Nivolumab, Paricalcitol, and Combination Chemotherapy Before and After Surgery for the Treatment of Resectable Pancreatic Cancer

Inclusion Criteria

• Previously untreated, apparently resectable (defined in section 4.5) adenocarcinoma of the pancreas at registration. Histologic confirmation of adenocarcinoma must be obtained before chemotherapy is initiated
• A tumor biopsy must be obtained before the initiation of treatment for characterization of the tumor subtype (epithelial versus [vs] quasi-mesenchymal [QM]) – unless the patient has usable baseline tissue obtained previously. (Note that patients who meet these inclusion criteria, and have tissue sent for analysis may have treatment initiated with chemotherapy while tissue analysis is completed.)
• Age greater than or equal to 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Standard laboratory criteria for hematologic, biochemical, and urinary indices within a range that, in the opinion of the physician, clinically supports enrollment of the subject on the trial * Note: subjects must have: creatinine =< 1.5 x upper limit of normal (ULN) AND estimated glomerular filtration Rate (eGFR) >= 50 by Cockcroft-Gault equation, neutrophils > 1.5 x 10^9/L, total bilirubin =< 1.5 x ULN (3 x ULN if due to biliary obstruction), aspartate aminotransferase (AST) =< 3 x ULN (5 x ULN if due to biliary obstruction), alanine aminotransferase (ALT) =< 3 x ULN (5 x ULN if due to biliary obstruction), and platelets > 100,000/mm^3
• Ability to provide written informed consent
• Willing and eligible to undergo paired MRI examinations

Exclusion Criteria

• Subjects with hypercalcemia (blood levels greater than 11.5 mg/dL). In subjects with creatinine clearance 50-60 mL/min, blood calcium levels must be 9.5 mg/dL or lower
• Subjects who are currently pregnant, planning to become pregnant, or breast-feeding * Females participants of child-bearing potential are required to use an effective contraception method or abstain from intercourse during treatment and for at least 5 months following the last dose * Males participants with partners of child-bearing potential are required to use an effective contraception method or abstain from intercourse during treatment and for at least 7 months following the last dose
• Subjects who, in the opinion of the physician, would not be clinically appropriate for receipt of the therapy regimen associated with participation
• Subjects with contraindications to immune checkpoint therapy, as follows: * Interstitial lung disease that is symptomatic or may interfere with the detection and management of suspected drug-related pulmonary toxicity * Prior organ allograft or allogeneic bone marrow transplantation * Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication * Active autoimmune disease, except for vitiligo, type 1 diabetes mellitus, asthma, atopic dermatitis, or endocrinopathies manageable by hormone replacement; other autoimmune conditions may be allowable at the discretion of the principal investigator * Condition requiring systemic treatment with either corticosteroids ** Systemic steroids at physiologic doses (equivalent to dose of oral prednisone 10 mg) are permitted. Steroids as anti-emetics for chemotherapy are strongly discouraged ** Intranasal, inhaled, topical, intra-articular, and ocular corticosteroids with minimal systemic absorption are permitted