Human Telomerase Reverse Transcriptase Messenger RNA (hTERT mRNA) Transfected Dendritic Cell Vaccines

Primary objectives of trial include to evaluate the safety and biologic efficacy of hTERT mRNA transfected dendritic cells (DC), applied in a prime-boost format, to stimulate hTERT-specific CD4+ and CD8+ T-cell responses in subjects with metastatic prostate cancer. Secondary objectives include estimating objective clinical response, the duration of such responses, progression-free survival and overall survival among all subjects. The hTERT mRNA-transfected DC vaccine platform has previously been studied in several phase I/II trials and has demonstrated safety and bioactivity in subjects with metastatic prostate and renal cell carcinomas. The objective of this trial is to enhance the observed bioactivity of the vaccine by using a prime-boost strategy. This is an open label, uncontrolled safety and efficacy study. Subjects with metastatic prostate cancer will be eligible for this study and will receive 1x107 cells administered ID at study week 1,2,3,4,5, and 6 (Prime). Thereafter, subjects will be randomized with equal probability to receive either 5x106 cells administered ID at study week 10 followed by monthly immunizations (Treatment arm A) or 1x107 cells administered ID at study week 10 followed by monthly immunizations (Treatment arm B). The safety, biologic and clinical efficacy of each regimen will be analyzed. The study will be solely conducted at the University of Florida in Gainesville, FL. Subjects will be recruited through the oncology clinics of the Departments of Urology and Radiation Oncology. The vaccine will be manufactured in a dedicated GMP-compliant cell production facility located on the 4th floor of the Cancer Genetics Research Institute. Immunological testing will be performed in the Immunological Monitoring Core laboratory of the Department of Urology using standardized assay systems. Subjects with histologically or clinically confirmed metastatic prostate cancer (stages pT1-4, N0-3, M+) are eligible for this study. Subjects treated with medical hormone ablative therapy (LHRH analogues or estrogens) should continue to receive LHRH analogues only. In subjects receiving nonsteroidal medical hormonal treatment (i.e. flutamide or bicalutamide) and who are experiencing a rising PSA, a 4 week period of observation will be required following the discontinuation of the nonsteroidal antiandrogen prior to study entry. Subjects will be excluded from study if they have received chemotherapy or other forms of immunotherapy in the 4 weeks prior to study entry. They must not have a history of autoimmune disease, serious intercurrent chronic or acute illness, pulmonary disease, active hepatitis, serologic evidence for HIV, or be receiving corticosteroid or immunosuppressive therapy. All subjects must be older than 18 years. This is a randomized phase II clinical trial, in which up to 36 subjects will be randomized with equal probability to one of the two treatment arms. The objective of this trial is to decide which of the two treatment regimens should be selected for further testing. Hence, the primary objective of this trial is to select the arm with the highest biologic response and the first ranked arm will be selected for further study in a larger efficacy trial.