Gemcitabine Hydrochloride, Paclitaxel Albumin-Stabilized Nanoparticle Formulation, Metformin Hydrochloride, and a Standardized Dietary Supplement in Treating Patients With Pancreatic Cancer That Cannot be Removed by Surgery

PRIMARY OBJECTIVES:

I. To assess the compliance, toxicity and feasibility of administering gemcitabine hydrochloride (gemcitabine), nab-paclitaxel (abraxane), metformin hydrochloride (metformin), and the dietary supplement (DS).

SECONDARY OBJECTIVES:

I. To assess the response rate associated with this combination therapy in pancreatic cancer patients.

II. To assess the progression-free survival and overall survival of all patients who start protocol therapy, and describe the outcomes based on measures of compliance during the lead-in week, and compliance with supplement during chemotherapy.

III. To collect and analyze peripheral blood and pre-treatment biopsy samples for an exploratory analysis of biological correlatives.

IV. To assess quality of life utilizing the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire.

OUTLINE:

Patients receive gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation intravenously (IV) on days 1, 8, and 15. Patients also receive metformin hydrochloride orally (PO) twice daily (BID) starting day -6 and dietary supplement PO BID starting day -3. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months.

Inclusion criteria

• Patients must have a histologic diagnosis of pancreatic adenocarcinoma
• Patient must have unresectable disease
• Patients must not have received prior chemotherapy except for the following circumstances; gemcitabine and capecitabine chemotherapy given in the adjuvant setting is allowed if the recurrence is greater than 6 months from the completion of chemotherapy; radiation sensitizing doses of 5-fluororuracil or capecitabine are allowed as part of adjuvant treatment and recurrence must be documented greater than 6 months from the completion of adjuvant therapy
• Computed tomography (CT) or magnetic resonance imaging (MRI) scan must be obtained within 4 weeks prior to study entry
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Absolute neutrophil count > 1,500/mcl
• Platelet count > 100,000/mcl
• Creatinine < 1.4 mg/dl and/or a measured creatinine clearance > 60 cc/min
• Bilirubin < 1.4 mg/dl
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST) no greater than 3.0 times the upper limit of normal
• Patients currently being treated for severe infections or who are recovering from major surgery or other intercurrent illnesses are ineligible until recovery is deemed complete by the investigator
• Patients must not be pregnant or nursing; women and men of reproductive potential must have agreed to use an effective contraceptive method
• All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
• Patients must be able to swallow pills and must not have malabsorption problems or ongoing nausea and vomiting that would affect oral treatment
• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years
• Patients currently taking metformin will be eligible
• Patients allergic to eggs are not eligible
• Patients taking additional dietary/herbal supplements (excluding Senekot) outside of this protocol and refusing to stop are not eligible
• Patients requiring warfarin are not eligible