Paricalcitol Plus Gemcitabine and Nab-paclitaxel in Metastatic Pancreatic Cancer

Inclusion Criteria: * Histologically-confirmed pancreatic adenocarcinoma or poorly differentiated carcinoma that is metastatic to distant sites. * Other histologies such as neuroendocrine and acinar cell carcinoma are excluded. Patients with locally advanced, unresectable disease without distant metastases are excluded. * No prior chemotherapy for locally advanced or metastatic pancreatic cancer. * Patients are eligible if they received adjuvant treatment after surgical resection with single-agent gemcitabine or gemcitabine plus capecitabine or gemcitabine and nab-paclitaxel or 5-fluorouracil/leucovorin or 5-FU/leucovorin plus irinotecan and oxaliplatin that was completed \>12 months before enrollment. Similarly, adjuvant radiation +/- chemosensitization with 5-fluorouracil, capecitabine, or gemcitabine is allowed if completed \>12 months before enrollment. * Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam. See Section 11 for the evaluation of measurable disease. * Age greater than or equal to 18 years. * Patients must have completed any major surgery or open biopsy ≥4 weeks from start of treatment. * ECOG performance status ≤1 (see Appendix A) * Participants must have normal organ and marrow function as defined below: * Absolute neutrophil count ≥1,500/mcL * Platelets ≥100,000/mcL * Total bilirubin ≤1.5 × institutional upper limit of normal * AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal * Calcium (corrected for albumin) \* ≤1 × institutional upper limit of normal * Creatinine ≤1.5 × institutional upper limit of normal OR * Creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels above 1.5 × upper limit of normal. * Corrected Calcium = serum calcium (mg/dL) + 0.8 (4 - serum albumin (g/dL)) * Ability to understand and the willingness to sign a written informed consent document. * Negative pregnancy testing for women of child bearing age * The effects of Paricalcitol, Gemcitabine and nab-Paclitaxel on the developing human fetus are unknown. For this reason and because vitamin D receptor agonist agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of treatment administration Exclusion Criteria: * Prior chemotherapy or any other investigational agents for the treatment of locally advanced or metastatic pancreatic cancer * Concurrent use of any other anti-cancer therapy, including chemotherapy, targeted therapy, immunotherapy, or biological agents. * Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to paricalcitol, gemcitabine or nab-paclitaxel * Pre-existing hypercalcemia, defined as baseline serum calcium (corrected for albumin) above the institutional upper limit of normal. * At the time of trial enrollment, vitamin D containing supplements must be stopped and no vitamin D supplements can be taken while the patient is enrolled to the study due to increased risk for hypercalcemia * At the time of trial enrollment, calcium containing supplements must be stopped and no calcium supplements can be taken while the patient is enrolled to the study due to increased risk for hypercalcemia * History of symptomatic genitourinary stones (e.g. kidney stones) within the past 12 months * History of prior or current synchronous malignancy, except: * Malignancy that was treated with curative intent and for which there has been no known active disease for \>3 years prior to enrollment * Curatively treated non-melanoma skin cancer, cervical cancer in situ, or prostatic intraepithelial neoplasia, without evidence of prostate cancer * Pre-existing, clinically significant peripheral neuropathy, defined as CTCAE grade 2 or higher neurosensory or neuromotor toxicity, regardless of etiology * Regular use of thiazide diuretics (e.g. hydrochlorothiazide), which can lead to hypercalcemia. Patients must stop these diuretics prior to initiating treatment. Other anti-hypertensive medications can be substituted, as needed. * Participants receiving any medications or substances that are inhibitors or inducers of CYP450 3A enzyme(s) are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/table.aspx; medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product. \[see Appendix D\] * 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. * Participant must be able to swallow and absorb pills. * Pregnant women are excluded from this study because Paricalcitol is a vitamin D receptor agonist agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Paricalcitol, breastfeeding should be discontinued if the mother is treated with Paricalcitol. These potential risks may also apply to other agents used in this study.