper limit of the normal range (ULN).
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 3x ULN.
* Estimated glomerular filtration rate (eGFR) \> 60 mL/min/1.73m2 or estimated creatinine clearance (eCrCL) \> 60 mL/min
* Ability to give informed consent.
* Patients must be willing to provide 20 milliliters (mL) of blood for research use.
* Patient must be willing to provide consent for use of archived tissue for research.

Exclusion Criteria:

* History of diabetes that is currently being treated without metformin.
* Patients who, at the time of study entry, are not taking metformin for a clinical indication, and who will need a radiographic analysis with an iodinated contrast agent during the metformin study treatment period.
* This criterion does not apply to patients taking clinically indicated metformin at the time of study entry.
* History of liver disease as defined with liver function tests (LFTs) above those in the inclusion
* Known hypersensitivity to metformin.
* History of reactive hypoglycemia.
* Active or history of lactic acidosis, metabolic acidosis, or diabetic ketoacidosis.