OBJECTIVES~This is a randomized, controlled trial that will test the hypothesis that replication-competent adenovirus-mediated suicide gene therapy in combination with 80 Gy intensity modulated radiotherapy (IRMT)will improve freedom from failure (FFF) relative to 80 Gy IMRT alone in patients with newly-diagnosed prostate cancer with an intermediate-risk profile.~The trial contains two treatment arms:~Arm 1- Gene Therapy + IMRT Arm 2- IMRT~The study will be stratified by clinical site and pre-treatment risk factors (e.g., % positive biopsy cores, Gleason score.~Gleason score 5/6 AND PSA <10 ng/mL; AND >=50% positive biopsy cores~(Gleason score 5/6 and PSA 10-20 ng/mL) OR (Gleason score 7 and PSA 0 - 20 ng/mL); AND <50% positive biopsy cores~Gleason score 5/6 and PSA 10-20 ng/mL) OR (Gleason score 7 and PSA 0-20 ng/mL) AND >=50% positive biopsy cores.~An interim safety analysis (Interim Analysis 1) will be conducted after the first 21 patients in the investigational therapy arm, and a total of 42 subjects in both arms, have completed the 90 day toxicity assessment following randomization (phase 2 component). If, at this point, there are no safety concerns as determined by the Data and Safety Monitoring Board (DSMB), the trial will continue as a phase 3 study with two additional interim analyses (Interim Analyses 2 & 3). The primary analysis for treatment efficacy will be based on all randomized subjects.~Primary~To assess the relative efficacy of replication-competent adenovirus-mediated suicide gene therapy in combination with 80 Gy intensity modulated radiotherapy (IMRT) versus 80 Gy IMRT alone in patients with newly-diagnosed prostate cancer with an intermediate-risk profile. The primary endpoint is freedom from failure (FFF) (biochemical or clinical).~Secondary~To assess the difference between the two treatment arms for:~Acute (<= 90 days) and long-term (> 90 days) toxicity.~Prostate biopsy status (12 cores) at 2 years.~Freedom from distant metastases.~Disease-specific and overall survival.~Quality of life.~Exploratory~To examine:~Possible effect of gene therapy on PSA doubling time (PSADT) after PSA failure.~Possible association between the primary and secondary outcomes and Ad5-yCD/mutTKSR39rep-ADP adenovirus persistence (as measured by adenoviral DNA in blood).~Possible association between the primary and secondary outcomes and specific immunological endpoints including levels of circulating CD4+ and CD8+ T lymphocytes, T-cell proliferation response, cytotoxic T lymphocyte (CTL) response, and development of antibodies to prostate-specific antigens.
This is a randomized, controlled trial that will test the hypothesis that replication-competent adenovirus-mediated suicide gene therapy in combination with 80 Gy intensity modulated radiotherapy (IRMT)will improve freedom from failure (FFF) relative to 80 Gy IMRT alone in patients with newly-diagnosed prostate cancer with an intermediate-risk profile.