Paricalcitol and Hydroxychloroquine in Combination With Gemcitabine and Nab-Paclitaxel for Advanced Pancreatic Cancer
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|ClinicalTrials.gov Identifier: NCT04524702|
Recruitment Status : Recruiting
First Posted : August 24, 2020
Last Update Posted : March 15, 2022
|Condition or disease||Intervention/treatment||Phase|
|Advanced Pancreatic Adenocarcinoma Metastatic Pancreatic Adenocarcinoma Stage IV Pancreatic Cancer AJCC v8||Drug: Gemcitabine Drug: Hydroxychloroquine Drug: Nab-paclitaxel Drug: Paricalcitol||Phase 2|
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.
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).
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).
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||21 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Trial of Paricalcitol and Hydroxychloroquine (PH) Combination With Gemcitabine and Nab-Paclitaxel in Advanced or Metastatic Pancreatic Cancer|
|Actual Study Start Date :||September 14, 2020|
|Estimated Primary Completion Date :||August 14, 2023|
|Estimated Study Completion Date :||August 14, 2023|
Experimental: Treatment (paricalcitol, hydroxychloroquine, chemotherapy)
Beginning day -14, patients receive paricalcitol IV three times weekly and hydroxychloroquine PO 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.
- Change from baseline tumor size as measured by cross sectional imaging at 8 weeks.(every 8 weeks) [ Time Frame: From date of study entry until date of first documented progression or death from any cause whichever comes first up to 100 months. ]Assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Tumor measurements will be performed every 8 weeks. Response rate will be estimated, and a 90% exact confidence interval will be reported using the Clopper-Pearson method.
- Incidence of adverse events [ Time Frame: Up to 28 days post treatment from study start ]Toxicities will be presented as worst toxicity per patient and will be reported as percent toxicity. The number of subjects with skipped doses, dose delays and dose reductions as well as major reasons for dose modifications will be summarized. Adverse events will be classified using MedDRA System Organ Classes and Preferred Terms. Furthermore, serious adverse events (SAEs), adverse events (AEs) with a severity grade of 3 or above using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, AEs deemed related to study drug, AEs leading to discontinuation of study drug, and AEs leading to death will also be summarized in preferred term by system organ class and listed on an individual subject basis.
- Progression-free survival [ Time Frame: Up to 3 years from study start ]Assessed using RECIST 1.1. Will be estimated using the Kaplan-Meier method.
- Overall survival [ Time Frame: Up to 3 years from study start ]Will be estimated using the Kaplan-Meier method.
- Changes in selected biomarkers in tumor microenvironment and circulation [ Time Frame: From date of study start until date of first documented progression assessed up to 100 months. ]Will evaluate changes in selected biomarkers in tumor microenvironment and circulation before and after treatment with PH when added to gemcitabine and nab-paclitaxel treatment and their relationship.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04524702
|Contact: Olatunji B. Alese, MDfirstname.lastname@example.org|
|Contact: Walid Shaib, MDemail@example.com|
|United States, Georgia|
|Emory University Hospital Midtown||Recruiting|
|Atlanta, Georgia, United States, 30308|
|Contact: Allyson Anderson 404-251-2854 firstname.lastname@example.org|
|Emory University Hospital/Winship Cancer Institute||Recruiting|
|Atlanta, Georgia, United States, 30322|
|Contact: Erin Davis 404-778-1805 email@example.com|
|Principal Investigator: Olatunji B. Alese, MD|
|Emory Saint Joseph's Hosptial||Recruiting|
|Atlanta, Georgia, United States, 30342|
|Contact: Malendie Gaines 678-843-5911 firstname.lastname@example.org|
|Principal Investigator:||Olatunji B. Alese, MD||Emory University|