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Oncologic Phase 0 Trials Incorporating Clinical Pharmacodynamics: from Concept to Patient

Authors' Affiliations: ¹ Division of Cancer Treatment and Diagnosis, and the Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland; and ² Laboratory of Human Toxicology and Pharmacology, Applied/Developmental Research Support Directorate, Science Applications International Corporation-Frederick, Inc., National Cancer Institute-Frederick, Frederick, Maryland

Requests for reprints: James H. Doroshow, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Building 31, Room 3A-44, 31 Center Drive, NIH, Bethesda, MD 20892. Phone: 301-496-4291; Fax: 301-496-0826; E-mail: doroshoj{at}mail.nih.gov.

Abstract

The U.S. Food and Drug Administration recently issued an Exploratory Investigational New Drug (IND) guidance that provides a platform for the evaluation of targeted anticancer agents in small, early-phase human clinical trials that can be used to establish the feasibility of proof-of-principle target modulation assays, as well as the preliminary pharmacokinetics and molecular imaging potential of new anticancer molecules. The exploratory IND allows for reduced requirements for manufacturing and toxicologic assessment. Early clinical trials done in this fashion have no therapeutic intent. In this series of articles in CCR Focus, the development of this new IND mechanism, its effect on clinical trial design and clinical pharmacodynamics, the ethical implications of nontherapeutic clinical investigations, and the perspective of the pharmaceutical industry on this approach are examined.

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