Principal Investigator decided to close the study early.

The overall purpose of this research is to evaluate the safety and side effects of zoledronic acid (also known as Zometa) in patients before they have surgery to remove the cancer.

Cancer of the pancreas carries an ominous prognosis. The five-year overall survival rate of this malignancy is less than 5%. Chemotherapy with gemcitabine carries a response rate of approximately 25%. Resection offers the only potential for cure; however, even with resection, the great majority of patients will die with metastatic disease. Substantial improvements are needed in the treatment of this malignancy.

Patients with this disease process have clearly developed a tolerance to their pancreatic tumor. This is evidenced by an increased number and activity immunosuppressive cells including MDSC and Treg in patients with pancreas cancer. An intervention that inhibits this population of MDSC and Treg may be highly useful in the treatment of this disease process.

A novel treatment of pancreas cancer, in this setting, would be to deplete circulating and tumor-associated immunosuppressive cells prior to resection. This would facilitate the host to mount a greater immune response against the tumor. The eventual goal would be to combine neoadjuvant zoledronic acid with gemcitabine, another agent which synergizes with zoledronic acid to target MDSC. When combined with current adjuvant chemoradiation, the use of zoledronic acid in the neoadjuvant and adjuvant setting, it is hoped that the patient could mount a greater immune response leading to increased overall survival through the prevention of local disease and distant metastasis.

Inclusion Criteria:

• Patient must have a newly diagnosed, histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma. The histological slides or blocks must be available for review.
• Patient must have resectable disease and be a candidate for surgical treatment.
• Recent CT scan demonstrating pancreatic tumor, no evidence of distant disease, and no contraindication to resection.
• Patients must be ≥ 18 years old.
• Performance Status: Karnofsky Performance Status (KPS) ≥ 70
• Life Expectancy > 12 weeks.
• No previous history of chemotherapy for pancreas cancer prior to the start of protocol treatment.
• Patients must have recovered from uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia.
• Patients must have adequate bone marrow function defined as an absolute neutrophil count >1,500/mm3, platelet count >100,000/mm3 and hemoglobin >10 g/dl.
• Patients must have normal renal function defined as serum creatinine ≤ 1.3 mg/dl or creatinine clearance ≥ 90 ml/min/1.73 m2 with a serum creatinine > 1.3 mg/dl.
• Patients must have adequate hepatic function with total bilirubin < 5.0 mg/dl and AST ≤ 3x the institutional normal value.
• Patient must have no prior or current active autoimmune disease requiring management with immunosuppression. This includes inflammatory bowel disease, systemic vasculitis, scleroderma, psoriasis, hemolytic anemia, immune-mediated thrombocytopenia, rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, sarcoidosis or other rheumatologic disease. Asthma and chronic obstructive pulmonary disease that does not require daily systemic corticosteroids is acceptable.
• The patient with previous history of malignancy is eligible for this study only if the patient meets the following criteria for cancer survivor: (i) patient has undergone potentially curative therapy for all prior malignancies; (ii) the patient has been considered disease free for at least 5 years; (iii) adequately treated non-melanomatous skin cancer.
• For all sexually active patients, the use of adequate barrier contraception (hormonal or barrier method of birth control) will be required during therapy, prior to study entry and for the duration of study participation. Non-pregnant status will be determined in all women of childbearing potential.
• After being informed of the treatment involved, patients (or their legally authorized representative) must given written consent.

Exclusion Criteria:

• Patient is currently receiving other investigational agents.
• Pregnant and nursing women patients are not eligible.
• Patients known to be HIV positive are ineligible because of the potential inability to modulate immune responses (patient self-report).
• Patients treated with any bisphosphonate-based therapeutic for any indication, during the previous year.
• Patients with recent (within 6 weeks) or planned dental or jaw surgery dental or jaw surgery (e.g. extraction, implants).
• Current active dental problems including infection of the teeth or jawbone (maxilla or mandibular); dental or fixture trauma, or a current or prior diagnosis of osteonecrosis of the jaw (ONJ), of exposed bone in the mouth, or of slow healing after dental procedures.
• Patients with a history of aspirin sensitive asthma.