• Compare immunologic response by ELISPOT at baseline and at day 113 [ Designated as safety issue: No ]
• Prostate-specific antigen (PSA) changes by monthly serum PSA [ Designated as safety issue: No ]

• Compare immunologic response by ELISPOT at baseline and at day 113
• Prostate-specific antigen (PSA) changes by monthly serum PSA

RATIONALE: Vaccines made from a gene-modified virus may make the body build an effective immune response to kill tumor cells. Giving booster vaccinations may make a stronger immune response and prevent or delay the recurrence of cancer.

PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy in patients with progressive or locally recurrent prostate cancer.

OBJECTIVES:

Primary

• Determine the clinical safety and feasibility of vaccine therapy comprising priming vaccinations of vaccinia-PSA-TRICOM and recombinant fowlpox-GM-CSF (rF-GM-CSF) followed by boosting vaccinations of fowlpox-PSA-TRICOM with or without rF-GM-CSF in patients with progressive or locally recurrent prostate cancer.

Secondary

• Determine changes in prostate-specific antigen-specific T-cell response in HLA-A2-positive patients treated with this regimen.

OUTLINE: This is a dose-escalation study of booster vaccinations comprising vaccinia-PSA-TRICOM (rV-PSA-TRICOM) with or without recombinant fowlpox-GM-CSF (rF-GM-CSF). Patients are assigned to 1 of 5 groups.

• Groups 1 and 2: Patients receive priming vaccinations comprising rV-PSA-TRICOM subcutaneously (SC) and rF-GM-CSF SC on day 1. Patients also receive a booster vaccination comprising fowlpox-PSA-TRICOM (rF-PSA-TRICOM) by intraprostatic (IP) injection on days 29, 57, and 85.
• Groups 3 and 4: Patients receive priming and booster vaccinations as in groups 1 and 2. Patients also receive a booster vaccination comprising rF-GM-CSF IP on days 29, 57, and 85.
• Group 5: Patients receive priming and booster vaccinations as in groups 3 and 4. Patients also receive booster vaccinations comprising rF-PSA-TRICOM SC and rF-GM-CSF SC on days 29, 57, and 85.

Cohorts of 3-6 patients in each group receive escalating doses of booster vaccinations comprising rF-PSA-TRICOM with or without rF-GM-CSF until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Treatment in all groups continues in the absence of unacceptable toxicity or disease progression.

Patients are followed annually for up to 15 years.

PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study within 30 months.

• Biological: fowlpox-PSA-TRICOM vaccine
• Biological: recombinant fowlpox GM-CSF vaccine adjuvant
• Biological: vaccinia-PSA-TRICOM vaccine

DISEASE CHARACTERISTICS:

• Histologically confirmed* adenocarcinoma of the prostate, meeting 1 of the following criteria:

  • Locally recurrent disease after prior local radiotherapy or cryotherapy, defined as 3 consecutive rising prostate-specific antigen levels AND confirmed by biopsy performed ≥ 18 months after completion of radiotherapy
  • Not a candidate for or refused local definitive therapy (surgery or radiation therapy) AND had clinically progressive disease during androgen deprivation therapy, defined as 3 increases in PSA over nadir, separated by ≥ 1 week NOTE: *Patients without a pathological specimen available are eligible provided there is histologic diagnosis of prostate cancer and a clinical course consistent with prostate disease
• Minimal extraprostatic disease allowed
• No clinically active brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 6 months

Hematopoietic

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

Hepatic

• Bilirubin < 1.5 mg/dL (≤ 3.0 mg/dL for patients with Gilbert's syndrome)
• AST and ALT < 2.5 times upper limit of normal
• Hepatitis B and C negative

Renal

• Creatinine < 2.0 mg/dL OR creatinine clearance > 60 mL/min
• No proteinuria, defined as ≥ 1,000 mg of protein on 24-hour urine collection
• No abnormal urine sediment or hematuria unless the underlying cause is determined to be non-renal

Cardiovascular

• No New York Heart Association class II-IV heart disease
• No objective evidence of congestive heart failure by physical exam or imaging

Pulmonary

• No pulmonary disease that causes fatigue or dyspnea during ordinary physical activity

Neurologic

• No history of seizures
• No history of encephalitis
• No history of multiple sclerosis

Gastrointestinal

• No inflammatory bowel disease
• No Crohn's disease
• No ulcerative colitis
• No active diverticulitis

Immunologic

• HIV negative
• History of autoimmunity not requiring systemic immunosuppressive therapy and not threatening vital organ function (e.g., CNS, heart, lungs, kidneys, skin, or gastrointestinal tract) allowed

• No active autoimmune disease, including any of the following:

  • Addison's disease
  • Hashimoto's thyroiditis
  • Systemic lupus erythematosus
  • Sjögren's syndrome
  • Scleroderma
  • Myasthenia gravis
  • Goodpasture's syndrome
  • Graves' disease

• No other altered immune function, including any of the following conditions:

  • History of or active eczema or other eczematoid skin disorders
  • Atopic dermatitis
  • Other skin diseases
  • Open wounds
• No history of allergy or untoward reaction to prior vaccination with vaccinia virus or any component of study treatment
• No serious hypersensitivity to egg products

Other

• Fertile patients must use effective contraception during and for at least 4 months after study treatment

• Able to avoid close household contact with any of the following for at least 3 weeks after each study vaccination:

  • Individuals with a history of or active eczema or other eczematoid skin disorders
  • Individuals with acute, chronic, or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds) until the condition resolves
  • Pregnant or nursing women
  • Children age 3 and under
  • Immunodeficient or immunosuppressed (by disease or therapy) individuals, including HIV-positive individuals
• No other malignancy within the past year except nonmelanoma skin cancer or carcinoma in situ of the bladder
• No other life-threatening illness
• No other serious medical illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior vaccinia unless immune to vaccinia
• No other concurrent immunotherapy

Chemotherapy

• No concurrent anticancer chemotherapy

Endocrine therapy

• See Disease Characteristics
• No steroid eye drops for at least 2 weeks before, during, and for at least 4 weeks after study treatment
• Concurrent hormonal therapy allowed
• No concurrent systemic steroids, including glucocorticoids, except for physiologic doses for systemic steroid replacement or local (i.e., topical, nasal, or inhaled) steroid use

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery

• See Disease Characteristics
• At least 4 weeks since prior surgery
• No prior splenectomy
• No concurrent major surgery

Other

• Recovered from all prior therapy