Principles of Oncology: Recent AdvancesPhase 0 Clinical Trials: Conceptions and MisconceptionsKummar, Shivaani MD*; Rubinstein, Larry PhD†; Kinders, Robert PhD‡; Parchment, Ralph E. PhD‡; Gutierrez, Martin E. MD*; Murgo, Anthony J. MD, MS, FACP†; Ji, Jay PhD‡; Mroczkowski, Barbara PhD†; Pickeral, Oxana K. MBA, PhD†; Simpson, Mel PhD‡; Hollingshead, Melinda DVM, PhD†; Yang, Sherry X. MD, PhD†; Helman, Lee MD*; Wiltrout, Robert PhD*; Collins, Jerry PhD†; Tomaszewski, Joseph E. PhD†; Doroshow, James H. MD*†Author Information From the *Center for Cancer Research, †Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, Maryland 20892; and ‡Laboratory of Human Toxicology and Pharmacology, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland 21702. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. Reprint requests: James H. Doroshow, MD, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bldg. 31, Room 3A44, 31 Center Drive, NIH, Bethesda, MD 20892. E-mail: [email protected]. The Cancer Journal: May 2008 - Volume 14 - Issue 3 - p 133-137 doi: 10.1097/PPO.0b013e318172d6f3 Buy Metrics Abstract Phase 0 clinical trials, developed in response to the United States Food and Drug Administration (FDA)'s recent exploratory Investigational New Drug (IND) guidance, are intended to expedite the clinical evaluation of new molecular entities. The exploratory IND supports the performance of first-in-human testing of new investigational agents at subtherapeutic doses based on reduced manufacturing and toxicologic requirements, allowing the demonstration of drug-target effects and assessment of pharmacokinetic–pharmacodynamic relationships in humans earlier in clinical development. The objectives of a phase 0 cancer clinical trial are to establish at the very earliest opportunity—before large numbers of patients have been accrued and exposed to potential drug-associated toxicity—whether an agent is modulating its target in a tumor, and consequently whether further clinical development is warranted. We review here the fundamental requirements of clinical studies conducted under an exploratory IND and address some common misconceptions regarding oncologic phase 0 trials. © 2008 Lippincott Williams & Wilkins, Inc.