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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00726596
Recruitment Status : Unknown
Verified December 2015 by Rutgers, The State University of New Jersey.
Recruitment status was:  Active, not recruiting
First Posted : August 1, 2008
Last Update Posted : December 17, 2015
Rutgers Cancer Institute of New Jersey
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Rutgers, The State University of New Jersey

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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: hydroxychloroquine Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 64 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: NJ 1808: Autophagic Cell Death With Hydroxychloroquine in Patients With Hormone-Dependent Prostate-Specific Antigen Progression After Local Therapy For Prostate Cancer.
Study Start Date : August 2008
Actual Primary Completion Date : February 2014
Estimated Study Completion Date : October 2016

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Hydroxychloroquine
Hydroxychloroquine - 400 mg (cohort A) Hydroxychloroquine - 600 mg (cohort B)
Drug: hydroxychloroquine
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).

Primary Outcome Measures :
  1. Prostate-specific antigen (PSA) response [ Time Frame: 6 years ]
    PSA response will be defined as a change in slope of at least 25%, when log (PSA) is plotted vs. time

Secondary Outcome Measures :
  1. Effect on peripheral blood mononuclear cell (PBMC) LC3 expression by the use of hydroxychloroquine [ Time Frame: 6 years ]
    A change of at least 25% from baseline will be considered to be a significant response

  2. Effect on PBMC autophagic vesicle formation by the use of hydroxychloroquine [ Time Frame: 6 years ]
  3. Expression of Beclin-1 in a population of patients having undergone local treatment with prostatectomy [ Time Frame: 6 years ]
  4. Feasibility and safety of administering hydroxychloroquine in this population of patients. Rate of adverse events [ Time Frame: 6 years ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria

  • 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:

    1. 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
    2. 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)
    3. 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.
  • Must sign informed consent.

Exclusion Criteria

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00726596

United States, New Jersey
Cancer Institute of New Jersey at Hamilton
Hamilton, New Jersey, United States, 08690
Carol G. Simon Cancer Center at Morristown Memorial Hospital
Morristown, New Jersey, United States, 07962
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08903
Overlook Hospital
Summit, New Jersey, United States, 07901
Cooper University Hospital Cancer Institute
Voorhees, New Jersey, United States, 08043
Sponsors and Collaborators
Rutgers, The State University of New Jersey
Rutgers Cancer Institute of New Jersey
National Cancer Institute (NCI)
Principal Investigator: Mark Stein, MD Rutgers Cancer Institute of New Jersey

Responsible Party: Rutgers, The State University of New Jersey Identifier: NCT00726596     History of Changes
Other Study ID Numbers: 080803
P30CA072720 ( U.S. NIH Grant/Contract )
0220080115 ( Other Identifier: IRB )
NCI-2012-00528 ( Other Identifier: NCI # )
First Posted: August 1, 2008    Key Record Dates
Last Update Posted: December 17, 2015
Last Verified: December 2015

Keywords provided by Rutgers, The State University of New Jersey:
recurrent prostate cancer
stage IV prostate cancer
Prostate-Specific Antigen

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents