Oncology Clinical Trials Sylvia O’Neill, MD Executive Director Clinical Research Organization Teresa Cardoso, MS,BSN,RN Clinical Trial Nurse Educator

Sidney Kimmel Cancer Center (SKCC) US News and World Report ranked No.20 in the nation for 2017-2018 Increased ranking from 2016-2017 No.29

Sidney Kimmel Cancer Center (SKCC) Founded in 1991 1995 became a NCI -Designated Center One of 69 NCI-designated institutions in United States

What is NCI Designation? NCI-Designated Cancer Centers are recognized for their scientific leadership, in basic, clinical, and/or population science A large NCI grant (also referred to as the P30-Cancer Center Support Grant or CCSG) is submitted and then awarded to institutions who demonstrate the most impact through research CCSGs currently range from $1.4M-8M/yr Size of the center How long the center has had the CCSG in place Overall impact in the field of oncology as judged by peer scientists

NCI-Designation Review Process Grant is renewed every five years One day site visit scheduled October 24, 2017 20 nationally recognized cancer scientists from other NCI-designated centers Evaluating the Center’s research portfolio, leadership, and infrastructure SKCC CCSG next anticipated renewal 2021 NCI Parent Committee Renewal and Funding Site Report NCI Advisory Board

What are the NCI Expectations? Clinical Protocol & Data Management (CRO & DSMC) Protocol Review & Monitoring System (PRC) Senior Leadership Administration Planning and Evaluation Developmental Funds Addressing the Catchment Area Professional Education & Career Development Research Programs Shared Resources Minority & Women in Clinical Research

Clinical Protocol and Data Management (CPDM)

Karen Knudsen, PhD SKCC Director William Kevin Kelly, DO Associate Director of Clinical Research Sylvia O’Neill, MD Executive Director Clinical Research Organization 215-275-3045 Early Drug Development Office Sr. Director Barbara Osborne,RN,MPH,MBA 267-640-6519 Clinical Trials Office Sr. Director, Meghan Wakefield, RN,CCRP 267-315-3562 Regional Network Office Sr. Director, Joshua Schoppe, MPH,CCRP 267-872-7414 Protocol Support Unit Director, Sarah deVries, MSEd, CCRP 814-404-6443 Quality Assurance and Process Improvement Unit Director, Christine Jerome, BS, CCRP 215-498-3399

Clinical Nurse Educator PRMS and DSMC Coordinator K. Knudsen, PhD SKCC Director M. Huesser, MBA AD Admin & Ops W.K. Kelly, DO AD Clinical Research Adam Berger,MD PRC Chair S. O’Neill, MD CRO Exec. Director J. Hoffman-Censits, MD DSMC Chair Clinical Nurse Educator T. Cardoso* OnCore (JeffTrials) IT Administrator N. Van Kuren Clinical Trials Office (CTO) M. Wakefield Senior Director Early Drug Development Office (EDDO) B. Osborne Senior Director Reginal Network Office J. Schoppe Senior Director Protocol Support Unit (PSU) S. deVries Director Quality Assurance & Process Improvement Unit (QIU) C. Jerome Director PRMS and DSMC Coordinator A. Madineni

Multidisciplinary Disease Group (MDGs) Solid tumor Breast GI GU Aerodigestive Heme Melanoma Phase I Brain, CNS, GYN-Cervix, Endometrial, Pelvic, Ovarian, Uterine Breast Colon, Gastric, Gastro-esophageal, Hepatocellular, Pancreatic, Rectal Bladder, Prostate, Renal Head, Laryngeal, Lips, Lung, Nasal, Oral Cavity, Pharyngeal, Thoracic BMT, Leukemia, Lymphoma, MDS, Myeloma Melanoma, Uveal Melanoma All Solid Tumor Types

Data and Safety Monitoring Committee (DSMC) JEAN HOFFMAN-CENSITS, MD Data and Safety Monitoring Chair NCI requirement and subsection of CPDM component Administratively supported by the QA and Process Improvement Unit (QIU) of the CRO Reports to Dr. Kelly, AD Clinical Research

Data and Safety Monitoring Committee (DSMC) Reviews all IIT interventional trials regardless of phases and is part of the DSMP that is approved by the NCI Meets quarterly or ad hoc Mandatory dose escalation/cohort expansion meetings IRB notified at continuing review since delineated in the protocol Assigns medical monitors before a trial is activated Review SAEs in real time Recommends continuation, suspension, or termination IRB notified in real time if deemed major by the DSMC and at CR if minor

Interventional vs. Non-Interventional Studies *Participants are assigned to receive one or more interventions (or no intervention) *Evaluate effects of interventions on biomedical or health-related outcomes Examples: Diagnostic studies Screening studies Treatment studies Non-Interventional *Prospective or retrospective studies collecting data and not interfering with the choice of treatment, sample collection, procedures and the treatment itself. Observational studies Epidemiology studies

DSM Plan AE/SAE Reporting Guidelines*   Grade 1 Grade 2 Grade 3 Grades 4 and 5 Unexpected and Expected Unexpected Expected With Hospitalization Without Hospitalization Unrelated Unlikely Reviewed at Quarterly DSMC Meeting and IRB Annual Review 5 Working Days Phase 1 - 48 Hours (Death: 24 Hours) Phase 2 - Possible Probable Definite 48 Hour 5 Working Days 48 Hours (Death: 24 Hours) Phase 1 and Phase 2 - NOTE: This table is based on the NCI AE/SAE reporting Guidelines and the TJU IRB Policy and Procedures. Please follow the individual protocol AE/SAE reporting guidelines if more stringent reporting procedures are specified. *From the KCC DMS Plan version 2.10, page 18

Adverse Event Grading in Oncology Clinical Trials

Protocol Review and Monitoring System (PRMS)

Protocol Review Committee (PRC) Responsibilities Reviews all clinical trials for scientific merit, prioritization, progress, feasibility Not to duplicate IRB efforts Reviews trials at least annually Closes trials : Lack of scientific progress lack accrual within 6 months ADAM BERGER, MD, FACS Protocol Review Committee Chair

Protocol Review Committee (PRC) All new studies, including retrospective chart reviews, must be submitted to PRC and get approved before they can go to IRB Some protocol amendments must be submitted to PRC for approval PRC does not review informed consent PRC meets twice a month

New Protocol Submission Process MDG Facilitation Committee Amendments and CRs New trial PRC and IRB Simultaneous PRC 90 Days IRB Activation

Overview of the NCI Central (CIRB) Model MISSION: National efficient review of oncology clinical trials funded by the NCI Helping the NCI accelerate scientific discovery and improve cancer prevention, treatment and care. Protection of the rights and welfare of participants in cancer clinical trials. Ethical and quality standards.

NCI CIRB History Previous model of facilitated review was parallel process Current model As of January 1, 2014 CIRB operates as “independent model” CIRB is IRB of Record Required for NCTN studies SOP for TJU IRB and CRO OHR-8K

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