2011 ACRIN Annual Meeting Proposal for facilitating protocol development and site pre-activation Suzanne L. Palmer, M.D. Tammie Possemato Chaan Ng, M.D. Sujaya Rao Michelle Haynes ACRIN Accelerated Accrual Demonstration Project: Univ. of Southern California and MD Anderson Collaboration

2011 ACRIN Annual Meeting #1 Protocol development phase #2 Site pre-activation phase

2011 ACRIN Annual Meeting #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

2011 ACRIN Annual Meeting #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.

2011 ACRIN Annual Meeting #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.

2011 ACRIN Annual Meeting #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.

2011 ACRIN Annual Meeting #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.

2011 ACRIN Annual Meeting #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.

2011 ACRIN Annual Meeting Data extraction capability: Examples of sample tables: Important information for the ACRIN Study Group Site numberPI name/contactRA name/contactTarget pop available Inc/excl feasible Interest in participating Why no? 4206Jeffrey Brody Wendy Smith yes noDon’t have the time 4567Ronald McDonald Hamburglar no yes 4317Suzanne Palmer Tammie Possemato yesno Site not participating in GOG 0262 Protocol #: 6695 ACRIN PI: Chaan Ng ACRIN project manager: Bernadine Dunning Site numberEstimated # of patients 42062/ month 45670/month 43171/month

2011 ACRIN Annual Meeting Protocol#: 6690 ACRIN PI: Christoph Wald ACRIN project manager: Donna Hartfeil Data extraction capability: Different forms/format examples: Important information for the Study Site SourceTime/LocationContactClinical Services Attending Liver tumor boardTuesday/wk/ 2pm - UHJennifer Pena UNOS Websitehttps://portal.unos.orgPassword ACRIN 6690 SITE PERSONNEL OVERVIEW RADIOLOGY: P.I. Suzanne Palmer /Phone #: Responsibilities: PI responsible for all aspects of the RA Tammie Possemato /Phone #: Responsibilities: Assists PI with all aspects of study. CLINICAL SERVICES: Abdominal Transplant John Donovan Address: Responsibilities: Access to UNOS database, ordering of UNOS recertification CT 90 days. UNOS Contact: Jennifer Pena Address: Responsibilities: Notification of MELD Listing Pathology Lydia Petrovich Address: Responsibilities: Comparison of imaging to explant. Oncology: Anthony ElKhoureiy Address: Responsibilities: Patient referral Surgery: Yuri Genyk Address: Responsibilities: Patient referral PATIENT IDENTIFICATION/RECRUITMENT SOURCES:

2011 ACRIN Annual Meeting 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, ACRIN Project Manager: Donna Hartfeil, , Site Number: 4317 Site PI: Suzanne Palmer, M.D., , Site RA: Tammie Possemato, , 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

2011 ACRIN Annual Meeting Significant outcomes, to date: USC results using our tool USC Study Accrual (as of 9/15) Problems Identified through Mock Screen Solutions/Outcomes Difficulty identifying potential patients; multiple competing studies; oncology in charge of study assignment and interested in accruing to competing studies Change in PI. Tumor boards identified and attended; contact made with referring MD’s; potential patients identified at conferences Difficulty identifying potential patients; disinterested PI; no communication with clinical services; requirements for imaging not reviewed for access to radiotracer and equipment needs Added PI with interest in gynecologic imaging; regular attendance at weekly tumor boards; imaging road blocks identified and resolved Difficulty identifying patients for study; potential patients not interested in participating due to QOL questionnaire; inclusion criteria for N0 neck not well defined; reimbursement inadequate Working with clinical MD’s to recruit patients from clinic and tumor boards; working with ACRIN for clarification of eligibility; attempt to convince USC to drop tithing for this study Difficulty identifying patients for study; multiple competing studies; failure of RA to follow-up on patients identified in tumor boards. Replaced recruiting RA Timing for patient recruitment critical. Knowledge of MELD exception application and any scheduled or completed treatment. RA at weekly conference where patients are listed for MELD exception, and recruited to study with clinical support. One of the first 10 sites to open.

2011 ACRIN Annual Meeting And finally………. Congratulations to Tammie Possemato for being honored as the recipient of the Jo-Ann D’Amato Award!