The Role of Clinical Studies
for Pets with Naturally
Occurring Tumors in
TRANSLATIONAL
CANCER
RESEARCH
Workshop Summary
Sharyl J. Nass and Heather Gorby, Rapporteurs
National Cancer Policy Forum
Board on Health Care Services
Institute of Medicine
THE NATIONAL ACADEMIES PRESS
Washington, DC
www.nap.edu
THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001
This project was supported by the Animal Cancer Foundation; the College of Veterinary Medicine at North Carolina State University; the Cornell University School of Veterinary Medicine; Flint Animal Cancer Center, Colorado State University; the Morris Animal Foundation; the Ohio State University School of Veterinary Medicine; Purdue University College of Veterinary Medicine and the Center for Cancer Research; the Skippy Frank Translational Medicine and Life Sciences Fund; the University of California, Davis, School of Veterinary Medicine; the University of Colorado Cancer Center; the University of Florida College of Veterinary Medicine; the University of Georgia College of Veterinary Medicine; the University of Illinois College of Veterinary Medicine; the University of Minnesota College of Veterinary Medicine; the University of Missouri College of Veterinary Medicine and the Ellis Fischel Cancer Center; the University of Pennsylvania; the University of Wisconsin–Madison Carbone Cancer Center, Institute for Clinical and Translational Research, and the School of Veterinary Medicine; and the Washington State University College of Veterinary Medicine. Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.
International Standard Book Number-13: 978-0-309-37990-8
International Standard Book Number-10: 0-309-37990-3
DOI: 10.17226/21830
Additional copies of this workshop summary are available for sale from the National Academies Press, 500 Fifth Street, NW, Keck 360, Washington, DC 20001; (800) 624-6242 or (202) 334-3313; http://www.nap.edu.
Copyright 2015 by the National Academy of Sciences. All rights reserved.
Printed in the United States of America
Cover image contributed by Joe Mendoza/Colorado State University Photography. Angela’s surgery for her bone cancer was first developed by Dr. Withrow in pet dogs with the same disease. This treatment advancement continues to help dogs and people with bone cancer.
Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2015. The role of clinical studies for pets with naturally occurring tumors in translational cancer research: Workshop summary. Washington, DC: The National Academies Press.
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WORKSHOP PLANNING COMMITTEE1
MICHAEL B. KASTAN (Chair), Executive Director, Duke Cancer Institute
MARK DEWHIRST, Co-director, Radiation Oncology/Imaging Program, Duke University School of Medicine
CHAND KHANNA, Senior Investigator, Pediatric Oncology Branch, National Cancer Institute
JOHN K. LEIGHTON, Acting Director, Division of Hematology Oncology Toxicology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration
PATRICIA N. OLSON, Independent Advisor on Animal Health and Welfare
ELAINE A. OSTRANDER, Chief and Distinguished Investigator, National Human Genome Research Institute
BEVERLY A. TEICHER, Chief, Molecular Pharmacology Branch Developmental Therapeutics Program, National Cancer Institute
DANIEL B. TUMAS, Senior Director, Biology, Gilead Sciences, Inc.
Project Staff
SHARYL J. NASS, Director, National Cancer Policy Forum
PATRICK ROSS, Research Assistant
HANNAH DURING, Senior Program Assistant
________________
1 Institute of Medicine planning committees are solely responsible for organizing the workshop, identifying topics, and choosing speakers. The responsibility for the published workshop summary rests with the workshop rapporteurs and the institution.
