The reason for this design is due to the nature of the research intervention and is explained below. Enrollment will not stop unless stopping rules based on toxicity are satisfied: “After the third vaccine dose is administered, toxicity will be evaluated 90 days into the trial” Due to the nature of the research intervention, anti -tumor activity will be potentially delayed and the primary efficacy endpoint will be determined 18 to 20 months after initial patient accrual. Since we will be able to assess PSADT after nearly 20 months into the study, it will be unreasonable to stop the study due to unsatisfactory results prior to that point. This is the main reason why we will carry a one-stage design for the primary endpoint and a two-stage design for toxicity. Criteria for proceeding with enrollment into a subsequent stage prior to the two-year efficacy evaluation will be based on assessment of toxicity in the patient cohorts since this can be done as early as 90 days into the trial. For toxicity purposes, we will test the null hypothesis that the toxicity level is less than 15% versus the alternative that it is greater than 35%. The trial will be stopped whenever the null hypothesis is rejected. We will conduct these tests in 2 different looks —one after an enrolment of 17 subjects and the second after 25 subjects are enrolled. If 5 out of 17 show grade 3 vaccine-related toxicity or higher, the trial will stop (this will correspond to testing the toxicity hypotheses at level alpha=0.05 with a power 77%); otherwise, an additional 8 subjects will enter the trial. If 7 out of 25 show a grade 3 toxicity or if 2 out of 17 show a grade 4 toxicity or higher, the trial will stop (this will be equivalent to testing the toxicity hypotheses at l evel alpha =0.05 with a power 82%); otherwise we will proceed to full registration. The overall type I error for this test is 0.09. In addition, the trial will stop if any vaccine-related deaths occur. The determination of a death related to the vaccine will be made by the clinical trial team and an audit by the Data and Safety Monitoring Board. The reasons for using different looks at toxicity level is because we are using surrogate endpoints that had not been proven formerly to have an ease of predictability of an outcome of direct relevance to patients; also, it is not quite clear how theses surrogates relate to the pathway of the natural disease and to overall survival rate. Simon, Richard. “Optimal Two-Stage Designs for Phase II Clinical Trials,” Controlled Clinical Trials, 1989, Volume 10, pages 1-10. De Gruttola Victor et Al., “Considerations in the Evaluation of Surrogate Endpoints in Clinical Trials: Summary of NIH workshop” Controlled Clinical Trials, 2001, Volume 22, pages 485-502 Lubaroff Ad/PSA Phase II, protocol #2, page 30 Addendum PHASE II STUDY OF ADENOVIRUS/PSA VACCINE IN MEN WITH HORMONE - REFRACTORY PROSTATE CANCER Food and Drug Administration (FDA) Investigational New Drug (IND) #9706 Department of Defense, Prostate Cancer Research Program A-14059.2 The following are reporting requirements and responsibilities of the Principal Investigator to the United States Army Medical Research and Materiel Command’s (USAMRMC) Office of Research Protections (ORP), Human Research Protection Office ( HRPO). 1.