Clinical trial NCT00726596: Hydroxychloroquine in Treating Patients With Rising PSA Levels After Local Therapy for Prostate Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: recurrent prostate cancer
stage IV prostate cancer
Prostate-Specific Antigen
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
Collaborators: name: Rutgers Cancer Institute of New Jersey
name: National Cancer Institute (NCI)
First posted: 2008-08-01
Enrollment: 64
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Prostate-specific Antigen (PSA) Response
timeFrame: 6 years
Secondary outcomes:
measure: Effect on Peripheral Blood Mononuclear Cell (PBMC) LC3 Expression by the Use of Hydroxychloroquine
timeFrame: 6 years
measure: Effect on PBMC Autophagic Vesicle Formation by the Use of Hydroxychloroquine
timeFrame: 6 years
measure: Expression of Beclin-1 in a Population of Patients Having Undergone Local Treatment With Prostatectomy
timeFrame: 6 years
measure: Feasibility and Safety of Administering Hydroxychloroquine in This Population of Patients. Rate of Adverse Events
timeFrame: 6 years
Other outcomes:
Locations:
city: Hamilton
country: United States
facility: Cancer Institute of New Jersey at Hamilton
state: New Jersey
city: Morristown
country: United States
facility: Carol G. Simon Cancer Center at Morristown Memorial Hospital
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Summit
country: United States
facility: Overlook Hospital
state: New Jersey
city: Voorhees
country: United States
facility: Cooper University Hospital Cancer Institute
state: New Jersey
Study officials:
affiliation: Rutgers Cancer Institute of New Jersey
name: Biren Saraiya, MD
role: PRINCIPAL_INVESTIGATOR
References: