This phase II trial is studying how well 17-AAG works in treating patients with metastatic prostate cancer that did not respond to previous hormone therapy. Drugs used in chemotherapy, such as 17-AAG, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PRIMARY OBJECTIVES:

I. Determine the prostate-specific antigen (PSA) response in patients with hormone-refractory metastatic prostate cancer treated with 17-N-allylamino-17-demethoxygeldanamycin (17-AAG).

SECONDARY OBJECTIVES:

I. Determine the overall survival and disease-free survival rate in patients treated with this drug.

II. Determine the safety profile of this drug in these patients. III. Determine the duration of PSA response and PSA control in patients treated with this drug.

IV. Determine the partial and complete response rates in patients with measurable disease treated with this drug.

V. Correlate changes in expression levels of interleukin-6, maspin, and NF-kappaB in serum and tissue with cancer and treatment-related outcomes in patients treated with this drug.

OUTLINE: This is a multicenter study. Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over 2-6 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response (CR) receive 2 additional courses of treatment beyond documentation of CR.

After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 16-28 patients will be accrued for this study within 20 months.

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the prostate

  • Metastatic disease

• Measurable or evaluable disease

  • Prostate-specific antigen (PSA) ≥ 5 ng/mL OR new areas of bony metastases on bone scan are required for patients with no measurable disease

• Objective disease progression OR rising PSA despite receiving androgen deprivation therapy and undergoing antiandrogen withdrawal

  • Patients with a rising PSA must have 2 successive elevations (measured ≥ 1 week apart)

• Must be castrate (testosterone < 50 ng/mL)

  • Luteinizing hormone-releasing hormone agonist therapy must be continued during study participation to maintain castrate levels of testosterone

• Must have received ≥ 1 prior chemotherapy regimen for metastatic disease

• No known brain metastases requiring active therapy

  • Previously treated asymptomatic brain metastases allowed

• Performance status - ECOG 0-2

• At least 12 weeks

• Absolute neutrophil count ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• Hemoglobin ≥ 8.0 g/dL

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)

• SGOT and/or SGPT ≤ 2.5 times ULN AND alkaline phosphatase normal

• Alkaline phosphatase ≤ 4 times ULN AND SGOT and/or SGPT normal

• Creatinine clearance ≥ 60 mL/min

• Creatinine normal

• QTc < 450 msec for male patients

• LVEF > 40% by MUGA

• EF normal by MUGA if prior anthracycline therapy

• No congenital long QT syndrome

• No left bundle branch block

• Deep venous thrombosis or other clinically significant thromboembolic event within the past 6 months allowed provided patient is clinically stable on anticoagulation therapy

• No history of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)

• No myocardial infarction within the past year

• No cerebrovascular accident or transient ischemic attack within the past 6 months

• No New York Heart Association class III or IV congestive heart failure

• No poorly controlled angina

• No uncontrolled dysrhythmia or dysrhythmias requiring medication

• No active ischemic heart disease within the past 12 months

• No other significant cardiac disease

• Pulmonary embolus allowed within the past 6 months provided patient is clinically stable on anticoagulation therapy

• Fertile patients must use effective contraception

• Willing and able to provide blood samples

• No serious allergy (i.e., hypotension, dyspnea, anaphylaxis, or edema) to eggs

• No other concurrent malignancy or history of a curatively treated malignancy with a survival prognosis of < 5 years

• No known HIV positivity

• No active infection

• No other severe acute or chronic medical or psychiatric condition or laboratory abnormality that would preclude study participation

• At least 4 weeks since prior flutamide (6 weeks for bicalutamide or nilutamide)

• At least 28 days since prior radiotherapy

• No prior radiotherapy field that included the heart (e.g., mantle)

• More than 6 months since prior coronary or peripheral artery bypass grafting

• More than 28 days since prior investigational agents for prostate cancer

• No concurrent agents that interact with cytochrome P450 3A4

• No concurrent warfarin for anticoagulation

  • Concurrent low molecular weight heparin injection allowed

• No concurrent medications that would prolong QTc

• No other concurrent antineoplastic agents

• Concurrent zoledronate for bone metastases or hypercalcemia allowed