Paricalcitol and Hydroxychloroquine in Combination With Gemcitabine and Nab-Paclitaxel for Advanced Pancreatic Cancer

Brief summary public domain (ClinicalTrials.gov)

This phase II trial investigates how well paricalcitol and hydroxychloroquine work when combined with gemcitabine and nab-paclitaxel in treating patients with pancreatic cancer that has spread to other places in the body (advanced or metastatic). Paricalcitol (a form of vitamin D) works by blocking a signal in the cancer cells that leads to growth and spreading of the tumor. Hydroxychloroquine (an autophagy inhibitor) enhances the activity of standard chemotherapy on cancer cells and prevent them to utilize energy to grow. Chemotherapy drugs, such as gemcitabine and nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving paricalcitol and hydroxychloroquine together with standard chemotherapy (gemcitabine and nab-paclitaxel) may work better in treating patients with pancreatic cancer compared to either paricalcitol or hydroxychloroquine alone.

Detailed description public domain (ClinicalTrials.gov)

PRIMARY OBJECTIVE: I. To evaluate the anti-tumor activity of the combination of paricalcitol plus hydroxychloroquine (PH) when added to gemcitabine and nab-paclitaxel treatment by assessing the overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. SECONDARY OBJECTIVES: I. To evaluate the safety and tolerability of the combination of paricalcitol plus hydroxychloroquine (PH) when added to gemcitabine and nab-paclitaxel treatment in patients with advanced pancreatic cancer. II. To evaluate the anti-tumor activity of the combination of paricalcitol plus hydroxychloroquine (PH) when added to gemcitabine and nab-paclitaxel treatment by assessing progression-free survival (PFS) and overall survival (OS). TERTIARY/EXPLORATORY OBJECTIVES: I. Evaluate the effects of PH on cancer-associated fibroblasts (CAF) and immune cells using mass cytometry (CyTOF) to characterize the presence and distribution of these cells. II. Multiplex immunohistochemistry (IHC) to evaluate these pathways including TGF-beta1, TGF-beta1 RII, SMAD4, LC3 in addition to markers of fibrosis (collagen) and tumor (cytokeratin). OUTLINE: Beginning day -14, patients receive paricalcitol intravenously (IV) three times weekly and hydroxychloroquine orally (PO) twice daily (BID). Patients also receive gemcitabine IV over 30 minutes and nab-paclitaxel IV over 30 minutes on days 1, 8, 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 28 days and every 12 weeks thereafter.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Assessment of Tumor Response to Combination of Paricalcitol and Hydroxychloroquine With Common Front-line Therapy. [At 8 weeks]. Number, percentage of participants (90% Confidence Interval). Treatment (Paricalcitol, Hydroxychloroquine, Chemotherapy) (n=7): 43 (10 to 82).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Incidence of Adverse Events [1 year]. Count Of Participants, Participants. Action taken after AE, No action taken: Treatment (Paricalcitol, Hydroxychloroquine, Chemotherapy) (n=9): 7. Action taken after AE, dose interrupted: Treatment (Paricalcitol, Hydroxychloroquine, Chemotherapy) (n=9): 2. Action taken after AE, dose decreased: Treatment (Paricalcitol, Hydroxychloroquine, Chemotherapy) (n=9): 0. Action taken after AE, discontinued: Treatment (Paricalcitol, Hydroxychloroquine, Chemotherapy) (n=9): 0.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Progression-free Survival [32.5 Months]. Median, months (95% Confidence Interval). Treatment (Paricalcitol, Hydroxychloroquine, Chemotherapy) (n=10): 6 (1.4 to 6.7).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Overall Survival [32.5 Months]. Median, Months (95% Confidence Interval). Treatment (Paricalcitol, Hydroxychloroquine, Chemotherapy) (n=7): 6.8 (1.8 to 9.9).