RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Vaccine therapy may make the body build an immune response to kill tumor cells. Interleukin-2 may stimulate the white blood cells to kill tumor cells.

PURPOSE: This randomized phase II trial is studying radiation therapy, vaccine therapy, and interleukin-2 to see how well they work compared to radiation therapy alone in treating patients with prostate cancer.

OBJECTIVES:

• Compare immunologic response, as measured by the increase in prostate-specific antigen (PSA)-specific T-cell precursors, in patients with localized prostate cancer treated with vaccine comprising recombinant vaccinia-PSA and rV-B7.1 plus recombinant fowlpox-PSA vaccine, sargramostim (GM-CSF), and low-dose interleukin-2 (IL-2) vs no vaccine regimen.
• Determine the safety and tolerability of this regimen in combination with radiotherapy in these patients.
• Compare the toxic effects of IL-2 in patients treated with these regimens.

OUTLINE: This is a randomized study. Patients are stratified according to planned radiotherapy (irradiation alone vs irradiation and radioactive implant) and planned hormonal therapy (yes vs no). Patients are randomized to treatment arms I or II and, once accrual on these arms is complete, up to 20 patients (9-10 HLA-A2 positive) are accrued to arm III.

• Arm I: Patients receive vaccine comprising recombinant vaccinia-PSA admixed with rV-B7.1 subcutaneously (SC) on day 2. On days 30, 58, 86, 114, 142, 170, and 198, patients receive recombinant fowlpox-PSA vaccine SC. Beginning on day 86, patients undergo radiotherapy 5 days a week with total duration dependent upon whether patient undergoes radiotherapy alone or radiotherapy plus brachytherapy. Patients receive sargramostim (GM-CSF) SC on days 1-4, 29-32, 57-60, 85-88, 113-116, 141-144, 169-172, and 197-200. Patients receive low-dose interleukin-2 SC on days 8-12, 36-40, 64-68, 91-95, 120-124, 148-152, 176-180, and 204-208.
• Arm II: Patients undergo radiotherapy 5 days a week with total duration dependent upon whether patient undergoes radiotherapy alone or radiotherapy plus brachytherapy.
• Arm III: Patients undergo radiotherapy and receive recombinant vaccinia-PSA admixed with rV-B7.1 vaccine and GM-CSF as in arm I. Patients also receive a lower dose of IL-2 SC on days 8-21, 36-49, 64-77, 91-104, 120-133, 148-161, 176-189, and 204-217.

Patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually for 13 years.

PROJECTED ACCRUAL: A total of 48-49 patients (19 for arm I, 11 for arm II, and 18-19 for arm III) will be accrued for this study within 10-15 months.

• Biological: aldesleukin
• Biological: recombinant fowlpox-prostate apecific antigen vaccine
• Biological: recombinant vaccinia prostate-specific antigen vaccine
• Biological: recombinant vaccinia-B7.1 vaccine
• Biological: sargramostim
• Radiation: brachytherapy
• Radiation: radiation therapy

• Lechleider RJ, Arlen PM, Tsang KY, Steinberg SM, Yokokawa J, Cereda V, Camphausen K, Schlom J, Dahut WL, Gulley JL. Safety and immunologic response of a viral vaccine to prostate-specific antigen in combination with radiation therapy when metronomic-dose interleukin 2 is used as an adjuvant. Clin Cancer Res. 2008 Aug 15;14(16):5284-91.
• Gulley JL, Arlen PM, Bastian A, Morin S, Marte J, Beetham P, Tsang KY, Yokokawa J, Hodge JW, Menard C, Camphausen K, Coleman CN, Sullivan F, Steinberg SM, Schlom J, Dahut W. Combining a recombinant cancer vaccine with standard definitive radiotherapy in patients with localized prostate cancer. Clin Cancer Res. 2005 May 1;11(9):3353-62. Erratum in: Clin Cancer Res. 2006 Jan 1;12(1):322.

DISEASE CHARACTERISTICS:

• Histologically confirmed localized adenocarcinoma of the prostate that has not undergone local therapy
• Must be a candidate for definitive radiotherapy and agree to be treated with external beam radiotherapy alone or in combination with brachytherapy
• HLA-A2 positive (arms I and II and at least 9 patients accrued to arm III)
• Prior vaccinia immunization required

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Zubrod 0-1 OR
• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Absolute lymphocyte count at least 600/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 8.0 g/dL

Hepatic:

• Bilirubin no greater than 1.6 mg/dL
• AST and ALT no greater than 4 times normal
• No hepatic dysfunction that may be exacerbated by interleukin-2 (IL-2)

Renal:

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance greater than 60 mL/min
• No abnormal urinalysis (proteinuria less than 150 g/24 hours) unless cause is non-renal
• No concurrent renal disease that may be exacerbated by IL-2

Cardiovascular:

• No concurrent cardiac disease that may be exacerbated by IL-2

Pulmonary:

• No concurrent pulmonary disease that may be exacerbated by IL-2

Immunologic:

• HIV negative
• No history of allergy or adverse reaction to prior vaccinia vaccine
• No known allergy to eggs
• No active infection requiring antibiotics (including chronic suppressive therapy)
• No active or prior eczema or other eczematoid skin disorders
• No acute, chronic, or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds)
• No altered immune function

• No autoimmune disease, including any of the following:

  • Autoimmune neutropenia, thrombocytopenia, or hemolytic anemia
  • Systemic lupus erythematosus
  • Sjögren's syndrome
  • Scleroderma
  • Myasthenia gravis
  • Goodpasture's syndrome
  • Addison's disease
  • Hashimoto's thyroiditis
  • Active Graves' disease

Other:

• No other serious illness
• No other malignancy within the past 3 years except basal cell or squamous cell skin cancer
• No prior seizures, encephalitis, or multiple sclerosis

• No close household contact with the following individuals for at least two weeks after vaccinia inoculation:

  • Individuals with active or prior 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 condition resolves
  • Children under age 5
  • Pregnant or nursing women
  • Immunodeficient or immune-suppressed individuals by disease or therapy, including HIV infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics

Chemotherapy:

• Not specified

Endocrine therapy:

• Concurrent hormonal therapy allowed
• No concurrent glucocorticoids
• No concurrent dexamethasone or other corticosteroids as antiemetics

Radiotherapy:

• See Disease Characteristics
• No prior radiotherapy to more than 50% of nodal groups

Surgery:

• No prior disease-related surgery
• No prior splenectomy

Other:

• At least 3 days since prior antibiotics