title: Randomized phase II trial of docetaxel with or without PSA-TRICOM vaccine in patients with castrate-resistant metastatic prostate cancer: A trial of the ECOG-ACRIN cancer research group (E1809).
abstract: Anti-tumor vaccines have demonstrated efficacy in patients with castration-resistant metastatic prostate cancer. One vaccine, Prostvac-VF®, using a heterologous prime-boost strategy with vaccinia and fowlpox viral vectors encoding PSA, is currently being evaluated in a registration phase III multinational clinical trial. The current trial was planned to assess the clinical efficacy of this vaccine in patients with castration-resistant metastatic prostate cancer receiving subsequent docetaxel chemotherapy. 10 patients with metastatic castration-resistant prostate cancer, with a predicted survival of at least 18 months, were enrolled out of a planned 144 patients. Eight of 10 patients were treated and were randomized to receive docetaxel chemotherapy alone (Arm B, n = 2) versus treatment with Prostvac-VF (days 1, 15, 29, 43, 57) followed by docetaxel (Arm A, n = 6) chemotherapy beginning at month 3. The primary endpoint of the trial was overall survival, and secondary endpoints included time to radiographic progression and immunological response. The trial was opened within the Eastern Cooperative Oncology Group, but due to slow accrual was closed by CTEP after only 10 patients were enrolled within 13 months.
  
  
  RESULTS
  Presented here are the safety, clinical, and immunological results from 8 eligible patients who underwent treatment. Two of 6 patients treated on Arm A, with vaccine followed by docetaxel, had a >50% PSA response, with one of these patients experiencing a PSA decline during treatment with vaccine. Significant PSA-specific CD4+ and CD8+ T-cell responses and IgG antibody responses specific for PSA were not detected. The primary endpoint of overall survival cannot be assessed due to limited accrual. The lack of T-cell responses, even in this small cohort, suggests that further validation and development of immune biomarkers will be important for future studies. Other trials remain ongoing to evaluate the role of anti-tumor vaccination in sequence with other traditional anti-tumor therapies.
authors.affiliation: a University of Wisconsin Carbone Cancer Center ; Madison , WI USA.
authors.forename: Douglas G
authors.initials: DG
authors.lastname: McNeel
authors.affiliation: b Dana Farber Cancer Institute ; Boston , MA USA.
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Chen
authors.affiliation: c National Cancer Institute ; Bethesda , MD USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Gulley
authors.affiliation: a University of Wisconsin Carbone Cancer Center ; Madison , WI USA.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Dwyer
authors.affiliation: c National Cancer Institute ; Bethesda , MD USA.
authors.forename: Ravi A
authors.initials: RA
authors.lastname: Madan
authors.affiliation: d Johns Hopkins University School of Medicine ; Baltimore , MD USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Carducci
authors.affiliation: e Rutgers Cancer Institute of New Jersey ; New Brunswick , NJ USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: DiPaola
mesh_terms: D000368:Aged; D000912:Antibodies, Neoplasm / Q000097:blood; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D000077143:Docetaxel; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000097:blood / Q000276:immunology; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D007074:Immunoglobulin G; C588274:PROSTVAC; D043823:Taxoids; D000077143:Docetaxel; D017430:Prostate-Specific Antigen
keywords: docetaxel; phase II clinical trial; prostate cancer; vaccine