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NATIONAL CANCER POLICY FORUM1
MICHAEL CALIGIURI (Chair), Chief Executive Officer, James Cancer Hospital and Solove Research Institute; Director, Ohio State University Comprehensive Cancer Center
PATRICIA A. GANZ (Vice Chair), Distinguished University Professor, University of California, Los Angeles (UCLA), Fielding School of Public Health, David Geffen School of Medicine at UCLA, Jonsson Comprehensive Cancer Center
AMY P. ABERNETHY, Chief Medical Officer and Senior Vice President for Oncology, Flatiron Health; Professor, Division of Medical Oncology, Duke University School of Medicine; Director, Center for Learning Health Care, Duke Clinical Research Institute
LUCILE ADAMS-CAMPBELL, Professor of Oncology, Associate Director for Minority Health and Health Disparities Research, Georgetown University Lombardi Cancer Center
KENNETH ANDERSON, Kraft Family Professor of Medicine, American Cancer Society Clinical Research Director, Jerome Lipper Multiple Myeloma Center, Harvard Medical School, Dana-Farber Cancer Institute
LOYCE PACE BASS, Health Policy Director, LIVESTRONG Foundation
MONICA BERTAGNOLLI, Professor of Surgery, Harvard Medical School
OTIS BRAWLEY, Chief Medical Officer and Executive Vice President, American Cancer Society
CARLTON BROWN, Director of Professional Services, Oregon Nurses Association; Past President, Oncology Nursing Society
SERGIO CANTOREGGI, Chief Scientific Officer and Global Head of Research and Development, Helsinn Group
ROBERT W. CARLSON, Chief Executive Officer, National Comprehensive Cancer Network
GREGORY CURT, U.S. Medical Science Lead, AstraZeneca
________________
1 Institute of Medicine planning committees are solely responsible for organizing the workshop, identifying topics, and choosing speakers. The responsibility for the published workshop summary rests with the workshop rapporteurs and the institution.
WILLIAM S. DALTON, Chief Executive Officer, M2Gen Personalized Medicine Institute, Moffitt Cancer Center; Chair, American Association for Cancer Research Science Policy and Government Affairs Committee
GWEN DARIEN, Executive Vice President, Programs and Services, Cancer Policy Institute, Cancer Support Community
WENDY DEMARK-WAHNEFRIED, Associate Director for Cancer Prevention and Control, University of Alabama at Birmingham Comprehensive Cancer Center
JAMES DOROSHOW, Deputy Director, National Cancer Institute
CAROL A. HAHN, Associate Professor of Radiation Oncology, Duke University Medical Center; Medical Director of Radiation Oncology, Duke Raleigh Hospital; Clinical Affairs and Quality Council Chair, American Society for Radiation Oncology
LORI HOFFMAN HŌGG, Veterans Health Administration National Oncology Clinical Advisor, Office of Nursing Services; Cancer Program Director, Albany Stratton Veterans Affairs Medical Center
SAMIR N. KHLEIF, Director, Georgia Health Sciences University Cancer Center, Georgia Regents University Cancer Center
RONALD M. KLINE, Medical Officer, Patient Care Models Group, Center for Medicare & Medicaid Innovation
LEE M. KRUG, Disease Area Head, Immuno-Oncology, Bristol-Myers Squibb
RICHARD A. LARSON, Hematology/Oncology Director, University of Chicago
MICHELLE M. LE BEAU, Arthur and Marian Edelstein Professor of Medicine, Director, Comprehensive Cancer Center, University of Chicago
GRETA MASSETTI, Associate Director for Science, Division of Cancer Prevention and Control, Centers for Disease Control and Prevention
DANIEL R. MASYS, Affiliate Professor, Biomedical Informatics, University of Washington
MARTIN J. MURPHY, Chief Executive Officer, CEO Roundtable on Cancer
RICHARD PAZDUR, Director, Office of Oncology and Hematology Products, U.S. Food and Drug Administration
STEVEN PIANTADOSI, Phase One Foundation Endowed Chair and Director, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center
JENNIFER A. PIETENPOL, Director, Vanderbilt-Ingraham Cancer Center, Benjamin F. Byrd, Jr., Professor of Oncology, Professor of Biochemistry, Vanderbilt University
AUGUST SALVADO, Senior Vice President, U.S. Oncology Clinical Development & Medical Affairs, Novartis Oncology
ANDREW SCHIERMEIER, Senior Vice President, Head of Global Oncology, Merck Serono
RICHARD SCHILSKY, Chief Medical Officer, American Society of Clinical Oncology
