153Sm-EDTMP With or Without a PSA/TRICOM Vaccine To Treat Men With Androgen-Insensitive Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Samarium Sm 153 lexidronam pentasodium; Sargramostim; Recombinant vaccinia-TRICOM vaccine; Recombinant fowlpox-TRICOM vaccine
Intervention description: 1 mCi/Kg given intravenous (IV)over 1 minute on day 8.; 100 mcg/injection x 4 days given subcutaneously; 2 x 10^8 PFU given subcutaneously on day 1.; 1 x 10^9 PFU given subcutaneously on days 15 and 29
Intervention MeSH terms: Metronidazole; Samarium Sm-153 lexidronam; Vaccines; Sargramostim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 44.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Radionuclide; Immunotherapy; Radiation; PSA; Hormone Refractory Prostate Cancer; Prostate Cancer

Summary:

      Background:

        -  No treatment is known to improve survival for prostate cancer patients who have not been
           helped by previous treatments with hormones and chemotherapy.

        -  An experimental vaccine called prostate specific antigen (PSA)/TRICOM contains genes for
           a protein produced by prostate cancer cells called prostate-specific antigen (PSA). The
           vaccine can trigger the immune system to make cells that may be able to recognize and
           attack the cancer cells that make PSA.

        -  Granulocyte macrophage colony stimulating factor (GM-CSF) is an approved drug that is
           usually given to increase a patient's white blood cell count or to stimulate the immune
           system.

        -  1Samarium-153-ethylene diamine tetramethylene phosphonate (53Sm-EDTMP) is a radioactive
           drug that has been approved for many years to treat advanced prostate cancer. It is
           given through a vein and can be targeted directly to tumors in the bone where it can
           relieve pain caused by bone lesions. Radiation also increases the level of certain
           proteins inside the tumor, making it easier for the immune system to find and kill the
           tumor cells.

        -  When laboratory mice were given just vaccine, just radiation, or a combination of both,
           the combination was most effective in treating tumors.

      Objectives:

      -To determine if combined treatment with PSA/TRICOM vaccine and 153Sm-EDTMP radiation can
      delay progression of prostate cancer better than radiation alone.

      Eligibility:

      -Patients who have advanced prostate cancer that has worsened despite treatments with
      hormones, have two or more bone lesions related to their prostate cancer, and have had prior
      treatment with docetaxel chemotherapy.

      Design:

        -  Patients are randomly assigned to receive radiation alone (Arm A) or radiation with
           vaccine and sargramostim (Arm B).

        -  Arm A receives 153Sm-EDTMP radiation starting on study day 8 and repeated every 12
           weeks.

        -  Arm B receives a priming vaccine on study day 1 and radiation on day 8. Radiation
           therapy is repeated every 12 weeks. Boosting vaccines are given on days 15 and 29 and
           then monthly. GM-CSF is given with each vaccination (on the day of the vaccination and
           for the next 3 days) to enhance the immune response. Vaccinations and GM-CSF are given
           as injections under the skin, usually in the thigh. Radiation therapy is given through a
           vein.

        -  Patients are monitored regularly with physical examinations, blood and urine tests, and
           scans to evaluate safety and treatment response.

        -  Patients who are human leukocyte antigen serotype within HLA-A A serotype group
           (HLA-A2)-positive undergo apheresis, a procedure similar to donating blood, for
           obtaining immune cells called lymphocytes to measure the immune response to the vaccine.
    

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, National Institutes
        of Health (NIH), the National Naval Medical Center, or Walter Reed Army Medical Center; or
        participating Institute's Department of Pathology 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 metastatic castration resistant prostate cancer (CRPC) with at least 2 bone
        lesions consistent with prostate cancer metastasis and progressive disease (2 rising PSA
        values separated by at least one week, new or enlarging lesions consistent with prostate
        cancer, or clinical progression) on docetaxel for metastatic prostate cancer or inability
        to tolerate docetaxel.

