A Randomized Phase II Trial Combining Vaccine Therapy With PROSTVAC/TRICOM and Flutamide vs. Flutamide Alone in Men With Androgen Insensitive, Non-Metastatic (D0.5) Prostate Cancer

Inclusion Criteria

- INCLUSION CRITERIA:

A. Histopathological documentation of prostate cancer confirmed in the Laboratory of
Pathology at the: NIH Clinical Center prior to starting this study. If no pathologic
specimen is available, patients may enroll with a pathologist's report showing a
histologic diagnosis of prostate cancer and a clinical course consistent with the disease.

B. Must have non-metastatic androgen insensitive prostate cancer with a rising PSA with
castrate levels of testosterone and no evidence of metastatic disease on CT scan or bone
scan. A rising PSA is defined as two consecutively rising PSA levels, separated by at
least 1 month apart, with the last measurement that is greater than 1ng/ml. Patients on
nilutamide therapy must undergo nilutamide withdrawal for at least 4 weeks and still show
evidence of a rising PSA. Following treatment with bicalutamide, patients must undergo
withdrawal for at least 6 weeks and still show evidence of a rising PSA.

C. Life expectancy greater than or equal to 6 months.

D. ECOG performance status of 0-1.

E. No systemic steroid or steroid eye drop use within 2 weeks prior to initiation of
experimental therapy.

F. Hematological eligibility parameters:

- Granulocyte count greater than or equal to 1,500/mm(3).

- Platelet count greater than or equal to 100,000/mm(3)

- Hgb greater than or equal to 9 Gm/dL

- Lymphocyte count greater than or equal to 500/mm(3).

G. Biochemical eligibility parameters (within 16 days of starting therapy)

-Hepatic function: Bilirubin less than or equal to 1.5 mg/dl, OR patients with Gilbert's
syndrome, a total bilirubin less than or equal to 3.0 mg/dL, AST and ALT less than 2.5
times upper limit of normal

H. No other active malignancies within the past 3 years (with the exception of
non-melanoma skin cancers or carcinoma in situ of the bladder) or life threatening
illnesses.

I. Willing to travel to the NIH for follow-up visits.

J. 18 years of age or greater.

K. Able to understand and sign informed consent.

L. Must agree to use effective birth control (such as a condom) or abstinence during and
for a period of 4 months after the last vaccination therapy. Patients must be willing to
remain on chemical castration therapy, unless they have had surgical castration.

M. Patients must have recovered from acute toxicities related to prior therapy or surgery.

N. Parameters for assessment of baseline renal function:

Serum creatinine less than or equal to 1.5 times the upper limit of normal OR creatinine
clearance on a 24-h urine collection of greater than or equal to 60 mL/min.

EXCLUSION CRITERIA:

A. Patients should have no evidence of being immunocompromised as listed below.

- Human immunodeficiency virus positivity due to the potential for decreased tolerance
and may be at risk for severe side effects.

- Concurrent use of topical steroids (including steroid eye drops) or systemic
steroids. Nasal or inhaled steroid use is permitted.

- Patients who have undergone allogenic peripheral stem cell transplantation or solid
organ transplantation requiring immunosuppression.

B. Patients who test positive for active Hepatitis B or Hepatitis C infection.

C. Patients should have no autoimmune diseases that have required treatment such as,
Addison's disease, Hashimoto's thyroiditis, or systemic lupus erythematous, Sjogren
syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome, active Grave's disease.

D. History of allergy or untoward reaction to prior vaccination with vaccinia virus or to
any component of the vaccinia vaccine regimen.

E. Do not administer the recombinant vaccinia vaccine if the recipient, or for at least
three weeks after vaccination, their close household contacts (close household contacts
are those who share housing or have close physical contact) are: 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 wounds) until condition resolves; pregnant or nursing
women; children 3 years of age and under; and immunodeficient or immunosuppressed persons
(by disease or therapy), including HIV infection.

F. Serious intercurrent medical illness (e.g., one that requires treatment) which would
interfere with the ability of the patient to carry out the treatment program, including,
but not limited to, inflammatory bowel disease, Crohn's disease, ulcerative colitis, or
active diverticulitis.

G. Patients with cardiac disease that have fatigue, palpitation, dyspnea or angina with
ordinary physical activity (New York Heart Association class 2 or greater) are not
eligible.

H. Patients with a history of congestive heart failure or who have objective evidence of
congestive heart failure by physical exam or imaging are not eligible.

I. Patients with pulmonary disease that have fatigue or dyspnea with ordinary physical
activity are not eligible.

J. Concurrent chemotherapy.

K. No known brain metastasis, or with a history of seizures, encephalitis, or multiple
sclerosis.

L. Patients with a serious hypersensitivity reaction to egg products are not eligible.

M. Prior splenectomy.

N. Patients who have received prior flutamide therapy in the last year. (Patients treated
with flutamide in the neoadjuvant or adjuvant setting or those previously treated with
flutamide who did not have a rising PSA on treatment would be allowed to enroll on the
protocol.)