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
(gemcitabine hydrochloride), Abraxane (paclitaxel albumin-stabilized nanoparticle
formulation), metformin (metformin hydrochloride), 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. Courses 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