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

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