PHL Treatment in Pancreatic Cancer

NCT05365893 | Active Not Recruiting Early Phase 1 DMC FDA Drug

• 3 other identifiers: 20-1085GI-1741R21CA252535-01A1
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This proposal will investigate the effect of paricalcitol, hydroxychloroquine, and losartan (PHL) combination of 3 stroma-modifying drugs on pancreatic adenocarcinoma and its stroma.

Conditions

Pancreatic Ductal Adenocarcinoma

Keywords

chemo-resistant cancer

Outcome Measures

Primary Outcomes (1)

• Number of participants who experience grade 3 or greater treatment-related adverse events assessed by CTCAE v5.0

  Feasibility of administering PHL when given in the window between neoadjuvant chemo-radiotherapy and surgery. Feasibility is defined as the ability to tolerate a minimum of 4 weeks of PHL treatment without interfering with patient's planned surgery.

  4 weeks

Study Arms (2)

PHL (Paricalcitol, Hydroxychloroquine, Losartan)

EXPERIMENTAL

Paricalcitol 25 mcg IV administered M-W-F Hydroxychloroquine 600 mg PO BID Losartan 50 mg PO daily

Combination Product: Paricalcitol, Hydroxychloroquine, Losartan

Neoadjuvant therapy and surgery only (Control)

ACTIVE COMPARATOR

Control arm These patients will proceed to surgery at completion of neoadjuvant therapy.

Other: Neoadjuvant therapy and surgery only (Control)

Interventions

Paricalcitol, Hydroxychloroquine, Losartan COMBINATION_PRODUCT

Paricalcitol 25 mcg IV administered M-W-F Hydroxychloroquine 600 mg PO BID Losartan 50 mg PO daily

PHL (Paricalcitol, Hydroxychloroquine, Losartan)

Neoadjuvant therapy and surgery only (Control) OTHER

Control arm These patients will proceed to surgery at completion of neoadjuvant therapy.

Neoadjuvant therapy and surgery only (Control)

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 new diagnosed histologically or cytologically confirmed pancreatic adenocarcinoma.
• Patients must have resectable non-metastatic PDAC and anticipate receiving surgery in a minimum of 4 weeks and a maximum of 12 weeks from completing neoadjuvant chemotherapy and radiation.
• Patients are planned for a minimum of 3 months of modified FOLFIRINOX treatment followed by chemo/radiation followed by surgical resection.
• Age \> 18 years.
• ECOG performance status 0-1
• Patients must have normal organ function as defined below
• Total bilirubin within normal institutional limits
• AST/ALT (SGOT/SGPT) \< 5 times institutional normal limits
• Creatinine within normal institutional limits OR
• Creatinine clearance \> 30 Ml/min/1.73 m2 for patients with creatinine levels above institutional normal
• Women of childbearing potential must be non-pregnant (negative pregnancy test within 72 hours prior to registration). Postmenopausal woman must have been amenorrhoeic and nonlactating for at least 12 months to be considered of non-childbearing potential. Men and women of child bearing potential must be willing to exercise an effective form of birth control (abstinence/contraception) while on study and for 3 months after therapy is completed.
• Ability to understand and willingness to sign a written informed consent and HIPAA consent document

You may not qualify if:

• Tumors of acinar or adenocarcinoma histology
• Patients may not be receiving any other investigational agents
• Patients currently receiving hydroxychloroquine or an angiotensin II receptor blocker
• Patients with radiological or cytologically confirmed metastatic or unresectable disease
• Pregnant or breast feeding. Refer to section 4.4 for further detail.
• Patients must have resectable non-metastatic PDAC and anticipate receiving surgery in a minimum of 4 weeks and a maximum of 12 weeks from completing neoadjuvant chemotherapy and chemoradiation.
• Patients completed a minimum of 3 months of modified FOLFIRINOX treatment followed by chemoradiation prior to study enrollment and plans for surgical resection.
• Ability to understand and willingness to sign a written informed consent and HIPAA consent document
• Patients who have residual grade 3 or higher adverse events from prior chemotherapy or chemoradiotherapy for pancreatic cancer
• Concomitant use of an ACE inhibitor or ARB, vitamin D, or hydroxychloroquine. Patient may elect to stop Vitamin D supplement and will be allowed to enroll on the study.
• Patients cannot have a history of retinopathy, macular degeneration or other severe ocular issues, baseline hypotension (systolic blood pressure lower than 100 mmHg on two separate readings obtained on two separate days), or history of hypercalcemia requiring treatment
• Patients with known disorders precluding use of any of the study drugs including a history of angioedema, hypotension, or renal disease (CrCl \< 30mL/min).
• History of allergic reactions attributed to compound of similar chemical or biologic composition to the agent(s) used in this study
• Patients receiving any medications or substances that significantly interact with PHL are ineligible (specified in section 5.2).
• A marked baseline prolongation of QT/QTc interval

Sponsors & Collaborators

• Fox Chase Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

MeSH Terms

Interventions

paricalcitol; Hydroxychloroquine; Losartan; Neoadjuvant Therapy

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Tetrazoles; Combined Modality Therapy; Therapeutics

Study Officials

• Sanjay Reddy, MD, FACS

  Fox Chase Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 20 patients diagnosed with resectable pancreatic cancer will be consented for blood and tissue prior to starting neoadjuvant therapy. 10 patients will be assigned to the experimental (PHL) arm (Arm A). Treatment arm; N=10 (Consented for PHL the time of neoadjuvant therapy completion): Experimental therapy 4-8 weeks pre-op: Paricalcitol 25 mcg IV administered M-W-F Hydroxychloroquine 600 mg PO BID Losartan 50 mg PO daily Control arm (Arm B); N=10 These patients have already signed consent for blood and tissue- will proceed to surgery at completion of neoadjuvant therapy.

Study Record Dates

• First Submitted: November 4, 2021
• First Posted: May 9, 2022
• Study Start: October 20, 2021
• Primary Completion: December 18, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 22, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)