Hydroxychloroquine in Treating Patients With Rising PSA Levels After Local Therapy for Prostate Cancer

NCT00726596 | Completed Phase 2 Results

• 4 other identifiers: 0220080115P30CA072720NCI-2012-00528080803
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 5

Brief Summary

This phase II trial studies how well hydroxychloroquine works in treating patients with previously treated prostate cancer. Autophagy destroys proteins and other substances in cells and may be used by prostate cancer cells to survive. Hydroxychloroquine, which blocks autophagy, may slow the growth of and possibly kill prostate cancer cells.

Conditions

Prostate Cancer

Keywords

recurrent prostate cancer; stage IV prostate cancer; Prostate-Specific Antigen

Outcome Measures

Primary Outcomes (1)

• Prostate-specific Antigen (PSA) Response

  PSA response will be defined as a change in slope of at least 25%, when log (PSA) is plotted vs. time

  6 years

Secondary Outcomes (4)

• Effect on Peripheral Blood Mononuclear Cell (PBMC) LC3 Expression by the Use of Hydroxychloroquine

  6 years

• Effect on PBMC Autophagic Vesicle Formation by the Use of Hydroxychloroquine

  6 years

• Expression of Beclin-1 in a Population of Patients Having Undergone Local Treatment With Prostatectomy

  6 years

• Feasibility and Safety of Administering Hydroxychloroquine in This Population of Patients. Rate of Adverse Events

  6 years

Study Arms (1)

Hydroxychloroquine

EXPERIMENTAL

Hydroxychloroquine - 400 mg (cohort A) Hydroxychloroquine - 600 mg (cohort B)

Drug: hydroxychloroquine

Interventions

hydroxychloroquine DRUG

Hydroxychloroquine will be taken at a dose of 200 mg twice per day in the first 27 patients (cohort A). Once cohort A completed, the dose of hydroxychloroquine will then be increased to 600mg per day (200mg three times per day)(cohort B).

Hydroxychloroquine

Eligibility Criteria

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

You may qualify if:

• Histologically proven stage D0 prostate cancer (i.e., tumor originally diagnosed as being limited to the prostate) or D1 prostate cancer (metastatic to regional lymph nodes) and have a rising PSA value after definitive local therapy.
• Must have undergone local treatment via prostatectomy or radiation therapy.
• Must have PSA progression after local treatment:
• PSA values for patients after surgery must be \> 0.2 ng/mL, determined by two measurements, at least 1 month apart and at least 6 months after prostatectomy
• PSA values for patients after radiation must be ≥ 2.0 ng/ml greater than the nadir achieved after radiation, determined by two measurements at 1 month apart and at least 6 months after the radiation treatment is completed. (Patients who received adjuvant or salvage radiation after prostatectomy must have PSA of \>0.2)
• The first two PSA values (in 5.1.3a and 5.1.3b), along with a third (study baseline) value must all be rising (i.e., there must be an overall rising trajectory, such that the third value cannot be lower than the first value).
• Baseline bone scan and CT abdomen/pelvis demonstrating no metastatic disease.
• Age ≥ 18 years
• Estimated life expectancy of at least 6 months.
• ECOG performance status \< 2. (see Appendix B)
• A WBC \> 3500/μl, ANC \>1500/μl, hemoglobin \> 10 g/dl, and platelet count \>100,000/μl are required.
• Adequate renal function (serum creatinine \< 1.5 mg/dL or creatinine clearance \> 50 ml/min).
• Total bilirubin must be within 1.5X the normal institutional limits. If total bilirubin is outside the normal institutional limits, assess direct bilirubin. The direct bilirubin must be within normal parameters. Transaminases (SGOT and/or SGPT) must be less than 2.5X the institutional upper limit of normal.
• Documented ophthalmic exam within the last twelve months demonstrating no evidence of retinopathy. Patients with retinal changes will be considered for enrollment with written clearance from a board certified ophthalmologist.
• Must have a serum total testosterone level ≥150 ng/dL at the time of enrollment within 4 weeks prior to randomization.

You may not qualify if:

• Serious concomitant systemic disorder that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator.
• Must be off ADT in the neoadjuvant, adjuvant and/or salvage setting for at least 3 months and have a testosterone level \> 150 ng/dl.
• Second primary malignancy except most situ carcinoma (e.g. adequately treated non-melanomatous carcinoma of the skin) or other malignancy treated at least 5 years previously with no evidence of recurrence.
• Rheumatoid arthritis or systemic lupus erythematosus treatment.
• Psoriasis.
• Receiving any disease-modifying anti-rheumatic drug (DMARD).
• Active clinically significant infection requiring antibiotics.
• G6PD deficiency.
• Taking other commercially available medications which may theoretically either stimulate or inhibit autophagy, which are calcitriol and chloroquine.
• Taking medications which may lead to interactions with hydroxychloroquine, including penicillamine, telbivudine, botulinum toxin, digoxin, and propafenone.
• Must not have visual field changes from prior 4-aminoquinoline compound use.
• Must not be taking hydroxychloroquine for treatment or prophylaxis of malaria.
• History of hypersensitivity to 4-aminoquinoline compound.

Sponsors & Collaborators

• Rutgers, The State University of New Jersey: lead
• Rutgers Cancer Institute of New Jersey: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (5)

Cancer Institute of New Jersey at Hamilton

Hamilton, New Jersey, 08690, United States

Location

Carol G. Simon Cancer Center at Morristown Memorial Hospital

Morristown, New Jersey, 07962, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Overlook Hospital

Summit, New Jersey, 07901, United States

Location

Cooper University Hospital Cancer Institute

Voorhees Township, New Jersey, 08043, United States

Location

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

Limitations and Caveats

Research correlatives were not analyzed because the study was unfunded.

Results Point of Contact

• Title: Mark Stein, MD
• Organization: Rutgers Cancer Institute of New Jersey

steinmn@cinj.rutgers.edu

732-235-5773

Study Officials

• Biren Saraiya, MD

  Rutgers Cancer Institute of New Jersey

  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: Assistant Professor of Medicine Medical Oncology

Study Record Dates

• First Submitted: July 31, 2008
• First Posted: August 1, 2008
• Study Start: August 1, 2008
• Primary Completion: February 1, 2014
• Study Completion: January 1, 2018
• Last Updated: June 16, 2022
• Results First Posted: June 16, 2022

Record last verified: 2022-06

Locations

US (5)