DEBORAH SCHRAG, Chief, Division of Population Sciences, Professor of Medicine, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School
YA-CHEN TINA SHIH, Professor of Health Economics, Chief, Section of Cancer Economics and Policy, Department of Health Services Research, University of Texas MD Anderson Cancer Center
ELLEN V. SIGAL, Chair and Founder, Friends of Cancer Research
RALPH WEICHSELBAUM, Daniel K. Ludwig Professor and Chair, Department of Radiation Oncology, Director, Ludwig Center for Metastasis Research, The University of Chicago Medical Center
GEORGE J. WEINER, Director, Holden Comprehensive Cancer Center, University of Iowa; President, Association of American Cancer Institutes
WENDY WOODWARD, Associate Professor and the Section Chief of Clinical Breast Radiation, Department of Radiation Oncology, University of Texas MD Anderson Cancer Center
National Cancer Policy Forum Staff
SHARYL J. NASS, Forum Director and Director, Board on Health Care Services
ERIN BALOGH, Program Officer
PATRICK ROSS, Research Assistant
HANNAH DURING, Senior Program Assistant (until August 2015)
CYNDI TRANG, Senior Program Assistant (from August 2015)
PATRICK BURKE, Financial Associate
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Reviewers
This workshop summary has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published workshop summary as sound as possible and to ensure that the workshop summary meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the process. We wish to thank the following individuals for their review of this workshop summary:
JEFF ALLEN, Friends of Cancer Research
PETER CHOYKE, National Cancer Institute
SHIVAANI KUMMAR, Stanford University Medical Center
PERRY NISEN, Sanford Burnham Prebys Medical Discovery Institute
SUZANNE PARSEL, Kansas State University
Although the reviewers listed above have provided many constructive comments and suggestions, they did not see the final draft of the workshop summary before its release. The review of this report was overseen by ELI Y. ADASHI, Warren Alpert Medical School at Brown University. He was responsible for making certain that an independent examination
of this report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this report rests entirely with the rapporteurs and the institution.
Acknowledgments
We thank the coalition of sponsors who supported this project. The sponsors included the Animal Cancer Foundation; the College of Veterinary Medicine at North Carolina State University; the Cornell University School of Veterinary Medicine; Flint Animal Cancer Center, Colorado State University; the Morris Animal Foundation; the Ohio State University School of Veterinary Medicine; Purdue University College of Veterinary Medicine and the Center for Cancer Research; the Skippy Frank Translational Medicine and Life Sciences Fund; the University of California, Davis, School of Veterinary Medicine; the University of Colorado Cancer Center; the University of Florida College of Veterinary Medicine; the University of Georgia College of Veterinary Medicine; the University of Illinois College of Veterinary Medicine; the University of Minnesota College of Veterinary Medicine; the University of Missouri College of Veterinary Medicine and the Ellis Fischel Cancer Center; the University of Pennsylvania; the University of Wisconsin–Madison Carbone Cancer Center, Institute for Clinical and Translational Research, and the School of Veterinary Medicine; and the Washington State University College of Veterinary Medicine.
Support from the many annual sponsors of the Institute of Medicine’s National Cancer Policy Forum is also crucial to the work of the Forum. Federal sponsors include the Centers for Disease Control and Prevention and the National Cancer Institute/National Institutes of Health. Nonfederal sponsors include the American Association for Cancer Research, American
Cancer Society, American Society for Radiation Oncology, American Society of Clinical Oncology, American Society of Hematology, Association of American Cancer Institutes, AstraZeneca, Bristol-Myers Squibb, Cancer Support Community, CEO Roundtable on Cancer, EMD Serono, Helsinn Healthcare SA, LIVESTRONG Foundation, National Comprehensive Cancer Network, Novartis Oncology, and the Oncology Nursing Society.
