A Pilot Study of Perioperative Nivolumab and Paricalcitol to Target the Micoenvironment in Resectable Pancreatic Cancer

Study Overview
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Brief Summary
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The main purpose of this study is to look at the potential effects of paricalcitol (a drug similar to vitamin D) and nivolumab on pancreatic tumors in patients who are treated with gemcitabine and abraxane. The study will also look at the safety of including paricalcitol and nivolumab as part of the gemcitabine and abraxane chemotherapeutic regimen.

Official Title
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A Pilot Study of Perioperative Nivolumab and Paricalcitol to Target the Micoenvironment in Resectable Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: Nivolumab
* Drug: Nab-Paclitaxel
* Drug: Gemcitabine
* Drug: Paricalcitol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previously untreated, apparently resectable adenocarcinoma of the pancreas at registration. Age greater than or equal to 18 years 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. a. Note: subjects must have: Creatinine < 2xULN, Neutrophils >1.5x109/L, total bilirubin < 3xULN, AST <5xULN, ALT <5xULN, and Platelets >100,000/mm3 Ability to provide written informed consent Exclusion Criteria: Subjects with hypercalcemia (blood levels greater than 11.5 mg/dL). In subjects creatinine clearance <60mL/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 (see Appendix A) 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 (see Appendix A) or abstain from intercourse during treatment and for at least 5 months following the last dose 3. Subjects who, in the opinion of the physician, would not be clinically appropriate for receipt of the therapy regimen associated with participation 4. 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 (see section 5.1.3) Intranasal, inhaled, topical, intra-articular, and ocular corticosteroids with minimal systemic absorption are permitted

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br> | Drug: Nivolumab<br>* Before Surgery Wks 1 &3, After Surgery Wks 1 &3<br>Drug: Nab-Paclitaxel<br>* Wks 1,2,3 before surgery and Wks 1, 2,3 after surgery<br>Drug: Gemcitabine<br>* Wks 1,2,3 before surgery and Wks 1,2,3 after surgery<br>Drug: Paricalcitol<br>* Wks 1,2,3, 4 before surgery and Wks 1,2,3 after surgery<br>|
| Experimental: Arm B<br> | Drug: Nivolumab<br>* Before Surgery Wks 1 &3, After Surgery Wks 1 &3<br>Drug: Nab-Paclitaxel<br>* Wks 1,2,3 before surgery and Wks 1, 2,3 after surgery<br>Drug: Gemcitabine<br>* Wks 1,2,3 before surgery and Wks 1,2,3 after surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numer of Adverse Events |  | 18 months |