Metformin Hydrochloride in Treating Patients With Pancreatic Cancer That Can be Removed by Surgery

A Pharmacodynamic Study of Metformin in Patients With Resectable Pancreatic Cancer

This randomized clinical trial studies metformin hydrochloride in treating patients with pancreatic cancer that can be removed by surgery. Metformin hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To determine the effect of escalating doses of metformin (metformin hydrochloride) given pre-operatively on pancreatic cancer cell proliferation and apoptosis.

SECONDARY OBJECTIVES:

I. To assess toxicity of escalating doses of metformin given pre-operatively in patients with resectable pancreatic carcinoma.

II. To measure the effect of metformin on the expression of phosphorylated acetyl-CoA carboxylase alpha (ACC), phosphorylated mechanistic target of rapamycin (serine/threonine kinase) (mTOR), and pancreatic cancer stem cells.

OUTLINE: Patients are randomized to 1 of 3 treatment groups.

GROUP I: Patients undergo observation.

GROUP II: Patients receive metformin hydrochloride orally (PO) twice daily (BID) for at least 7 days in the absence of disease progression or unacceptable toxicity.

GROUP III: Patients receive metformin hydrochloride as in Group II.

After completion of study treatment, patients are followed up 30 days.

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed resectable pancreatic carcinoma; patients with pancreatic neuroendocrine tumors are not eligible
• Patients must be previously untreated with chemotherapy or radiation therapy
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Patients must have surgical resection of the pancreas planned, with enrollment at least 7 days prior to surgery; patients with surgery scheduled > 15 days will not be excluded
• Hemoglobin (Hg)A1C must be below 7%
• Total bilirubin less than 1.5 X institutional upper limit of normal
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 X institutional upper limit of normal
• Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
• Serum creatinine within normal institutional limits
• Alkaline phosphatase < 1.5 X institutional upper limit of normal
• Subjects must have the ability to understand and be willing to provide written informed consent

Exclusion Criteria:

• History of metformin use in the previous 3 months
• Treatment with neoadjuvant chemotherapy or radiation therapy
• History of allergic reactions attributed to metformin
• Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Metabolic acidosis, acute or chronic, including ketoacidosis
• Metastatic disease