PSA-Based Vaccine and Radiotherapy to Treat Localized Prostate Cancer

This trial will evaluate the immunologic effects of a vaccination regimen in HLA-A2 positive
prostate cancer patients. Eligible patients will have localized prostate cancer and be
willing to undergo definitive local radiotherapy. 30 patients will be randomized in a 2:1
ratio into two cohorts (see schema below) with patients in the vaccine arm receiving
vaccination before, during and after primary standard radiotherapy (external beam alone or
in combination with brachytherapy). When enrollment to these two cohorts is complete,
enrollment will begin with up to 19 (9-10 HLA-A2 positive) patients to a third,
non-randomized vaccine cohort. This cohort C will differ from the first vaccine cohort only
in the IL-2 dose and schedule. The vaccine regimen will be composed of (1) a recombinant
vaccinia virus that expresses the Prostate Specific Antigen gene (rV-PSA), admixed with (2)
a recombinant vaccinia virus that expresses B7.1 costimulatory molecule (rV-B7.1); followed
by (3) sequential vaccinations with recombinant fowlpox virus containing the PSA gene
(rF-PSA). All patients on the vaccine arms will, in addition, receive sargramostim and
aldesleukin as part of their vaccination schedule.

The primary endpoint is to identify immunologic response as measured by in vitro analysis of
the patients peripheral blood cells. The immune response of cohorts A and B will be analyzed
at various times to determine whether a specific immune response can be affected by the
vaccination as well as whether radiotherapy has an effect on that immune response. The serum
PSA will be followed as a secondary endpoint.

All patients with PSA-expressing adenocarcinoma of the prostate will be evaluated for
eligibility that includes a history of prior vaccinia (as vaccine against smallpox) and
immunocompetence.

- INCLUSION CRITERIA:

Patients with histologically confirmed diagnosis of adenocarcinoma of the prostate who are
candidates for definitive radiotherapy, who have not had local therapy but who agree to be
treated with radiotherapy (external beam therapy alone or in combination with
brachytherapy).

Patients must be HLA-A2 positive for cohorts A and B. At least 9 patients must be HLA-A2
positive in cohort C.

Zubrod (ECOG) performance 0-1.

Age greater than or equal to 18 years.

Concurrent hormonal therapy will be allowed.

Patients must have received prior vaccinia (for smallpox immunization). For patients less
than 30 years of age, physician certification of prior smallpox immunization is required.
For patients greater than or equal to age 30, patient recollection and appropriate
vaccination-site scar is sufficient evidence. There must be no history of allergy or
untoward reaction to prior vaccination with vaccinia virus.

Absolute lymphocyte count greater than or equal to 600/mm(3); platelets greater than or
equal to 100,000/mm(3); hemoglobin greater than or equal to 8.0 grams/dl.

The initial urine analysis for eligibility should be less than or equal to grade 1
proteinuria, grade 0 hematuria and no abnormal sediment. Any positive protein, including
trace values, should be evaluated by a 24-hour urine less than or equal to 1 gram per 24
hours. Any other abnormalities in the sediment or the presence of hematuria should be
evaluated by a nephrologist for evidence of underlying renal pathology. Patients may be
eligible if the underlying cause of the abnormality is determined to be non-renal.

Serum bilirubin less than or equal to 1.6 mg/dl, AST and ALT less than or equal to 4 times
normal; serum creatinine less than or equal to 1.5 mg/dl or a creatinine clearance of
greater than 60 ml/min.

Patients must understand and sign informed consent that explains the neoplastic nature of
his disease, the procedures to be followed, the experimental nature of the treatment,
alternative treatments, potential risks and toxicities, and the voluntary nature of
participation.

EXCLUSION CRITERIA:

Patients should have no evidence of being immunocompromised as listed below:

They should have no reactive HIV testing;

They should not have any other diagnosis of altered immune function, autoimmune disease
(autoimmune neutropenia, thrombocytopenia, or hemolytic anemia; systemic lupus
erythematosus, Sjogren syndrome, or scleroderma; myasthenia gravis; Goodpasture syndrome;
Addison's disease, Hashimoto's thyroiditis, or active Graves' disease).

They should not have prior radiation therapy greater than 50% of nodal groups;

They should not have had a prior splenectomy;

They should not be using glucocorticoids (including glucocorticoids for brachytherapy).

The recombinant vaccinia vaccine should not be administered if the following apply to
either recipients or, for at least two weeks after vaccination, their close household
contacts: Persons with active or a history of eczema or other eczematoid skin disorders;
those with other acute, chronic or exfoliative skin conditions (e.g., atopic dermatitis,
burns, impetigo, varicella zoster, severe acne or other open rashes or wound) until
condition resolves; Pregnant or nursing women; Children under 5 years of age; and
immunodeficient or immunosuppressed persons (by disease or therapy) , including HIV
infection. Close household contacts are those who share housing or have close physical
contact.

Other serious intercurrent illness. Patients with active infections requiring antibiotic
treatment (including chronic suppressive therapy) are not eligible until the infection has
cleared and the antibiotics have been stopped for at least three days.

History of other malignant process (excluding squamous cell or basal cell carcinoma of the
skin), unless that previous tumor was treated with curative intent and the patient has
been in remission for at least three years.

Patients with a history of seizures, encephalitis, or multiple sclerosis are not eligible.

Patients with known allergy to eggs are not eligible.

Patients should not have any cardiac disease, pulmonary disease, autoimmune disease, renal
disease or hepatic dysfunction that may be exacerbated by IL-2.