NJ 1808: Autophagic Cell Death With Hydroxychloroquine in Patients With Hormone-Dependent Prostate-Specific Antigen Progression After Local Therapy For Prostate Cancer.

Inclusion 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.