        C. Life expectancy greater than or equal to 6 months.

        D. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

        E. No systemic steroid or steroid eye drop use within 2 weeks prior to initiation of
        experimental therapy.

        F. Hematological eligibility parameters (within 16 days of starting therapy).

          -  Granulocyte count greater than or equal to 1,500/mm^3

          -  Platelet (PLT) count greater than or equal to 100,000/mm^3

          -  Hemoglobin (Hgb) greater than or equal to 10 Gm/dL (Transfusion may be given to
             accomplish this)

        G. Biochemical eligibility parameters (within 16 days of starting therapy)

        -Hepatic function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less
        than 2.5 times upper limit of normal; bilirubin less than 1.5 mg/dL OR in patients with
        Gilbert's syndrome, a total bilirubin less than or equal to 3.0 mg/dL.

        H. No other active malignancies within the past 12 months (with the exception of
        nonmelanoma skin cancers or carcinoma in situ of the bladder and treated with curative
        intent) or life-threatening illnesses.

        I. Willing to travel to the National Institutes of Health (NIH) or participating Institute
        for follow-up visits.

        J. 18 years of age or greater.

        K. Able to understand and sign informed consent.

        L. Agree to use adequate contraception prior to study entry and for at least 4 months
        following the last vaccine injection.

        M. Patients must remain on medical castration therapy with testosterone-suppressing therapy
        (e.g., gonadotropin releasing hormone (GnRH) agonist), unless they have had surgical
        castration.

        N. Patients must have recovered from acute toxicities related to prior therapy or surgery.
        For chemotherapy, typically this is 3 to 4 weeks.

        O. Patients who are incontinent of urine should be willing to undergo bladder
        catheterization to minimize the risk of radioactive contamination of clothing, bed linen,
        and the patient's environment.

        P. Concurrent treatment with bisphosphonates is allowed. If bisphosphonates have been given
        within 2 weeks prior to planned (153)Sm-EDTMP, then a 99Tc whole-body scintigraphy (bone
        scan) will be performed to confirm uptake into lesions. Bisphosphonates will not be given
        within 48 hours after (153)Sm-EDTMP administration.

        Q. Serum creatinine less than or equal to 1.5 times 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, as listed below, of being immunocompromised:

          -  Human immunodeficiency virus (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.

        B. Patients should have no autoimmune diseases that have required treatment, such as
        Addison's disease, Hashimoto's thyroiditis, systemic lupus erythematosus, Sjogren's
        syndrome, scleroderma, myasthenia gravis, Goodpasture's syndrome, or active Grave's
        disease. Patients with a history of autoimmunity that has not required systemic
        immunosuppressive therapy or does not threaten vital organ function, including central
        nervous system (CNS), heart, lungs, kidneys, skin, and gastrointestinal tract (GI) tract,
        will be allowed.

        C. History of allergy or untoward reaction to prior vaccination with vaccinia virus or to
        any component of the vaccinia vaccine regimen. Note: prior vaccination with vaccinia is not
        required.

        D. Do not administer the recombinant vaccinia vaccine if the recipient 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), 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.

        E. 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.

        F. Patients with a history of cardiomyopathy or symptomatic congestive heart failure
        (unless stable on treatment), symptomatic arrhythmia not controlled by medication. Unstable
        atherosclerotic heart disease (e.g. unstable angina) who require active intervention and
        history of myocardial infarction or embolic stroke within the past 6 months.

        G. Patients with cardiac disease who 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, unless the
        underlying cause has been treated and patient has documented normal ejection fraction.

        I. Patients with pulmonary disease who have fatigue or dyspnea with ordinary physical
        activity are not eligible.

        J. Concurrent chemotherapy.

        K. No brain metastasis or history of seizures, encephalitis, or multiple sclerosis.

        L. Serious hypersensitivity reaction to egg products.

        M. Prior splenectomy.

        N. Contraindicated in patients who have known hypersensitivity to EDTMP or similar
        phosphonate compounds.

        O. Patients with symptomatic soft tissue disease or parenchymal disease will be excluded.

        P. Radiation therapy to bone within 4 weeks of study entry.

        Q. Patients previously treated with (153)Sm-EDTMP will be excluded.

        R. Patients requiring urgent local radiotherapy or orthopedic stabilization.