This randomized pilot early phase I trial studies the potential effects of paricalcitol (a drug similar to vitamin D) on pancreatic tumors in patients who are treated with gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation. Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, gemcitabine hydrochloride, and paricalcitol work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02030860.
PRIMARY OBJECTIVES:
I. To determine the effect of targeting the vitamin D metabolic program in the tumors of patients treated with one cycle of gemcitabine (gemcitabine hydrochloride)/Abraxane (paclitaxel albumin-stabilized nanoparticle formulation) + paricalcitol prior to surgery for resectable pancreatic cancer through an assessment of cellular and imaging markers.
SECONDARY OBJECTIVES:
I. To describe the effect of gemcitabine/Abraxane + paricalcitol on tumor response to neoadjuvant chemotherapy in the primary tumor in resectable pancreatic cancer.
II. To describe in this small patient sample any effect of paricalcitol on the vitamin D-regulated pancreatic stellate cell gene expression program.
III. To determine the safety of this neoadjuvant approach by defining the adverse effects in both arms of the study.
IV. To analyze circulating markers of endothelial cell function and oxidative stress in paricalcitol-treated patients.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I:
PRE-OPERATIVE CHEMOTHERAPY: Patients receive paclitaxel albumin-stabilized nanoparticle formulation intravenously (IV) over 30 minutes and gemcitabine hydrochloride IV over 30-100 minutes on days 1, 8, and 15.
ARM II:
PRE-OPERATIVE CHEMOTHERAPY: Patients receive gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation as in Arm I and paricalcitol IV three times weekly on days 1-28.
SURGERY: Within 4-8 weeks after completion of pre-operative treatment, all patients undergo surgery.
POST-OPERATIVE CHEMOTHERAPY: Beginning within 4-8 weeks after surgery, patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15; gemcitabine hydrochloride IV over 30-100 minutes on days 1, 8, and 15; and paricalcitol IV 3 times weekly on days 1-28. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for 1 year and then annually for 2 years.
Lead OrganizationUniversity of Pennsylvania/Abramson Cancer Center
Principal InvestigatorPeter James O'Dwyer
