Docetaxel Followed by Provenge in Metastatic Prostate Cancer

Castration-resistant prostate cancer (CRPC) develops serial treatment resistance and is considered incurable. It is a largely indolent disease, which would give the body time to mount an effective immune response. CRPC is therefore potentially well suited for vaccine therapy. Docetaxel is an antineoplastic agent belonging to the taxoid family. The FDA-approved course of therapy for prostate cancer consists of 75 mg/m2 docetaxel given intravenously as a 1-hour infusion every 21 days on Day 1. Sipuleucel-T (Provenge), is an FDA-approved cancer vaccine therapy manufactured by culturing an individual's own freshly isolated peripheral blood mononuclear cells (PBMCs), including antigen-presenting cells (APCs) and T cells, with a fusion protein (PA-2024) composed of prostatic acid phosphatase (PAP) linked to granulocyte macrophage-colony stimulating factor (GM-CSF). A course of therapy consists of three doses of Provenge administered at 2-week intervals. This is an open-label phase II study in taxane-naïve patients with metastatic CRPC of docetaxel followed by Provenge. Adult (age \>18 years) men with metastatic CRPC. pathologically-confirmed adenocarcinoma of the prostate with clinical or radiologic evidence of metastatic disease that has progressed despite treatment with anti-androgens, inhibitors of adrenal-produced androgens (abiraterone), or androgen receptor inhibitors (enzalutamide), and who, prior to study entry are candidates to receive Standard of Care chemotherapy (e.g., docetaxel/prednisone) or immunotherapy (Provenge), will be enrolled in this study. This study will recruit a total of 32 patients with metastatic CRPC. Patients will receive 6 cycles of docetaxel followed by Provenge. Treatment will be administered on an outpatient basis. Patients must meet one of the following prognostic criteria: * PSA doubling time ≤6 months * \>10 bone lesions (only if they meet PSA doubling time criteria) * Visceral metastases * Bone and lymph node lesions The primary objective of this study is to characterize the immunological biomarkers during therapy and correlate the immunological biomarkers with clinical outcome. The strategy aims to determine whether cytokine production and T cell infiltration of tumor cells could favor regression using a combination of chemotherapy plus vaccine. Tissue endpoints will include biopsies prior to chemotherapy, on day 14 during the rest period between therapies and after vaccine therapy. Prostate cancer tissue infiltrates will be studied for expression of CD3, CD4, CD8, CD25/FOX3P, CD56, CTLA-4, PD-1, and Ki67. Additional immunological endpoints will be secondary antigen spread and various cytokine biomarkers.