0 Dead. NCI Protocol #: CITN12 -03 Version Date: July 26, 2017 55 APPENDIX B CTEP MULT ICENTER GUIDELINES If an institution wishes to collaborate with other participating institutions in performing a CTEP sponsored research protocol, then the following guidelines must be followed. Responsibility of the Protocol Chair  The Protocol Chair will be the single liaison with the CTEP Protocol and Information Office (PIO). The Protocol Chair is responsible for the coordination, development, subm ission, and approval of the protocol as well as its subsequent amendments. The protocol must not be rewritten or modified by anyone other than the Protocol Chair. There will be only one version of the protocol, and each participating institution will use that document. The Protocol Chair is responsible for assuring that all participating institutions are using the correct version of the protocol.  The Protocol Chair is responsible for the overall conduct of the study at all participating institutions and for monitoring its progress. All reporting requirements to CTEP are the responsibility of the Protocol Chair.  The Protocol Chair is responsible for the timely review of Adverse Events (AE) to assure safety of the patients.  The Protocol Chair will be resp onsible for the review of and timely submission of data for study analysis. Responsibilities of the Coordinating Center  Each participating institution will have an appropriate assurance on file with the Office for Human Research Protection (OHRP), NIH. The Coordinating Center is responsible for assuring that each participating institution has an OHRP assurance and must maintain copies of IRB approvals from each participating site.  Prior to the activation of the protocol at each participating institution, an OHRP form 310 (documentation of IRB approval) must be submitted to the CTEP PIO.  The Coordinating Center is responsible for central patient registration. The Coordinating Center is responsible for assuring that IRB approval has been obtained at each participating site prior to the first patient registration from that site.  The Coordinating Center is responsible for the preparation of all submitted data for review by the Protocol Chair.  The Coordinating Center will maintain documentation of AE reports. There are two options for AE reporting: (1) participating institutions may report directly to CTEP with a copy to the Coordinating Center, or (2) participating institutions report to the Coordinating Center who in turn report to CTEP. The Coordinating C enter will submit AE reports to the Protocol Chair for timely review.  Audits may be accomplished in one of two ways: (1) source documents and research records for selected patients are brought from participating sites to the Coordinating Center for audit, or (2) selected patient records may be audited on -site at participating sites. If the NCI chooses to have an audit at the Coordinating Center, then the Coordinating Center is responsible for having all source documents, research records, all IRB approval documents, NCI Drug Accountability Record forms, patient registration lists, response assessments scans, x -rays, etc. available for the audit. NCI Protocol #: CITN12 -03 Version Date: July 26, 2017 56 Inclusion of Multicenter Guidelines in the Protocol  The protocol must include the following minimum informati on:  The title page must include the name and address of each participating institution and the name, telephone number and e -mail address of the responsible investigator at each participating institution.  The Coordinating Center must be designated on the t itle page.  Central registration of patients is required. The procedures for registration must be stated in the protocol.  Data collection forms should be of a common format. Sample forms should be submitted with the protocol. The frequency and timing of data submission forms to the Coordinating Center should be stated.  Describe how AEs will be reported from the participating institutions, either directly to CTEP or through the Coordinating Center.  Describe how Safety Reports and Action Letters from CTEP w ill be distributed to participating institutions. Agent Ordering  Except in very unusual circumstances, each participating institution will order DCTD -supplied investigational agents directly from CTEP. Investigational agents may be ordered by a participating site only after the initial IRB approval for the site has bee n forwarded by the Coordinating Center to the CTEP PIO. NCI Protocol #: CITN12 -03 Version Date: July 26, 2017 57 APPENDIX C COCKCROFT -GAULT FOR MULA FOR CALCULATED CREATININE CLEARANCE This formula expects weight to be measured in kilograms and creatinine to be measured in mg/dL, as is standard in the USA. NCI Protocol #: CITN12 -03 Version Date: July 26, 2017 58 APPENDIX D DOSE ADJUSTMENT FOR OBESE PATIENTS Obesity is defined as a BMI > 30 (NHLBI Class 1 Obesity .) In order to determine the proper dose for patients classified as obese, an adjusted body weight is calculated. The following steps are provided to assist with the process: BMI Chart BMI 19 20 21 22 23 24 25 26 27 28 29 30 35 40 Ht Wt (lbs) 4'10" 91 96 100 105 110 115 119 124 129 134 138 143 167 191 4'11" 94 99 104 109 114 119 124 128 133 138 143 148 173 198 5'0" 97 102 107 112 118 123 128 133 138 143 148 153 179 204 5'1" 100 106 111 116 122 127 132 137 143 148 153 158 185 211 5'2" 104 109 115 120 126 131 136 142 147 153 158 164 191 218 5'3" 107 113 118 124 130 135 141 146 152 158 163 169 197 225 5'4" 110 116 122 128 134 140 145 151 157 163 169 174 204 232 5'5" 114 120 126 132 138 144 150 156 162 168 174 180 210 240 5'6" 118 124 130 136 142 148 155 161 167 173 179 186 216 247 5'7" 121 127 134 140 146 153 159 166 172 178 185 191 223 255 5'8" 125 131 138 144 151 158 164 171 177 184 190 197 230 262 5'9" 128 135 142 149 155 162 169 176 182 189 196 203 236 270 5'10" 132 139 146 153 160 167 174 181 188 195 202 207 243 278 5'11" 136 143 150 157 165 172 179 186 193 200 208 215 250 286 6'0" 140 147 154 162 169 177 184 191 199 206 213 221 258 294 6'1" 144 151 159 166 174 182 189 197 204 212 219 227 265 302 6'2" 148 155 163 171 179 186 194 202 210 218 225 233 272 311 6'3" 152 160 168 176 184 192 200 208 216 224 232 240 279 319 6.4” 156 164 172 180 189 197 205 213 221 230 238 246 287 328 NCI Protocol #: CITN12 -03 Version Date: July 26, 2017 59 If BMI > 30, p roceed with the following steps: 1. Determine Ideal Weight (1 kg = 2.2 lbs) : Males: 50 kg + (2.3 kg/inch over 5 feet) Females: 45.5 kg + (2.3 kg/inch over 5 feet) (Patients less than 5 feet: subtract 2.3 kg/inch ) 2. Determine Adjusted Body Weight: Ideal Weight + 0.25 (actual weight – ideal weight) = Adjusted Bo dy Weight Dose of CYT107 is 10 µg/kg. Vial is 1mg/0.5cc.