A Phase II Study of Docetaxel and Modulation of Autophagy With Hydroxychloroquine for Metastatic Hormone Refractory Prostate Cancer

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed prostate cancer

- Metastatic disease, as demonstrated by bone scan and/or CT scan of the
abdomen/pelvis

- Must demonstrate disease progression after initial hormone therapy (including
bicalutamide and flutamide)

- No prior chemotherapy allowed

- No known brain metastases

PATIENT CHARACTERISTICS:

- ECOG performance status 0-1

- Life expectancy ≥ 6 months

- ANC > 1,500/μL

- Hemoglobin > 10 g/dL

- Platelet count > 100,000/mm^3

- Serum creatinine < 2.0 mg/dL or creatinine clearance > 50 mL/min

- Total bilirubin normal

- SGOT and/or SGPT < 1.5 times upper limit of normal (ULN)

- Alkaline phosphatase < 2.5 times ULN

- Fertile patients must use effective contraception during and for 3 months after
completion of study therapy

- No second primary malignancy except for most in situ carcinomas (e.g., adequately
treated nonmelanoma carcinoma of the skin) or other malignancy treated ≥ 5 years ago
with no evidence of recurrence

- No history or symptoms of cardiovascular disease, including any of the following:

- NYHA class II-IV cardiovacular disease within the past 6 months

- Coronary artery disease

- Arrhythmias

- Conduction defects with risk of cardiovascular instability

- Uncontrolled hypertension

- Clinically significant pericardial effusion

- Congestive heart failure

- No uncontrolled intercurrent illness including ongoing active infection that would
limit compliance with study requirements

- No rheumatoid arthritis or systemic lupus erythematosus requiring treatment

- No psoriasis or porphyria

- No known HIV infection

- No hypersensitivity to 4-aminoquinoline compounds, including hydroxychloroquine
sulfate, chloroquine phosphate, and amodiaquine

- No retinal or vision changes from prior 4-aminoquinoline compound use

- No history of severe hypersensitivity reaction to docetaxel or other drugs formulated
with polysorbate 80

- No known G-6PDH deficiency

- Neurotoxicity ≤ grade 1

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Recovered from all prior therapy

- No prior taxane

- At least 4 weeks since prior therapy (including surgery and radiotherapy)

- At least 1 week since prior herbal supplements

- At least 6 weeks since prior bicalutamide

- At least 4 weeks since prior flutamide

- No current hydroxychloroquine for treatment or prophylaxis

- Prior hydroxychloroquine allowed

- No other concurrent investigational or commercial agents or therapies, including
chemotherapy, immunotherapy, hormonal cancer therapy, radiotherapy, surgery for
cancer, or experimental therapy

- Concurrent luteinizing-hormone releasing-hormone agonists allowed