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

NCT04524702 | Completed Phase 2 Results DMC FDA Drug

• 4 other identifiers: STUDY00000996NCI-2020-05417Winship5079-20P30CA138292
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Metastatic Pancreatic Adenocarcinoma; Stage IV Pancreatic Cancer AJCC v8; Advanced Pancreatic Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Assessment of Tumor Response to Combination of Paricalcitol and Hydroxychloroquine With Common Front-line Therapy.

  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 RECIST 1.1. ORR is defined as the percentage of people in the trial who have partial response (PR) or complete response (CR). The Response rate will be estimated with Clopper-Pearson with a 90% exact confidence interval.

  At 8 weeks

Secondary Outcomes (3)

• Incidence of Adverse Events

  1 year

• Progression-free Survival

  32.5 Months

• Overall Survival

  32.5 Months

Other Outcomes (1)

• Percentage Change in Circulating Pancreatic Ductal Adenocarcinoma Cells

  blood collection was done at baseline (day -7), cycle 2 day 1.

Study Arms (1)

Treatment (paricalcitol, hydroxychloroquine, chemotherapy)

EXPERIMENTAL

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.

Drug: Gemcitabine; Drug: Hydroxychloroquine; Drug: Nab-paclitaxel; Drug: Paricalcitol

Interventions

Nab-paclitaxel DRUG

Given IV

Also known as: ABI 007, ABI-007, Abraxane, Albumin-bound Paclitaxel, Albumin-Stabilized Nanoparticle Paclitaxel, Nanoparticle Albumin-bound Paclitaxel, Nanoparticle Paclitaxel, Paclitaxel Albumin, paclitaxel albumin-stabilized nanoparticle formulation, Protein-bound Paclitaxel

Treatment (paricalcitol, hydroxychloroquine, chemotherapy)

Paricalcitol DRUG

Given IV

Also known as: Compound 49510, Zemplar

Treatment (paricalcitol, hydroxychloroquine, chemotherapy)

Gemcitabine DRUG

Given IV

Also known as: dFdC, dFdCyd, Difluorodeoxycytidine

Treatment (paricalcitol, hydroxychloroquine, chemotherapy)

Hydroxychloroquine DRUG

Given PO

Treatment (paricalcitol, hydroxychloroquine, chemotherapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed advanced or metastatic adenocarcinoma of the pancreas (stage IV)
• Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1 as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded as \>= 10 mm (\>= 1 cm) on computed tomography (CT) scan, magnetic resonance imaging (MRI)
• Patients may have had prior neoadjuvant or adjuvant treatment for pancreatic cancer. The last dose of chemotherapy must have been 12 months prior to study entry. No prior systemic therapy for metastatic disease
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Hemoglobin \>= 9.0 g/dl (no transfusions allowed within 7 days of cycle 1 day 1 to meet entry criteria) (within 28 days of cycle 1 day 1)
• Absolute neutrophil count (ANC) \>= 1,500/mcL (after at least 7 days without growth factor support or transfusion) (within 28 days of cycle 1 day 1)
• Platelets \>= 100,000/mcL (no transfusions allowed within 7 days of cycle 1 day 1 to meet entry criteria) (within 28 days of cycle 1 day 1)
• International normalized ratio (INR) =\< 1.5 (within 28 days of cycle 1 day 1)
• Partial thromboplastin time (PTT) \< 1.5 x upper limits of normal (ULN) (within 28 days of cycle 1 day 1)
• Total bilirubin =\< 1.5 times the institutional upper limit of normal (ULN) (within 28 days of cycle 1 day 1)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 5.0 times the ULN (within 28 days of cycle 1 day 1)
• Serum creatinine =\< 1.5× ULN or creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels \> 1.5 x ULN. Creatinine clearance should be calculated per institutional standard (within 28 days of cycle 1 day 1)
• Calcium (corrected for albumin) =\< 1 x institutional upper limit of normal (within 28 days of cycle 1 day 1)
• Patients with prior radiotherapy are acceptable. It must be at least 21 days since administration of radiation therapy and all signs of toxicity must have abated
• Patient must have a primary or metastatic non-bone site that is amenable to safe biopsy. Bone only lesions are not suitable for biopsy

You may not qualify if:

• Prior chemotherapy or any other investigational agents for the treatment of metastatic pancreatic cancer
• Concurrent use of any other anti-cancer therapy, including chemotherapy, targeted therapy, immunotherapy, or biological agents
• History of use of HCQ (aminoquinolines) or paricalcitol in the 6 months prior to study entry
• Pre-existing hypercalcemia, defined as baseline serum calcium (corrected for albumin) above the institutional upper limit of normal
• After signing consent, vitamin D or calcium containing supplements must be stopped and no vitamin D or calcium supplements can be taken while the patient is enrolled to the study due to increased risk for hypercalcemia
• Pre-existing, clinically significant peripheral neuropathy, defined as Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or higher neurosensory or neuro-motor toxicity, regardless of etiology
• Participants with uncontrolled brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
• Current use of medications that prolong QT interval unless approved by principal investigator (PI) or substances that are strong inhibitors or inducers of CYP450 3A enzyme(s)- unless approved by PI
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients with known G6PD deficiency, severe psoriasis, porphyria, macular degeneration or severe diabetic retinopathy are ineligible because of the potential for greater HCQ toxicity
• Pregnant women are excluded from this study because the use of agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with study drugs, breastfeeding should be discontinued
• Participant must be able to swallow and absorb pills

Sponsors & Collaborators

• Emory University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Emory Saint Joseph's Hosptial

Atlanta, Georgia, 30342, United States

Location

Related Publications (1)

• Nagaraju GP, Saddala MS, Foote JB, Khaliq AM, Masood A, Golivi Y, Bandi DSR, Sarvesh S, Reddy SP, Switchenko J, Carstens JL, Akce M, Herting C, Alese OB, Yoon KJ, Manne U, Bhasin MK, Lesinski GB, Sukhatme VP, El-Rayes BF. Mechanism of enhancing chemotherapy efficacy in pancreatic ductal adenocarcinoma with paricalcitol and hydroxychloroquine. Cell Rep Med. 2025 Jan 21;6(1):101881. doi: 10.1016/j.xcrm.2024.101881. Epub 2024 Dec 26.

  PMID: 39730001 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Gemcitabine; Hydroxychloroquine; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Taxes; paricalcitol

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Economics; Health Care Economics and Organizations

Results Point of Contact

• Title: Dr. Olatunji Alese
• Organization: Emory University

olatunji.alese@emory.edu

4047781900

Study Officials

• Olatunji B. Alese, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 13, 2020
• First Posted: August 24, 2020
• Study Start: September 14, 2020
• Primary Completion: June 6, 2023
• Study Completion: June 6, 2023
• Last Updated: January 23, 2026
• Results First Posted: January 23, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)