A Randomized Pilot/Pharmacodynamic/Genomic Study of Neoadjuvant Paricalcitol to Target the Microenvironment in Resectable Pancreatic Cancer

Study Overview
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Brief Summary
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This study is a randomized pilot/pharmacodynamic/genomic study of neoadjuvant paricalcitol to target the microenvironment in resectable pancreatic cancer to determine the effect of targeting the vitamin D metabolic program in the tumors of patients treated with one cycle of gemcitabine/abraxane with or without paricalcitol prior to surgery for resectable pancreatic cancer through an assessment of cellular and imaging markers.

Official Title
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A Randomized Pilot/Pharmacodynamic/Genomic Study of Neoadjuvant Paricalcitol to Target the Microenvironment in Resectable Pancreatic Cancer

Conditions
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Adenocarcinoma of the Pancreas

Intervention / Treatment
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* Drug: Paricalcitol
* Drug: Abraxane
* Drug: Gemcitabine


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 Eastern Cooperative Oncology Group 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 patient on the trial. Note: subjects must have: Creatinine < 2x Upper Normal Limit , Transaminases < 3x Upper Normal Limit, Neutrophils >1.5x109/L, and Platelets >100,000/mm3 Ability to provide written informed consent Exclusion Criteria Patients with hypercalcemia (blood levels greater than 11.5 mg/dL; in patients with kidney disease, blood calcium levels must be 9.5 mg/dL or lower before starting paricalcitol). Patients who are currently pregnant, planning to become pregnant, or breast-feeding. Patients who, in the opinion of the physician, would not be clinically appropriate for receipt of the therapy regimen associated with participation

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pre-operative Paricalcitol<br>Subject will receive gemcitabine/abraxane with preoperatively paricalcitol. Patients randomized to receive paricalcitol pre-operatively will begin treatment with intravenous paricalcitol at 25 μg three times weekly for one cycle beginning day 1 of therapy until the day before surgery (+/- 3 days). | Drug: Paricalcitol<br>* Dose: 25 micrograms Route: IV Frequency (within a 28 day cycle):Three times weekly for one cycle beginning day 1 of therapy until the day before surgery (+/- 3 days) (for subjects randomized to receive paricalcitol), then three times weekly for 3 cycles post-operatively (for all subjects).<br>Drug: Abraxane<br>* Dose: 125mg/m2 Route: IV infusion over 30 minutes Frequency (within a 28 day cycle): Day 1, 8, 15<br>Drug: Gemcitabine<br>* Dose: 1000mg/m2 Route: IV infusion over 30-100 minutes Frequency (within a 28 day cycle): Day 1, 8, 15<br>|
| Active Comparator: No Pre-operative Paricalcitol<br>Subject will receive gemcitabine/abraxane without paricalcitol preoperatively. | Drug: Abraxane<br>* Dose: 125mg/m2 Route: IV infusion over 30 minutes Frequency (within a 28 day cycle): Day 1, 8, 15<br>Drug: Gemcitabine<br>* Dose: 1000mg/m2 Route: IV infusion over 30-100 minutes Frequency (within a 28 day cycle): Day 1, 8, 15<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events |  | 2 years |