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Advanced Pancreatic AdenocarcinomaPhase 2NCT04524702

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

A Phase 2 study testing Gemcitabine, Hydroxychloroquine and Nab-paclitaxel in people with Advanced Pancreatic Adenocarcinoma and Metastatic Pancreatic Adenocarcinoma, run by Emory University at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Gemcitabine, Hydroxychloroquine and Nab-paclitaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
3 sitesUnited States
Study dates
14 Sep 2020to 6 Jun 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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
  • Patients with known G6PD deficiency, severe psoriasis, porphyria, macular degeneration or severe diabetic retinopathy are ineligible because of the potential for greater hydroxychloroquine (HCQ) toxicity
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardio- toxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
  • The effects of study drugs used in this study on the developing human fetus are unknown. For this reason, female of child-bearing potential (FCBP) must have a negative serum or urine pregnancy test prior to starting therapy
  • FCBP and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 1 month after completion of drug administration
  • Willingness and ability of the subject to comply with scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions
  • Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation

Who cannot join

  • 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
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  • 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

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Emory Saint Joseph's Hosptial

    Atlanta, Georgia, 30342

Other trials in United States

About this study

Official title: Phase II Trial of Paricalcitol and Hydroxychloroquine (PH) Combination With Gemcitabine and Nab-Paclitaxel in Advanced or Metastatic Pancreatic Cancer

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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:

  1. 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.

Being tested
Gemcitabine, Hydroxychloroquine, Nab-paclitaxel, Paricalcitol
Medical subject headings
Pancreatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GemcitabineDrug

    Also called dFdC, dFdCyd, Difluorodeoxycytidine

    Given IV

  • HydroxychloroquineDrug

    Given PO

  • Nab-paclitaxelDrug

    Also called ABI 007, ABI-007, Abraxane, Albumin-bound Paclitaxel

    Given IV

  • ParicalcitolDrug

    Also called Compound 49510, Zemplar

    Given IV

Study groups in NCT04524702
Study groupRoleWhat they receive
Treatment (paricalcitol, hydroxychloroquine, chemotherapy)ExperimentalBeginning 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.
Receives: Drug: Gemcitabine; Drug: Hydroxychloroquine; Drug: Nab-paclitaxel; Drug: Paricalcitol

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: At 8 weeks

Secondary outcomes (3)

  1. Incidence of Adverse Events

    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.

    Measured: 1 year

  2. Progression-free Survival

    Assessed using RECIST 1.1. Will be estimated using the Kaplan-Meier method.

    Measured: 32.5 Months

  3. Overall Survival

    Will be estimated using the Kaplan-Meier method.

    Measured: 32.5 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Aug 2020
  2. Study start14 Sep 2020
  3. Primary completion6 Jun 2023
  4. Study completion6 Jun 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04524702
Sponsor's protocol ID
STUDY00000996
Other IDs
NCI-2020-05417, Winship5079-20, P30CA138292
Status last verified
Sep 2025
First submitted
13 Aug 2020
Last updated
23 Jan 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 39730001

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Gemcitabine, Hydroxychloroquine and Nab-paclitaxel in people with Advanced Pancreatic Adenocarcinoma and Metastatic Pancreatic Adenocarcinoma, run by Emory University at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Jan 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Assessment of Tumor Response to Combination of Paricalcitol and Hydroxychloroquine With Common Front-line Therapy. (time frame: At 8 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04524702, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2026.

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