Skip to main content

Hydroxychloroquine for the Treatment of Recurrent, Oligometastatic Prostate Cancer

Trial Status: Active

This phase II trial studies how well hydroxychloroquine works in treating patients with prostate cancer that has come back (recurrent) and has spread to a limited number of sites (oligometastatic). PAR-4 is a protein that causes cell death in cancer cells, but the amount of it made by normal cells is not enough to cause massive cancer cell death. Hydroxychloroquine may increase PAR-4 levels which helps kill more cancer cells.

Inclusion Criteria

  • Males age 18 and over
  • Histologically confirmed prostate cancer that has recurred following primary definitive treatment of localized prostate cancer (either surgery, radiotherapy or both) * Prostate-specific antigen (PSA) biochemical recurrence defined as either: ** PSA >= 0.2 ng/dl following radical prostatectomy ** PSA increase >= 2 ng/mL above PSA nadir value following radiotherapy of primary tumor
  • Five or fewer synchronous metastatic lesions (on imaging) with no evidence of residual local disease
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2
  • Approval by screening eye exam (disqualifying baseline conditions listed below)
  • Ability to provide informed consent

Exclusion Criteria

  • Hydroxychloroquine-specific rule-outs: * Receipt of HCQ within the past 6 months * History of allergic reactions attributed to compounds of similar chemical or biologic composition to hydroxychloroquine * Use of contraindicated medications, including but not limited to combination antiretroviral therapy and enzyme-inducing anti-epileptics
  • Macular degeneration or concurrent macular disease. Eligibility in the presence of other eye/visual impairments (cataracts, severe retinopathy, severe visual impairment at baseline, presence of only one functional eye) will be at the discretion of the treating physician based on eye exam by ophthalmologist
  • Prior treatment with ADT including: * ADT for treatment of metastatic disease * ADT as adjuvant therapy prior to surgery/radiation within 1 year of enrollment
  • Previous history of radiation or surgery to a metastatic site
  • Previous treatment with any of the following: * Abiraterone * Enzalutamide * Apalutamide * Antiretroviral therapy * Chemotherapy * Immunotherapy * Radioisotopes
  • Serum testosterone less than 50 ng/ml
  • History of orchiectomy
  • History of pathologic fracture or spinal cord compression
  • Brain or central nervous system (CNS) metastases
  • History of G-6-PD (glucose-6-phosphate dehydrogenase) deficiency
  • Uncontrolled intercurrent illness including but not limited to the following: * Ongoing or active infection * Symptomatic congestive heart failure * Unstable angina pectoris * Cardiac arrhythmia
  • Psychiatric illness and/or social situations that would limit compliance with study requirements
  • Patients taking other investigational agents


University of Kentucky / Markey Cancer Center
Status: ACTIVE
Contact: Andrew Callaway James
Phone: 859-323-7093


I. Assess the rate of attainment of a 50% increase in tumor suppressor PAR-4 levels from baseline in patients treated with 90-days of hydroxychloroquine (HCQ) in combination with radiation or surgery for recurrent, oligometastatic prostate cancer.


I. Median progression-free survival (time to clinical progression).

II. 1- and 3-year androgen deprivation therapy (ADT) free survival.

III. HCQ treatment toxicity (adverse events [AEs] and serious adverse events [SAEs] during HCQ administration) and radiation toxicity to be assessed and recorded utilizing the Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.

IV. Immunological effect of HCQ by analyzing peripheral blood mononuclear cells (PBMCs) at day 0 and day 30 of treatment, and also, day 60 (+ 6 weeks) of treatment.

V. Quality of life as measured by the European Organization of Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) - Core (C) 30 + QLQ - Prostate (PR) 25.


Patients receive hydroxychloroquine orally (PO) twice daily (BID) for 2 weeks, then undergo standard of care stereotactic body radiation therapy (SBRT) or metastasectomy. Patients then receive hydroxychloroquine PO BID beginning post-operative day 1 for 3 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30, 60, and 90 days, at 6 months, then at 1, 2, and 3 years.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
University of Kentucky / Markey Cancer Center

Principal Investigator
Andrew Callaway James

  • Primary ID MCC-19-GU-72
  • Secondary IDs NCI-2019-08359
  • ID NCT04011410