Vaccine Plus Booster Shots in Men With Prostate Cancer Undergoing Treatment With Radical Prostatectomy
Condition: Prostate Cancer; Prostatic Neoplasms; Neoplasms, Prostate
MeSH terms: Prostatic Neoplasms; Neoplasms
Intervention: PROSTVAC-V/TRICOM; PROSTVAC-F/TRICOM
Intervention description: A recombinant vaccinia virus vector vaccine containing the genes for human prostatic specific antigen (PSA) and three co-stimulatory molecules.; A recombinant fowlpox virus vector vaccine containing the genes for human PSA and three co-stimulatory molecules.
Intervention MeSH terms: Metronidazole
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 27.0
Sex: Male
Minimum age: 18 Years
Maximum age: 100 Years
Healthy volunteers: No
Keywords: Surgery; Neoadjuvant; CD8 Cell Infiltrate Response; CD4 Cell Infiltrate Response; Vaccine

Summary:

      Background:

      - Some men with prostate cancer have their prostate glands removed. The cancer can still come
      back. Researchers want to know if receiving a vaccine before prostate removal surgery can
      lead to less recurrence.

      Objective:

      - To see if a vaccine and booster shots given to men with prostate cancer before surgery
      changes the immune cells in the prostate gland.

      Eligibility:

      - Men age 18 and older who have prostate cancer that has not spread, and who want to have
      their prostate glands removed as treatment.

      Design:

        -  Participants will be screened by their regular cancer care. They may have a small piece
           of prostate removed.

        -  Participants must practice effective birth control before and during the study treatment
           and for 1 month after the last vaccine booster.

        -  Participants will have a medical history, physical exam, and blood and liver tests. They
           will be asked about how they perform daily activities.

        -  Participants will have a magnetic resonance imaging (MRI) scan of the prostate. The
           scanner is a metal cylinder in a strong magnetic field. Participants will lie on a table
           that slides in and out of the scanner.

        -  Participants will be injected with the vaccine, most likely in the leg. They will be
           injected with the vaccine booster 3 times over several weeks.

        -  At each booster visit, participants will have a medical history, physical exam, and
           blood and liver tests.

        -  Participants will have another MRI. Then they will have surgery to remove their
           prostate.

        -  Participants will have 2 follow-up visits during the year after surgery. They will have
           a medical history, physical exam, and blood test.
    

Eligibility criteria:

        -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.