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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Rutgers, The State University of New Jersey ( University of Medicine and Dentistry New Jersey )
ClinicalTrials.gov Identifier:
NCT00726596
First received: July 31, 2008
Last updated: June 3, 2013
Last verified: May 2013
  Purpose

This phase II trial is studying how well hydroxychloroquine works in treating patients with rising prostate-specific antigen (PSA) levels after local therapy for prostate cancer.


Condition Intervention Phase
Prostate Cancer
Drug: hydroxychloroquine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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.

Resource links provided by NLM:


Further study details as provided by Rutgers, The State University of New Jersey:

Primary Outcome Measures:
  • Prostate-specific antigen (PSA) response [ Time Frame: 6 years ] [ Designated as safety issue: No ]
    PSA response will be defined as a change in slope of at least 25%, when log (PSA) is plotted vs. time


Secondary Outcome Measures:
  • Effect on peripheral blood mononuclear cell (PBMC) LC3 expression by the use of hydroxychloroquine [ Time Frame: 6 years ] [ Designated as safety issue: No ]
    A change of at least 25% from baseline will be considered to be a significant response

  • Effect on PBMC autophagic vesicle formation by the use of hydroxychloroquine [ Time Frame: 6 years ] [ Designated as safety issue: No ]
  • Expression of Beclin-1 in a population of patients having undergone local treatment with prostatectomy [ Time Frame: 6 years ] [ Designated as safety issue: No ]
  • Feasibility and safety of administering hydroxychloroquine in this population of patients. Rate of adverse events [ Time Frame: 6 years ] [ Designated as safety issue: Yes ]

Enrollment: 64
Study Start Date: August 2008
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00726596

Locations
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
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
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
University of Medicine and Dentistry New Jersey
Investigators
Principal Investigator: Mark Stein, MD Rutgers Cancer Institute of New Jersey
  More Information

Additional Information:
No publications provided

Responsible Party: Rutgers, The State University of New Jersey ( University of Medicine and Dentistry New Jersey )
ClinicalTrials.gov Identifier: NCT00726596     History of Changes
Other Study ID Numbers: 080803, P30CA072720, 0220080115
Study First Received: July 31, 2008
Last Updated: June 3, 2013
Health Authority: United States: Institutional Review Board

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
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Hydroxychloroquine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on April 22, 2014