Vaccine Plus Booster Shots in Men With Prostate Cancer Undergoing Treatment With Radical Prostatectomy

Background

- Adenocarcinoma of the prostate is the most common cancer diagnosis in American males and
follows lung cancer as the leading cause of cancer death.

- Vaccine strategies represent a novel therapeutic approach in the treatment for prostate
cancer. One potential target for a prostate cancer vaccine is prostatic specific antigen
(PSA), due to its restricted expression on prostate cancer and normal prostatic
epithelial cells.

- A neoadjuvant approach may be of potential benefit providing prolonged protection via
the patient s immune system against future recurrence.

- PROSTVAC is a vaccine that induces strong immune responses, has shown promising evidence
of activity in a randomized phase II study (8.5 month improvement in median overall
survival) and is currently in phase III clinical testing.

- This vaccine has been tested in locally recurrent prostate cancer with substantial
inflammatory infiltrates within the prostate seen following subcutaneous and
intraprostatic injection.

Objectives

-The primary objective is to evaluate the post vaccine immunologic cluster of differentiation
4 (CD4) and cluster of differentiation 8 (CD8) cell infiltrate response of a neoadjuvant
vaccine strategy in prostatectomy specimens in patients who plan to undergo radical
prostatectomy.

Eligibility

- Patients must have biopsy proven prostate cancer and are surgical candidates for radical
prostatectomy

- Must be of sufficient good health to be surgical candidates for radical prostatectomy
and have elected radical prostatectomy for management of their prostate cancer

- Granulocyte count is greater than or equal to 1,500/mm(3), Platelet is greater than or
equal to 50,000/mm(3), hemoglobin (Hgb) is greater than or equal to 8 g/dL, Bilirubin <
1.5mg/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5x
upper limit of normal (ULN), Creatinine is less than or equal to 1.5 X ULN

- Pre-intervention biopsy tissue must be available either from outside institution or
repeat biopsy

Design

- This study will utilize rV-PSA(L155)-TRICOM (PROSTVAC-V) as a priming vaccination
followed by monthly boosting with rF-PSA (L155)-TRICOM (PROSTVAC-F) for 3 months.

- Patients will undergo radical prostatectomy after 4 months of treatment with
PROSTVAC-V/F.

- The maximum accrual to the trial will be 27 patients.

-INCLUSION CRITERIA

1. Patients must have histopathological documentation of adenocarcinoma of the prostate
prior to starting this study and evaluable biopsy tissue (e.g., unstained slides or
blocks) available for analysis. If evaluable tissue is not available, the patient must
agree to undergo a pre-vaccination prostate biopsy on study as an alternative to
having available tissue available.

2. Patients must be a surgical candidate for radical prostatectomy based on standard
workup of prostatic specific antigen (PSA), biopsy results, and if necessary
supplemental imaging.

3. Patients must have chosen radical prostatectomy as their definitive treatment of
choice for management of their prostate cancer.

4. Patients must have a performance status of 0 to 1 according to the Eastern Cooperative
Oncology Group (ECOG) criteria

5. No systemic steroid or steroid eye drop use within 2 weeks prior to initiation of
experimental therapy. Limited doses of systemic steroids to prevent intravenous (IV)
contrast, allergic reaction or anaphylaxis (in patients who have known contrast
allergies) are allowed.

6. Hematological eligibility parameters (within one month of starting therapy):

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

- Platelet count greater than or equal to 50,000/mm(3)

- Hemoglobin (Hgb) greater than or equal to 8 g/dL

7. Biochemical eligibility parameters (within one month of starting therapy):

1. Hepatic function: Bilirubin < 1.5 mg/dl (OR in patients with Gilbert's syndrome,
a total bilirubin less than or equal to 3.0 mg/dL), aspartate aminotransferase
(AST) and alanine aminotransferase (ALT) < 2.5 times upper limit of normal.-.
Creatinine less than or equal to 1.5 X ULN

2. Creatinine less than or equal to 1.5 X ULN

3. Patients must be test negative for human immunodeficiency virus (HIV), Hepatitis
B and C.

8. Patients must not have other active invasive malignancies within the past 2 years
(with the exception of non-melanoma skin cancers) or life threatening illnesses.

9. Patients must be willing to travel to the study site for follow-up visits.

10. Patients must be greater or equal to18 years of age.

11. All patients who have received prior vaccination with vaccinia virus (for smallpox
immunization) must not have a history of allergy to the vaccine.

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

13. The effects of the study agents used in this protocol on the developing human fetus
are unknown. For this reason men must agree to use adequate contraception
(abstinence,vasectomy, or female partner use of intrauterine device (IUD), hormonal
[birth control pills, injections, or implants], tubal ligation) prior to study entry
and for up to one month after the last vaccination.

EXCLUSION CRITERIA

1. Prior splenectomy.

2. The recombinant vaccinia vaccine should not be administered if the following apply to
either recipients or, for at least 3 weeks after vaccination, their close household
contacts (Close household contacts are those who share housing or have close physical
contact):

- 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 under 3 years of age

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

- HIV positivity due to the potential for decreased tolerance and risk for severe
side effects.

- Hepatitis B or C positivity.

- Concurrent use of topical steroids (including steroid eye drops) or systemic
steroids. This is to avoid immunosuppression which may lead to potential
complications with vaccinia (priming vaccination). Nasal or inhaled steroid use
is permitted.

3. Patients with known allergy to eggs.

4. Other serious intercurrent illness.

5. Patients with a history of unstable or newly diagnosed angina pectoris, recent
myocardial infarction (within 6 months of enrollment) or New York Heart Association
class II-IV congestive heart failure.

6. Patients with significant autoimmune disease that is active or potentially life
threatening if activated.

7. Patients with clinically significant cardiomyopathy requiring treatment.