Hydroxychloroquine to Increase Tumor Suppressor PAR-4 Levels in Oligometastatic Prostate Cancer

NCT04011410 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 50146 - MCC-19-GU-72
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Treatment of recurrent oligometastatic prostate cancer may be enhanced by the addition of Hydroxychloroquine to the current treatment regimens. Potential benefits of Hydroxychloroquine include delayed disease progression and delayed initiation of androgen deprivation therapy (ADT), thus lessening morbidity, distressing side effects, and improving functioning and quality of life in men with recurrent prostate cancer. Building on prior research at Markey, patients recently diagnosed with recurrent oligometastatic prostate cancer will be approached about participating in this study. Per standard of care, these patients undergo either surgery or radiation, in addition participants of this clinical trial will also receive Hydroxychloroquine (400 mg per day, oral medication) for 3 months. It is expected that a participant will exhibit a 50% increase of tumor suppressor PAR-4, as well as few, if any, negative side effects from Hydroxychloroquine.

Conditions

Prostate Cancer Recurrent

Keywords

Prostate Cancer; Oligometastatic Prostate Cancer; Limited Metastatic Disease; Metastatic Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Participants With Greater Than or Equal to 50% Induction in Serum PAR4 Levels

  Number of participants that attained greater than or equal to 50% induction over baseline of PAR-4 levels as measured via serum or plasma blood sample

  90 days

Secondary Outcomes (3)

• Change in Serum Prostate Specific Antigen (PSA) Levels

  5 timepoints: baseline, 30-, & 90-days post-HCQ initiation; and at 6- and 12-mos follow-up

• Number of Participants With Progression-Free Survival

  1 year progression free survival

• Number of Participants With Androgen Deprivation Therapy (ADT)-Free Survival

  1 year ADT free survival

Study Arms (1)

Hydroxychloroquine

EXPERIMENTAL

Hydroxychloroquine (HCQ) DOSAGE FORM: 200 mg tablet, oral route DOSAGE: 200 mg BID by mouth, for a total daily dose of 400 mg FREQUENCY: HCQ is taken twice daily (morning and night) with food. DURACTION OF HCQ: 90-days

Drug: Hydroxychloroquine Sulfate 200Mg Tab

Interventions

Hydroxychloroquine Sulfate 200Mg Tab DRUG

Twice daily for 90-days, administered two weeks prior to radiation/surgery of oligometastatic lesions

Also known as: Hydroxychloroquine, plaquenil, plaquenil sulfate, quineprox

Hydroxychloroquine

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed prostate cancer that has recurred
• Three or fewer synchronous metastatic lesions (on imaging) with no evidence of residual local disease
• ECOG performance status 0 - 2
• Approval by screening eye exam (disqualifying baseline conditions listed below)
• Ability to provide informed consent

You may not qualify if:

• Receipt of hydroxychloroquine (HCQ) within the past 6 months
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to HCQ
• Use of contraindicated medications,
• Macular degeneration
• Cataracts
• Severe baseline visual impairment, retinopathy or visual field changes
• Presence of only one functional eye
• Prior treatment with ADT including:
• Previous history of radiation or surgery to a metastatic site
• Serum testosterone less than 50 ng/ml
• History of orchiectomy
• History of pathologic fracture or spinal cord compression
• Brain or CNS metastases
• History of G-6-PD (glucose-6-phosphate dehydrogenase) deficiency
• Uncontrolled intercurrent illness

Sponsors & Collaborators

• Patrick Hensley: lead

Study Sites (1)

Markey Cancer Center - University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Related Publications (8)

• Tosoian JJ, Gorin MA, Ross AE, Pienta KJ, Tran PT, Schaeffer EM. Oligometastatic prostate cancer: definitions, clinical outcomes, and treatment considerations. Nat Rev Urol. 2017 Jan;14(1):15-25. doi: 10.1038/nrurol.2016.175. Epub 2016 Oct 11.

  PMID: 27725639 BACKGROUND

• Taylor LG, Canfield SE, Du XL. Review of major adverse effects of androgen-deprivation therapy in men with prostate cancer. Cancer. 2009 Jun 1;115(11):2388-99. doi: 10.1002/cncr.24283.

  PMID: 19399748 BACKGROUND

• Burikhanov R, Shrestha-Bhattarai T, Hebbar N, Qiu S, Zhao Y, Zambetti GP, Rangnekar VM. Paracrine apoptotic effect of p53 mediated by tumor suppressor Par-4. Cell Rep. 2014 Jan 30;6(2):271-7. doi: 10.1016/j.celrep.2013.12.020. Epub 2014 Jan 9.

  PMID: 24412360 BACKGROUND

• Hebbar N, Wang C, Rangnekar VM. Mechanisms of apoptosis by the tumor suppressor Par-4. J Cell Physiol. 2012 Dec;227(12):3715-21. doi: 10.1002/jcp.24098.

  PMID: 22552839 BACKGROUND

• Kimura T, Takabatake Y, Takahashi A, Isaka Y. Chloroquine in cancer therapy: a double-edged sword of autophagy. Cancer Res. 2013 Jan 1;73(1):3-7. doi: 10.1158/0008-5472.CAN-12-2464.

  PMID: 23288916 BACKGROUND

• Ratikan JA, Sayre JW, Schaue D. Chloroquine engages the immune system to eradicate irradiated breast tumors in mice. Int J Radiat Oncol Biol Phys. 2013 Nov 15;87(4):761-8. doi: 10.1016/j.ijrobp.2013.07.024.

  PMID: 24138918 BACKGROUND

• Burikhanov R, Hebbar N, Noothi SK, Shukla N, Sledziona J, Araujo N, Kudrimoti M, Wang QJ, Watt DS, Welch DR, Maranchie J, Harada A, Rangnekar VM. Chloroquine-Inducible Par-4 Secretion Is Essential for Tumor Cell Apoptosis and Inhibition of Metastasis. Cell Rep. 2017 Jan 10;18(2):508-519. doi: 10.1016/j.celrep.2016.12.051.

  PMID: 28076793 BACKGROUND

• Wang P, Burikhanov R, Jayswal R, Weiss HL, Arnold SM, Villano JL, Rangnekar VM. Neoadjuvant administration of hydroxychloroquine in a phase 1 clinical trial induced plasma Par-4 levels and apoptosis in diverse tumors. Genes Cancer. 2018 May;9(5-6):190-197. doi: 10.18632/genesandcancer.181.

  PMID: 30603055 BACKGROUND

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Hydroxychloroquine

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Patrick Hensley
• Organization: University of Kentucky College of Medicine

patrick.hensley@uky.edu

859-562-3223

Study Officials

• Patrick J Hensley, MD

  University of Kentucky

  PRINCIPAL INVESTIGATOR

• Peng Wang, MD

  University of Kentucky

  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: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor, Dept of Urology

Model Details: Single arm, non-blinded, open label clinical trial

Study Record Dates

• First Submitted: July 1, 2019
• First Posted: July 8, 2019
• Study Start: December 3, 2019
• Primary Completion: March 8, 2024
• Study Completion: March 8, 2024
• Last Updated: April 11, 2025
• Results First Posted: April 11, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: 6 months after publication

Locations

US (1)