Proposal for facilitating protocol development and site pre-activation

1. ACRIN Accelerated Accrual Demonstration Project: Univ. of Southern California and MD Anderson Collaboration Proposal for facilitating protocol development and site pre-activation Suzanne L. Palmer, M.D. Tammie Possemato Chaan Ng, M.D. SujayaRao Michelle Haynes

2. #2 Site pre-activation phase #1 Protocol development phase

3. #1 Protocol development phase • Brief Study Summary • Schema • Study objectives and end points • Patient eligibility and enrollment • Associated therapy or tissue biomarker studies • Imaging and equipment requirements • Minimum imaging requirements • Timeline for required imaging • Information needed for the sites to evaluate recruitment potential • Clinical services involved • Study schedule • Reimbursement

4. #2 Site pre-activation phase • Individual site assessment • Performed by RA and/or PI • Step-by-step • Review of the brief study summary • Assess study requirements and match to site’s resources • Estimate patient recruitments • The Mock Screen • Identify radiology department personnel and conferences • Identify referring clinicians and coordinators • Identify tumor boards and other sources of patient recruitment • If the site assessment is successful, the activation and recruitment phases should go more rapidly.

5. #2 Site pre-activation phase • Individual site assessment • Performed by RA and/or PI • Step-by-step • Review of the brief study summary • Assess study requirements and match to site’s resources • Estimate patient recruitments • The Mock Screen • Identify radiology department personnel and conferences • Identify referring clinicians and coordinators • Identify tumor boards and other sources of patient recruitment • If the site assessment is successful, the activation and recruitment phases should go more rapidly.

6. #2 Site pre-activation phase • Individual site assessment • Performed by RA and/or PI • Step-by-step • Review of the brief study summary • Assess study requirements and match to site’s resources • Estimate patient recruitments • The Mock Screen • Identify radiology department personnel and conferences • Identify referring clinicians and coordinators • Identify tumor boards and other sources of patient recruitment • If the site assessment is successful, the activation and recruitment phases should go more rapidly.

7. #2 Site pre-activation phase • Individual site assessment • Performed by RA and/or PI • Step-by-step • Review of the brief study summary • Assess study requirements and match to site’s resources • Estimate patient recruitments • The Mock Screen • Identify radiology department personnel and conferences • Identify referring clinicians and coordinators • Identify tumor boards and other sources of patient recruitment • If the site assessment is successful, the activation and recruitment phases should go more rapidly.

8. #2 Site pre-activation phase • Individual site assessment • Performed by RA and/or PI • Step-by-step • Review of the brief study summary • Assess study requirements and match to site’s resources • Estimate patient recruitments • The Mock Screen • Identify radiology department personnel and conferences • Identify referring clinicians and coordinators • Identify tumor boards and other sources of patient recruitment • If the site assessment is successful, the activation and recruitment phases should go more rapidly.

9. Data extraction capability: Examples of sample tables: Important information for the ACRIN Study Group Protocol #:  6695                                         ACRIN PI: Chaan Ng                      ACRIN project manager: Bernadine Dunning

10. Data extraction capability: Different forms/format examples: Important information for the Study Site ACRIN 6690 SITE PERSONNEL OVERVIEW RADIOLOGY: P.I. Suzanne Palmer Email/Phone #: spalmer@usc.edu 323-442-8541 Responsibilities: PI responsible for all aspects of the study. RA Tammie Possemato Email/Phone #: tpossemat@usc.edu 323-442-7263 Responsibilities: Assists PI with all aspects of study. CLINICAL SERVICES: Abdominal Transplant John Donovan Email Address: jdonovan@usc.edu Responsibilities: Access to UNOS database, ordering of UNOS recertification CT 90 days. UNOS Contact: Jennifer Pena Email Address: jpena@usc.edu Responsibilities: Notification of MELD Listing Pathology Lydia Petrovich Email Address: lpertrov@usc.edu Responsibilities: Comparison of imaging to explant. Oncology: Anthony ElKhoureiy Email Address: aelkhou@usc.edu Responsibilities: Patient referral Surgery: Yuri Genyk Email Address: ygenyk@usc.edu Responsibilities: Patient referral PATIENT IDENTIFICATION/RECRUITMENT SOURCES: Protocol#:  6690                                       ACRIN PI: Christoph Wald                     ACRIN project manager: Donna Hartfeil

11. Data extraction capability: Different forms/format examples: Important information for the Study Site STUDY SUMMARY ACRIN Study #: 6690 ACRIN Study Name: Comparison of multiphase contrast-enhanced CT and MRI for diagnosis of HCC and liver transplant allocation Study Contact Information : ACRIN PI: Christoph Wald, MD, Ph.D, 781-744-8170 christoph.wald@lahey ACRIN Project Manager: Donna Hartfeil, 215 717-2765, dhartfeil@acr.org Site Number: 4317 Site PI: Suzanne Palmer, M.D., 323.442.8721, spalmer@usc.edu Site RA: Tammie Possemato, 323.442. 7263, tpossemat@usc.edu ACRIN Schema: Study objectives and end points: The main objective of the ACRIN 6690 trial is to compare modern multiphase contrast-enhanced CT and MRI with pathologic liver findings to establish the performance characteristics of these imaging modalities to accurately detect, diagnose, and stage HCC in patients with chronic liver disease. The CT and MRI examinations acquired within 90 days of transplantation will be compared with the explant pathology findings.   The primary analysis will compare CT to MRI results at the lesion level using core laboratory interpretations of the imaging studies; secondary analysis will be performed at the patient level. Patient eligibility: Patients diagnosed with HCC and listed for liver transplant surgery with priority MELD (Model for End-Stage Liver Disease) points based on their cancer diagnosis will participate. Eligible patients include those who may be waiting for a liver to become available from a deceased donor or be scheduled to undergo a living donor adult liver transplant. Patients must enroll in the trial within 30 days after initial listing with HCC-exception points to the United Network for Organ Sharing (UNOS) waitlist. Basic protocol: Each site will image a participant with CT or MRI approximately every 90 days (or earlier) per the OPTN/UNOS HCC-exception point update requirements for their region. This imaging to evaluate disease is considered standard of care. This research trial requires that complement imaging (CT or MRI, whichever imaging was not done as the standard of care) be completed at each 90-day interval. This imaging must be completed within 7 days of the standard-of-care imaging for that time interval. The goal is to compare the CT and MRI examinations acquired within 90 days of transplantation with explant pathology findings. Should a participant undergo local ablative therapy, CT and MRI should be completed no less than 28 days and no more than 60 days after each completed ablative therapy scheme. Enrollment: A total of 440 participants will be accrued to the ACRIN 6690 trial. Number per site was not included in available protocol

12. Significant outcomes, to date:USC results using our tool

13. And finally………. Congratulations to Tammie Possemato for being honored as the recipient of the Jo-Ann D’Amato Award!