Enzalutamide in Combination With PSA-TRICOM in Patients With Non-Metastatic Castration Sensitive Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: PROSTVAC-F (Fowlpox)/TRICOM; PROSTVAC-V (Vaccinia)/TRICOM; Enzalutamide (Xtandi)
Intervention description: A recombinant fowlpox virus vector vaccine containing the genes for human prostate specific antigen (PSA) and three co-stimulatory molecules.; A recombinant vaccinia virus vector vaccine containing the genes for human prostate specific antigen (PSA) and three co-stimulatory molecules.; An androgen receptor inhibitor.
Intervention MeSH terms: Metronidazole
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 38.0
Sex: Male
Minimum age: 18 Years
Maximum age: 100 Years
Healthy volunteers: No
Keywords: Gene Transfer; Androgen Receptor Antagonist; PSA; Immune Response; Immunotherapy

Summary:

      Background:

      - Enzalutamide is a well tolerated hormone therapy that is used to treat advanced prostate
      cancer. It is given to help kill cancer cells and limit cancer cell growth. A new possible
      way of treating prostate cancer is using a therapeutic cancer vaccine (immune stimulating
      therapy) that may help activate the immune system against the cancer. The immune stimulating
      vaccine will help white blood cells recognize and kill the cancer cells throughout the body.
      This vaccine therapy has been tested in hundreds of patients and is very well tolerated.
      Researchers want to see whether this vaccine, given with enzalutamide, is more effective at
      treating advanced prostate cancer than enzalutamide alone.

      Objectives:

      - To compare the safety and effectiveness of enzalutamide with and without vaccine therapy
      for advanced prostate cancer.

      Key Eligibility:

        -  Men at least 18 years of age who have advanced castration sensitive prostate cancer.

        -  Patients must have testosterone within the normal range

        -  No evidence of metastatic prostate cancer on computed tomography (CT) or Bone scan

        -  No history of autoimmune diseases

        -  No previous immunotherapy within 3 years

      Design:

        -  Participants will be screened with a physical exam and medical history. Blood and urine
           samples will be collected. Imaging studies will be used to monitor the cancer before
           treatment.

        -  Participants will be separated into two groups. One group will have enzalutamide and the
           study vaccine. The other group will have enzalutamide alone.

        -  All participants will take enzalutamide once a day. They will take the drug for 3
           months. This form of intermittent therapy is common in this population of patients.

        -  The vaccine group of participants will receive the new study vaccine. They will have a
           single injection on the first day of the first study cycle. There will be regular
           booster injections afterward. There will be one injection during the third week of
           treatment, and one in the fifth week. The vaccine will then be given every 4 weeks until
           21 weeks have passed.

        -  Treatment will be monitored with frequent blood tests and imaging studies.
    

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, or Walter Reed
        National Military Medical Center prior to enrollment. 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. Biochemical progression defined as follows:

          -  For patients following definitive radiation therapy: a rise in prostate-specific
             antigen (PSA) of greater than or equal to 2 ng/mL above the nadir (per Radiation
             Therapy Oncology Group (RTOG)-American Society for Therapeutic Radiology and Oncology
             (ASTRO) consensus criteria).

          -  For patients following radical prostatectomy: rising PSA after surgical procedure.
             (Patients must have a PSA greater than or equal to 2ng/ml)

        C. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (Karnofsky greater
        than or equal to 80%).

        D. Patients must have a PSA doubling time of 12 months or less.

        E. Patients must have a rising PSA as confirmed by 3 values done at least 1 week apart and
        over no less than 1 month.

        F. Recovery from acute toxicity related to prior therapy, including surgery and radiation,
        or no toxicity greater than or equal to grade 2.

        G. Negative computed tomography (CT) scan/magnetic resonance imaging (MRI) and bone scan
        for metastatic prostate cancer.

