41 15.3 Treatments .......................................................................................................................... 41 15.4 Primary Objective ................................................................................................................ 41 15.4.1 Variable ....................................................................................................................... 41 15.4.2 Statistical Hypothesis, Model, and Method of Analysis ............................................... 41 15.4.3 Handling of missing values, censoring, and discontinuations ..................................... 43 15.5 Secondary Objective ........................................................................................................... 43 15.6 Exploratory Objectives ........................................................................................................ 43 15.7 Interim Analysis ................................................................................................................... 44 15.8 Sample Size Calculation ..................................................................................................... 44 16 ADMINISTRATIVE AND ETHICAL CONSIDERATIONS ........................................................... 44 16.1 Regulatory and Ethical Compliance .................................................................................... 44 16.2 DUHS Institutional Review Board and DCI Cancer Protocol Committee ............................ 44 16.3 Informed Consent ................................................................................................................ 44 16.4 Privacy, Confidentiality, and Data Storage ......................................................................... 45 16.5 Data and Safety Monitoring ................................................................................................. 45 16.6 Protocol Amendments ......................................................................................................... 46 16.7 Records Retention ............................................................................................................... 46 16.8 Conflict of Interest ............................................................................................................... 47 16.9 Costs to the Subject ............................................................................................................ 47 16.10 Registration Procedure ................................................................................................... 47 17 REFERENCES ............................................................................................................................ 48 18 APPENDICES ............................................................................................................................. 55 18.1 Protocol Synopsis and Summary ........................................................................................ 55 18.2 Special or Representative SOPs and FORMs .................................................................... 77 18.3 DSMBplus Monitoring Plan ................................................................................................. 78 18.4 Standard Radiation Therapy ............................................................................................... 79 18.5 Temozolomide Therapy ...................................................................................................... 80 18.5.1 Concurrent TMZ and RT ............................................................................................. 80 18.5.2 Guidelines for 21- day TMZ Therapy ........................................................................... 80 Pro00054746: RESIST Study Version: 20171011 PT-PhI-II v05.22.12 Duke Cancer Institute Page 5 CONFIDENTIAL 2 LIST OF FIGURES Figure 1. Study Schema ..............................................................................................................................