ACRIN Abdominal Committee ACRIN Gynecologic Committee Fall Meeting 2010

ACRIN Abdominal Committee ACRIN Gynecologic Committee CT Perfusion Study of Ovarian Cancer ACRIN 6695 Project Team

ACRIN Gynecologic Committee Study Schedule Cycle 1 (All cycles 3 weeks in length) Carboplatin AUC 6 IV day 1 every cycle x 6 cycles Paclitaxel 80 mg/m 2 IV days 1, 8 and 15 every cycle x 6 cycles Ovarian cancer: suboptimally debulked (e.g. > 1 cm tumor left behind Surgically) Cycle 1 (All cycles 3 weeks in length) Baseline RECIST CT scan & Perfusion CT Baseline (T0) At least 3 weeks post surgery and within 4 weeks prior to initiating protocol chemotherapy Carboplatin AUC 6 IV day 1 every cycle x 6 cycles Regimen I: Regimen II: Bevacizumab 15 mg/kg IV day 1 every cycle starting cycle 2 and continuing beyond cycle 6 until progression or adverse effects preclude further treatment RANDOMIZERANDOMIZE Follow-up RECIST CT scans after cycle 3,6,14,22 After completion of all protocol therapy, every 3 months for 2 years, then every 6 months for 3 years, then annually Perfusion CT (T2) After one week into cycle 2 Cycle 2 Perfusion CT intermediate (T1) at end of 1 st cycle between days Reproducibility Perfusion CT A subgroup of patients will be studied Paclitaxel 175 mg/m 2 IV Day 1 every cycle x 6 cycles Cycle 3 Cycle 4 Cycle 5 Cycle 6 Cycle 2 Cycle 3 Cycle 4 Cycle 5 Cycle 6 Bevacizumab 15 mg/kg IV day 1 every cycle starting cycle 2 and continuing beyond cycle 6 until progression or adverse effects preclude further treatment

ACRIN Gynecologic Committee  Scout to define limits of localization scan  Localization scan  Use site abdominal scan protocol  Define limits of tumor, either 4 or 8 cm slab  If follow-up study, try locate the same tumor slices as the initial baseline study  CT Perfusion scan as per protocol  GE Healthcare scanner - non axial shuttle mode  GE Healthcare scanner – axial shuttle mode  Toshiba Aquilion One scanner  No breath-hold, patient is instructed to breath normally during scan  Contrast dose  0.7 ml per kg body weight up to a max of 65 ml  Injection rate 3-4 ml per second  Radiation dose  4 cm coverage : 9.5 mSv  8 cm coverage : 16.8 mSV CT Perfusion Study Protocol

ACRIN Gynecologic Committee  64-slice CT scanner with 40 mm wide detector array without toggling table mode CT Perfusion Scan Protocol Inject 300 – 370 mgI/ml contrast – 4 ml/s 40 axial s intervals: 120 kVp; 100 mA; 8 x 5 mm slices; 0.4 s rotation period 0s s Effective Dose = 7.2 mSv Skin dose = 150 mGy

ACRIN Gynecologic Committee  64-slice CT scanner with 40 mm wide detector array with toggling table mode CT Perfusion Scan Protocol Inject 300 – 370 mgI/ml contrast – 4 ml/s s intervals: 120 kVp; 100 mA; 16 x 5 mm slices; 0.4 s rotation period 0s s Effective Dose = 14.3 mSv Skin dose = 150 mGy

ACRIN Gynecologic Committee  128-slice CT scanner with 80 mm wide detector array CT Perfusion Scan Protocol Inject 300 – 370 mgI/ml contrast – 4 ml/s 40 axial s intervals: 120 kVp; 100 mA; 16 x 5 mm slices; 0.4 s rotation period 0s s Effective Dose = 14.3 mSv Skin dose = 150 mGy

ACRIN Gynecologic Committee  256-slice CT scanner with 120 mm wide detector array CT Perfusion Scan Protocol Inject 300 – 370 mgI/ml contrast – 4 ml/s 40 axial s intervals: 120 kVp; 100 mA; 20 x 5 mm slices; 0.4 s rotation period 0s s Effective Dose = 17.8 mSv Skin dose = 150 mGy

ACRIN Gynecologic Committee  320-slice CT scanner with 160 mm wide detector array CT Perfusion Scan Protocol Inject 300 – 370 mgI/ml contrast – 4 ml/s 40 axial s intervals: 120 kVp; 100 mA; 24 x 5 mm slices; 0.4 s rotation period 0s s Effective Dose = 21.4 mSv Skin dose = 150 mGy

ACRIN Gynecologic Committee Example CT Perfusion Scan of Prostate Intravenous Injection of Contrast Agent ml/s Scan Protocol Each scan: 16 x 5 mm 80 kVp and 50 mAs 1 scan every 2.8 s 42 scans Deconvolution with physiol model Effective dose 21 mSv Average Blood Volume Blood Flow PS AVG BF BV PS

ACRIN Gynecologic Committee  To determine whether larger changes in the tumor perfusion parameters (BF, BV, MTT, PS) from baseline T0 to T2 are predictive of higher progression-free survival (PFS) rate at 6 months in patients treated with weekly paclitaxel regimen or every-3-week paclitaxel regimen, who are receiving carboplatin with or without bevacizumab Primary Objective

ACRIN Gynecologic Committee  To determine whether larger changes in tumor perfusion parameters from baseline T0 to T1 are predictive of higher progression-free survival (PFS) rate at 6 months in patients treated with weekly paclitaxel regimen or every- 3-week paclitaxel regimen, who are receiving carboplatin with or without bevacizumab  To determine whether larger changes in tumor perfusion parameters values from T0 to T1, T0 to T2 and T1 to T2 are predictive of better overall survival in all treatment arms.  To assess the association between changes in tumor perfusion parameters before and after chemotherapy and subsequent best tumor response according to standard anatomic response evaluation criteria (RECIST).  To assess the association between tumor perfusion parameters before chemotherapy and subsequent best tumor response according to standard anatomic response evaluation criteria (RECIST), progression free survival at 6 months and overall survival.  To test the assumption that tumor perfusion parameters are reliable, user- independent and reproducible parameters of tumor microvascular characteristics. A subgroup of 15 patients will have repeat CT Perfusion studies at T1 to achieve this objective Secondary Objectives

ACRIN Gynecologic Committee  Radiation Dose  Effective dose Research plus normal care – 87.2 mSv Annual background – 3.0 mSv  Cancer induction and fatality risk  BEIR VII report Committee to Assess Health Risks from Exposure to Low Levels of Ionizing Radiation, National Research Council Radiation Risk Excess cases of cancer (all solid cancers and leukemia including non-fatal cases) from ONE DCE-CT study per 100,000 exposed 1,195 Number of cancer cases per 100,000 in the general population not exposed to radiation 37,490 Excess cases of cancer death from ONE CT Perfusion study per 100,000 exposed 576 Number of cancer deaths per 100,000 in the general population not exposed to radiation 18,030

ACRIN Abdominal Committee ACRIN Gynecologic Committee Questions ?