The seamless trials included a median of 3 (range = 1-13) expansion cohorts. Fifty-one of the trials (2.9%) investigated 50 investigational new drugs, were seamless, and accounted for 14.6% of the total patients. We identified 1786 early-phase trials enrolling 57 559 adult patients. We reviewed all abstracts presented at American Society of Clinical Oncology annual meetings from 2010 to 2017 for FiH trials enrolling at least 100 patients. A working group formed by the National Cancer Institute convened to consider and discuss opportunities and challenges for such trials as well as encourage responsible use of these designs.
Seamless designs trial#
Although consolidation and rapid accrual may yield efficiencies, widespread use of seamless first-in-human (FiH) trials without careful consideration of objectives, statistical analysis plans, or trial oversight raises concerns. Innovations in drug development seek to consolidate the phases and rapidly expand accrual with "seamless" trial designs. Traditionally, drug development has evaluated dose, safety, activity, and comparative benefit in a sequence of phases using trial designs and endpoints specifically devised for each phase. 21 Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins, Baltimore, MD.20 National Cancer Institute, Coordinating Center for Clinical Trials, Rockville, MD.19 National Cancer Institute, Cancer Therapy Evaluation Program, Rockville, MD.17 Cancer Immunotherapy- Global Product Development Oncology, Genentech, Inc., San Francisco, CA.16 Center for Research and Analytics, American Society of Clinical Oncology, Alexandria, VA.15 Early Clinical Development, Bristol-Myers Squibb, Princeton, NJ.14 Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX.13 Division of Translational Research & Applied Statistics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA.12 Canadian Cancer Trials Group, Queen's University, Kingston, ON, Canada.11 Global Clinical Oncology, Merck Research Laboratories, Kenilworth, NJ.10 Breast Cancer Program, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD.9 Office of Hematology & Oncology Products, Food and Drug Administration, Silver Spring, MD.8 Department of Oncology, McMaster University, Hamilton, ON, Canada.6 Department of Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD.
5 Department of Medical Oncology, Prince of Wales Hospital, Sydney, Australia.4 Division of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.3 Department of Internal Medicine, Division of Hematology and Medical Oncology, Tulane University Medical School, New Orleans, LA.2 Division of Hematology and Medical Oncology, Taussig Cancer Institute Cleveland Clinic, Cleveland, OH.1 Quantitative Health Sciences and Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH.
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