        H. Hematological eligibility parameters (within 16 days before starting therapy):

        Granulocyte count greater than or equal to 1000/mm(3)

        Platelet count greater than or equal to 100,000/mm(3)

        Hemoglobin (Hgb) greater than or equal to 10 g/dL

        I. Biochemical eligibility parameters (within 16 days before starting therapy):

        Hepatic function: bilirubin less than or equal to 1.5 mg/dL (OR in patients with Gilbert's
        syndrome, a total bilirubin less than or equal to 3.0), aspartate transaminase (AST) and
        alanine transaminase (ALT) less than or equal to 2.5 times upper limit of normal.

        J. No other active malignancies within the past 36 months (with the exception of
        nonmelanoma skin cancers or carcinoma in situ of the bladder) or life-threatening illnesses

        K. Willing to travel to the National Institutes of Health (NIH) for follow-up visits.

        L. 18 years of age or older.

        M. Able to understand and sign informed consent.

        N. Baseline testosterone greater than or equal to lower limit of normal.

        O. PSA less than or equal to 20 ng/mL.

        P. The effects of enzalutamide, PSA-TRICOM or the combination on the developing human fetus
        are unknown. For this reason, men must agree to use adequate contraception (hormonal or
        barrier method of birth control; abstinence) prior to study entry and for the duration of
        study participation. Should a woman become pregnant or suspect she is pregnant while her
        partner is participating in this study, she should inform her treating physician
        immediately.

        EXCLUSION CRITERIA:

        A. Immunocompromised status due to:

          -  Human immunodeficiency virus (HIV) positivity.

          -  Active autoimmune diseases such as Addison's disease, Hashimoto s thyroiditis,
             systemic lupus erythematosus, Sjogren syndrome, scleroderma, myasthenia gravis,
             Goodpasture syndrome or active Graves 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 (GI) tract will be allowed.

          -  Other immunodeficiency diseases

        B. Chronic administration (defined as daily or every other day for continued use greater
        than 14 days) of corticosteroids deemed systemic by investigator within 28 days before the
        first planned dose of PSA-TRICOM. Use of inhaled steroids, nasal sprays, and topical creams
        for small body areas is allowed.

        C. Serious intercurrent medical illness that, in the judgment of the investigator, would
        interfere with patient's ability to carry out the treatment program.

        D. History of seizure, including any febrile seizure, loss of consciousness, or transient
        ischemic attack, or any condition that may pre-dispose to seizure (e.g., prior stroke,
        brain arteriovenous malformation, head trauma with loss of consciousness requiring
        hospitalization).

        E. Other medications used for urinary symptoms including 5-alpha reductase inhibitors
        (finasteride and dutasteride) and alternative medications known to alter PSA (eg
        phytoestrogens and saw palmetto)

        F. History of prior chemotherapy

        G. History of prior immunotherapy within the last 3 years

        H. Major surgery within 4 weeks prior to enrollment (Day 1 visit).

        I. History of allergic reactions attributed to compounds of similar chemical or biologic
        composition to enzalutamide or poxviral vaccines (e.g., vaccinia vaccine)

        J. Known allergy to eggs, egg products, aminoglycoside antibiotics (for example, gentamicin
        or tobramycin).

        K. History of atopic dermatitis or active skin condition (acute, chronic, exfoliative) that
        disrupts the epidermis

        L. Previous serious adverse reactions to smallpox vaccination

        M. Unable to avoid close contact or household contact with the following highrisk
        individuals for three weeks after the Day 1 vaccination: (a) children 3 years of age, (b)
        pregnant or nursing women, (c) individuals with prior or concurrent extensive eczema or
        other eczematoid skin disorders, or (d) immunocompromised individuals, such as those with
        human immunodeficiency virus (HIV).

        N. Receipt of an investigational agent within 30 days (or 60 days for an antibody based
        therapy) before the first planned dose of study drugs.

        O. Patients who test positive for Hepatitis B virus (HBV) or hepatitis C virus (HCV)

        P. Use of herbal products that may decrease PSA levels (e.g. saw palmetto)

        Q. Any gastrointestinal disease that could hinder the absorption of enzalutamide

        R. Uncontrolled hypertension (Systolic Blood Pressure (SBP)>170/ Diastolic Blood Pressure
        (DBP)>105)