The Forum wishes to express its gratitude to the expert speakers whose presentations helped define the current challenges and opportunities for integrating comparative oncology trials within the cancer research continuum. The Forum also wishes to thank the members of the planning committee for their work in developing an excellent workshop agenda.
Contents
OVERVIEW OF THE RATIONALE FOR COMPARATIVE ONCOLOGY TRIALS
Limitations of Traditional Drug Development Preclinical Research Models
Similarities Between Human Cancers and Naturally Occurring Cancers in Pet Patients
The Integrated Comparative Clinical Trial Approach
Examples of Clinical Trials for Pets with Naturally Occurring Cancers
Risks and Challenges of Clinical Trials for Pet Patients
Genomic Resources for Comparative Oncology Clinical Trials
Canine Comparative Oncology and Genomics Consortium
OPPORTUNITIES FOR INTEGRATING BIOMARKERS INTO STUDY DESIGNS
Pharmacokinetics in Clinical Trials for Pet Patients
Pharmacodynamics in Clinical Trials for Pet Patients
IMAGING TECHNOLOGY IN CLINICAL TRIALS FOR PET PATIENTS
Challenges and Opportunities in Using PET Imaging in Clinical Trials
Challenges and Opportunities in Using MRI Imaging in Clinical Trials
LESSONS LEARNED FROM COMPARATIVE ONCOLOGY CLINICAL TRIALS
Single-Institution Clinical Trials
Multi-Institution Clinical Trials
Clinical Trial Designs That Meet the Needs of Pet Patients and Their Owners
Best Practices for the Ethical Conduct of Clinical Trials for Pet Patients
Considerations of Pet Owners and Pet Patients in the Conduct of Clinical Trials
REGULATORY OVERSIGHT AND REPORTING REQUIREMENTS IN CLINICAL TRIALS FOR PET PATIENTS
STATUS OF CLINICAL TRIALS FOR PET PATIENTS
Box, Figures, and Tables
BOX
1 Suggestions Made by Individual Workshop Participants
FIGURES
1 A comparative and integrated approach to cancer drug development
2 Projected value of an integrated drug development path
3 Clinical trial approval process at the Cornell University College of Veterinary Medicine
4 Clinical development success rates for investigational drugs
TABLES
1 Mouse Models in Cancer Research
2 Examples of Clinical Trials for Pet Patients That Informed the Design of Trials for Human Patients
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ATP | adenosine triphosphate |
BTK | Bruton tyrosine kinase |
CCOGC | Canine Comparative Oncology and Genomics Consortium |
CML | chronic myeloid leukemia |
COTC | Comparative Oncology Trials Consortium |
CT | computed tomography |
CTVT | canine transmissible venereal tumor |
DCE-MRI | dynamic contrast-enhanced magnetic resonance imaging |
DSMB | data safety and monitoring board |
FDA | U.S. Food and Drug Administration |
FDG | flourodeoxyglucose |
FLT | fluorothymidine |
F-TFB | F-tetrafluoroborate |
GEMM | Genomic-Enabled Medicine for Melanoma (trial) |
HCQ | hydroxychloroquine |
HIPAA | Health Insurance Portability and Accountability Act |
IACUC | institutional animal care and use committee |
IND | investigational new drug (application) |
IOM | Institute of Medicine |
IRB | institutional review board |
MRI | magnetic resonance imaging |
MTD | maximum tolerated dose |
NCI | National Cancer Institute |
NHL | non-Hodgkin’s lymphoma |
PBMC | peripheral blood mononuclear cell |
PD | pharmacodynamic |
PDX | patient-derived xenograft |
PET | positron emission tomography |
PI | principal investigator |
PK | pharmacokinetic |
TBR | target-to-background ratio |
TCC | transitional cell carcinoma |
TGEN | Translational Genomics Research Institute |
TNF | tumor necrosis factor |