Vaccine Therapy With PROSTVAC/TRICOM and Flutamide Versus Flutamide Alone to Treat Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Sargramostim (GM-CSF, Leukine); Flutamide (Eulexin); PROSTVAC-F/ TRICOM; PROSTVAC-V/TRICOM
Intervention description: A recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) produced by recombinant deoxyribonucleic acid (DNA) technology in yeast Saccharomyces cerevisiae). Sargramostim is a 127 amino acid glycoprotein, altered from the native, natural human GM-CSF molecule; the position 23 arginine has been replaced with a leucine to facilitate the expression of the protein in yeast.; Orally administered, nonsteroidal, competitive antagonist of testosterone and other androgens at androgenic receptors and may alter the nuclear translocation of the androgen/receptor complex.; A recombinant fowlpox virus vector vaccine containing the genes for human PSA and three costimulatory molecules.; A recombinant vaccinia virus vector vaccine containing the genes for human prostatic specific antigen (PSA) and three co-stimulatory molecules.
Intervention MeSH terms: Metronidazole; Molgramostim; Flutamide; Sargramostim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 64.0
Sex: Male
Minimum age: 18 Years
Maximum age: 110 Years
Healthy volunteers: No
Keywords: Immunotherapy; Hormonal Therapy; Combination Therapy; Prostate Specific Antigen; Immunoassay; Prostate Cancer

Summary:

      Background:

        -  Flutamide is an approved drug for prostate cancer that blocks the effects of
           testosterone on prostate cancer cells and may slow the progression of the disease.

        -  The vaccine in this study consists of a priming vaccine called PROSTVAC (rilimogene
           galvacirepvec/rilimogene glafolivec) -V/TRICOM (triad of costimulatory molecules), made
           from vaccinia virus, and a boosting vaccine called PROSTVAC-F/TRICOM, made from fowlpox
           virus. DNA (Deoxyribonuceic acid) is inserted into the priming and boosting vaccine
           viruses to cause production of proteins that enhance immune activity and also to produce
           prostate specific antigen (PSA) a protein that is normally produced by the patients
           tumor cells.

        -  GM-CSF (granulocyte macrophage colony stimulating factor), given along with the vaccine,
           is a chemical that boosts the immune system. It is used in this study to try to increase
           the usefulness of the vaccine by increasing the number of immune cells at the
           vaccination site.

      Objectives:

      -To determine if treatment with a prostate cancer vaccine plus flutamide is more effective
      than flutamide alone in delaying disease progression in patients with prostate cancer.

      Eligibility:

        -  Patients 18 years of age and older with androgen-insensitive prostate cancer that has
           not spread beyond the prostate gland.

        -  Patients with a rising PSA (prostatic specific antigen) who have already been treated
           with anti-iandrogen therapy (either bicalutamide or nilutamide).

      Design:

        -  There are two treatment groups in this study. Group A receives only flutamide; group B
           receive flutamide plus vaccine.

        -  Patients in both groups receive flutamide by mouth three times a day.

        -  Patients in group B receive PROSTVAC-V/TRICOM on day 1 and PROSTVAC-F/TRICOM on day 29
           and again every 4 weeks. All vaccines are given as injections under the skin.

        -  Patients have blood tests for PSA levels every month and scans every 3 months until the
           disease worsens.

        -  After 3 months of therapy, patients receiving in group A (flutamide alone) may cross
           over to receive vaccine if they develop a rising PSA and scans show no sign of disease
           spread. Patients in group B (flutamide plus vaccine) stop flutamide and may continue
           vaccine therapy. At this point patients may continue to receive treatment until the
           disease progresses or PSA levels rise....
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        A. Histopathological documentation of prostate cancer confirmed in the Laboratory of
        Pathology at the: National Institutes of Health (NIH) Clinical Center prior to starting
        this study. If no pathologic specimen is available, patients may enroll with a pathologists
        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
        (prostatic specific antigen) with castrate levels of testosterone and no evidence of
        metastatic disease on CT (computed tomography) 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 (Eastern Cooperative Oncology Group) 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 (Hemoglobin) 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 (aspartate
        aminotransferase) and ALT (alanine aminotransferase) 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 (human immunodeficiency virus) 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.)