A Randomized, Double-blind, Phase 3 Efficacy Trial of PROSTVAC-V/F +/- GM-CSF in Men With Asymptomatic or Minimally Symptomatic Metastatic Castrate-Resistant Prostate Cancer
Condition: Prostate Cancer Metastatic
MeSH terms: Prostatic Neoplasms
Intervention: PROSTVAC-V; PROSTVAC-F; GM-CSF; GM-CSF Placebo; Placebo
Intervention description: PROSTVAC V/F Placebo
Intervention MeSH terms: Molgramostim; Sargramostim
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1297.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: PROSTVAC; metastatic; prostate cancer; castrate-resistant; vaccine; immunotherapy; Phase 3

Summary:

      The purpose of this study is to determine whether PROSTVAC alone or in combination with
      GM-CSF is effective in prolonging overall survival in men with few or no symptoms from
      metastatic, castrate-resistant prostate cancer.
    

Eligibility criteria:

        Inclusion Criteria:

        Men, ≥18years of age with documented asymptomatic or minimally symptomatic metastatic
        castration-resistant prostate cancer.

        Documented progressive disease post surgical castration or during androgen suppression
        therapy, or during complete androgen blockade therapy and withdrawal. Documented by either
        criterion a (Radiological progression), OR criterion b (PSA progression).

          1. Radiological progression defined as any new/enlarging bone metastases or new/enlarging
             lymph node disease, consistent with prostate cancer.

             OR

          2. PSA progression defined by sequence of rising values separated by > 1 week (2 separate
             increasing values) over a threshold minimum of 2.0 ng/ml. (PCWG2 PSA eligibility
             criteria).

        Chemotherapy naïve and Vaccinia-experienced (previous smallpox vaccination). Currently
        using a GnRH agonist or antagonist (unless surgically castrated).

        Exclusion Criteria:

        Cancer-related pain requiring scheduled opioid narcotics for control (as needed, ≤ 2x per
        week is allowed).

        Metastasis to organ systems other than lymph nodes and/or bone. Estimated PSA doubling time
        of <1 month as established within 6 months of the anticipated first dose of vaccine or
        placebo.

        Concurrent or prior Provenge (sipuleucel-T) immunotherapy for prostate cancer. Receipt of
        an investigational agent within 30 days (or 60 days for an antibody-based therapy) of the
        first planned dose of PROSTVAC-V/F.

        History of prior malignancies other than prostate cancer within the past 3 years, excluding
        successfully resected basal or squamous cell carcinoma of the skin.

        Congestive heart failure (NYHA Class II, III, or IV), unstable angina, ventricular or
        hemodynamically significant atrial arrhythmia, or cardiovascular disease such as stroke or
        myocardial infarction (current or within the past 6 months) Confirmed positive for HIV,
        hepatitis B, and /or hepatitis C. Immunodeficiency or splenectomy. History of or active
        autoimmune disease, persons with vitiligo are not excluded. Diabetics are not excluded if
        the condition is well controlled.

        History of atopic dermatitis or active skin condition (acute, chronic, exfoliative) that
        disrupts the epidermis.