Randomized Trial of Suicide Gene Therapy and Prostate Cancer

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.