Prostvac in Patients With Biochemically Recurrent Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: PROSTVAC -V; PROSTVAC-F
Intervention description: Recombinant Vaccinia Virus Vector Vaccine of the Genus Orthopoxvirus; Recombinant Fowlpox Virus Vector Vaccine of the Genus Avipoxvirus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 97.0
Sex: Male
Minimum age: 18 Years
Maximum age: 100 Years
Healthy volunteers: No
Keywords: Vaccine; PSA; Surveillance; Immunotherapy

Summary:

      Background:

      Some people who have been treated for prostate cancer still have high prostate-specific
      antigen (PSA) levels. This may indicate cancer. These people have non-metastatic castration
      sensitive prostate cancer (nmCSPC) or biochemical recurrent prostate cancer. Researchers
      think the immune system can be taught to fight and kill cancer cells. They think an
      immunotherapy vaccine called prostvac could help reduce PSA levels in people with this type
      of prostate cancer.

      Objective:

      To test if prostvac can decrease tumor growth rate as measured by PSA compared to getting
      surveillance alone.

      Eligibility:

      Men ages 18 or older who have nmCSPC or biochemical recurrent prostate cancer

      Design:

      Participants will be screened with:

      Medical history

      Physical exam

      Blood and urine tests

      Bone scan

      Computed tomography (CT) scan, or magnetic resonance imaging (MRI) and positron emission
      tomography (PET) scan: They lie in a machine that takes pictures of the body.

      Electrocardiogram: Soft electrodes are stuck to the skin to record heart signals.

      Participants will be part of 1 of 2 arms: Arm A will get prostvac for 6 months. Arm B will
      have surveillance for 6 months followed by prostvac for 6 months.

      During the prostvac period, participants will get prostvac as a shot under the skin on weeks
      1, 3, and 5, and then monthly for a total of 5 months.

      Participants will have follow-up visits at least every month until they recover from prostvac
      side effects or their cancer worsens. Visits may include repeats of screening tests.

      Participants will be followed for up to 15 years. They will have a physical exam every year
      for the first 5 years. They will have phone calls once a year.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

          -  Histopathological documentation of prostate cancer confirmed in either the Laboratory
             of Pathology at the National Institutes of Health (NIH) Clinical Center, Walter Reed
             National Military Medical Center, Memorial Sloan Kettering Cancer Center (MSKCC),
             Dana-Farber Cancer Institute (DFCI) or Beth Israel Deaconess Medical Center (BIDMC)
             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.

          -  Biochemical progression after definitive radiation or surgery defined as follows:

               -  For patients following definitive therapy: a rise in prostate-specific antigen
                  (PSA) of greater than or equal to 2ng/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 0.8 ng/ml)

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 1 (Karnofsky greater
             than or equal to 80%).

          -  Patients must have a PSA doubling time of 5-15 months.

          -  Patients must have a rising PSA as confirmed by 3 values done at least 1 week apart
             and over no less than 1 month.

          -  Recovery from acute toxicity related to prior therapy, including surgery and
             radiation, or no toxicity greater than or equal to grade 2.

          -  Negative computed tomography (CT) scan/magnetic resonance imaging (MRI) and bone scan
             for metastatic prostate cancer.

          -  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 10g/dL

          -  Biochemical eligibility parameters (within 16 days before starting therapy):

             --Hepatic function: bilirubin less than or equal to 1.5mg/dL (OR in patients with
             Gilbert's syndrome normal.

          -  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, in the opinion of the investigator

          -  Willing to travel to the National Institutes of Health (NIH), MSKCC, DFCI, BIDMC for
             follow-up visits.

          -  18 years of age or older.

          -  Able to understand and sign informed consent.

          -  Baseline testosterone greater than or equal to 100 ng/dl

          -  PSA less than or equal to 30 ng/mL.

          -  The effects PROSTVAC 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, for the duration of study therapy and at least one
             month post therapy. 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:

          -  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 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 (GI) tract will be allowed.

               -  Other immunodeficiency diseases

               -  Splenectomy

          -  Chronic administration (defined as daily or every other day for continued use > 14
             days) of corticosteroids deemed systemic by investigator within 28 days before the
             first planned dose of PROSTVAC. Use of inhaled steroids, nasal sprays, intra-articular
             injections and topical creams for small body areas is allowed.

          -  Serious intercurrent medical illness that, in the judgment of the investigator, would
             interfere with patient s ability to carry out the treatment program.

          -  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)

          -  History of prior chemotherapy

          -  History of prior immunotherapy within the last 3 years

          -  Major surgery within 4 weeks prior to enrollment (Day 1 visit).

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to poxviral vaccines (e.g., vaccinia vaccine)

          -  Known allergy to eggs, egg products, aminoglycoside antibiotics (for example,
             gentamicin or tobramycin).

          -  History of atopic dermatitis or active skin condition (acute, chronic, exfoliative)
             that disrupts the epidermis

          -  Previous serious adverse reactions to smallpox vaccination

          -  Unable to avoid close contact or household contact with the following high-risk
             individuals for three weeks after the Day 1 vaccination: Day 1 vaccination: (a)
             children less than or equal to 3 years of age, (b) pregnant or nursing women, (c)
             individuals with current or extensive eczema or other eczemoid skin disorders, or (d)
             immunocompromised individuals, such as those with HIV.

          -  Receipt of an investigational agent within 28 days (or 56 days for an antibody-based
             therapy) before the first planned dose of study drugs.

          -  Patients who test positive for hepatitis B virus (HBV) or hepatitis C virus (HCV)

          -  Uncontrolled hypertension (systolic blood pressure (SBP)>170/ DBP>105)

          -  Recruitment Strategies

        This study will be listed on available websites (www.clinicaltrials.gov,

        https://ccr.cancer.gov/clinical-trials-search-start) and participants will be recruited
        from the current patient population at NIH.