OBJECTIVES:

• Determine the safety and toxicity of sequential vaccination with vaccinia-PSA-TRICOM vaccine and fowlpox-PSA-TRICOM vaccine in patients with metastatic prostate cancer. (Phase I closed to accrual as of 6/2/04.)
• Determine the impact of sargramostim (GM-CSF) and fowlpox-GM-CSF on immunologic response in patients treated with these vaccines.
• Determine the change in prostate-specific antigen-specific T cells in patients treated with these vaccines.
• Determine objective antitumor response in patients treated with these vaccines.

OUTLINE: This is a pilot phase I dose-escalation study (phase I closed to accrual as of 6/2/04) followed by a randomized phase II study.

• Cohorts of 3-6 patients are sequentially assigned to 1 of 5 treatment regimens to determine the optimal regimen. The optimal regimen is defined as the regimen preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
• Regimen A: Patients receive fowlpox-PSA-TRICOM vaccine (F-PSA-TRI) subcutaneously (SC) on days 1, 29, and 57.
• Regimen B: Patients receive vaccinia-PSA-TRICOM vaccine (VPSA-TRI) SC on day 1 and F-PSA-TRI SC on days 29 and 57.
• Regimen C: Patients receive VPSA-TRI and F-PSA-TRI as in regimen B and sargramostim (GM-CSF) SC on days 1-4, 29-32, and 57-60.
• Regimen D: Patients receive VPSA-TRI and F-PSA-TRI as in regimen B and fowlpox-sargramostim (rf-GM-CSF) SC on days 1, 29, and 57.
• Regimen E: Patients receive VPSA-TRI and F-PSA-TRI as in regimen B and a higher dose of rf-GM-CSF as in regimen D.
• Patients are randomized to 1 of 4 treatment arms, based on the assumption that all 5 regimen levels in phase I are completed.
• Arm I: Patients receive VPSA-TRI and F-PSA-TRI as in regimen B.
• Arm II: Patients receive VPSA-TRI, F-PSA-TRI, and GM-CSF as in regimen C.
• Arm III: Patients receive VPSA-TRI, F-PSA-TRI, and rf-GM-CSF as in regimen D.
• Arm IV: Patients receive VPSA-TRI, F-PSA-TRI, and rf-GM-CSF as in regimen E. Patients in both phases who do not have disease progression after day 85 may receive monthly F-PSA-TRI vaccinations for 12 weeks, according to their assigned treatment arm. Patients are re-evaluated on day 170 and receive an additional F-PSA-TRI vaccination with subsequent F-PSA-TRI vaccinations every 12 weeks thereafter in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed annually for 15 years.

PROJECTED ACCRUAL: A maximum of 62 patients (up to 30 for phase I [closed to accrual as of 6/2/04] and a total of 32 [8 per treatment arm] for phase II) will be accrued for this study within 2 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed prostate cancer, meeting the following criteria:
• Metastatic disease
• Androgen insensitive
• Progression after prior standard hormonal therapy for metastatic prostate cancer
• Prior antiandrogen therapy requires a rising prostate-specific antigen (PSA) after withdrawal of at least 4 weeks
• Prior bicalutamide therapy requires a rising PSA after withdrawal of at least 6 weeks
• Objective evidence of metastasis or relapsing local disease as evidenced by a rising PSA and at least 1 of the following:
• Positive bone scan
• Palpable disease
• The following positive imaging studies:
• Two consecutively rising PSA levels taken at least 1 week apart, with 1 level that is 50% above the nadir reached after the last therapeutic maneuver (as long as the last measurement is at least 5 ng/mL)
• At least 1 lesion consistent with metastatic cancer on technetium Tc 99m whole body scintigraphy AND/OR
• Soft-tissue metastases as measured by appropriate modalities (i.e., imaging and palpation)
• HLA-A2 positive (phase II only)
• No brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• More than 6 months

Hematopoietic

• Granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Lymphocyte count at least 500/mm^3
• Hemoglobin at least 10 g/dL

Hepatic

• Bilirubin less than 1.5 mg/dL
• AST and ALT less than 2.5 times upper limit of normal
• Hepatitis B negative
• Hepatitis C negative

Renal

• Creatinine clearance greater than 60 mL/min
• Creatinine normal
• No proteinuria 1,000 mg or greater by 24-hour urine collection
• No hematuria*
• No abnormal sediment* NOTE: *Patient may be eligible provided the underlying cause is determined to be non-renal

Cardiovascular

• No prior unstable or newly diagnosed angina pectoris
• No myocardial infarction within the past 6 months
• No New York Heart Association class II-IV congestive heart failure
• No clinically significant cardiomyopathy requiring treatment

Immunologic

• HIV negative
• No active infection within the past 3 days
• No allergy or untoward reaction to prior vaccinia virus vaccination
• No concurrent significant autoimmune disease that is active or potentially life-threatening if activated
• No known allergy to eggs

Other

• Fertile patients must use effective contraception
• No other active malignancy within the past 2 years except nonmelanoma skin cancer or carcinoma in situ of the bladder
• No other concurrent serious or life-threatening illness
• No eczema or eczematoid skin disorders
• No acute, chronic, or exfoliative skin conditions, including:
• Atopic dermatitis
• Burns
• Impetigo
• Varicella zoster
• Severe acne
• Other open rashes or wounds
• No close household contact with persons meeting any of the following criteria for at least 3 weeks after vaccination:
• Prior or active eczema or other eczematoid skin disorders
• Acute, chronic, or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds)
• Pregnant or nursing women
• Children under 5 years of age
• Immunodeficient or immunosuppressed (including HIV infection) individuals
• Willing and able to travel to the National Institutes of Health for follow-up

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior PSA vaccine therapy (phase II only)

Chemotherapy

• More than 3 years since prior therapy with any of the following (phase II only):
• Docetaxel
• Paclitaxel
• Doxorubicin
• Cisplatin
• Carboplatin
• Mitoxantrone
• Estramustine
• Cyclophosphamide
• Irinotecan
• Topotecan

Endocrine therapy

• See Disease Characteristics
• No concurrent steroid therapy (except topical or inhaled steroids)
• Patients concurrently receiving luteinizing hormone-releasing factor analog therapy must continue therapy during study participation

Radiotherapy

• At least 4 weeks since prior radiotherapy

Surgery

• No prior splenectomy

Other

• Recovered from all prior therapy
• No concurrent antibiotics
• No other concurrent antitumor therapy