title: Phase 0 clinical trials in cancer drug development: from FDA guidance to clinical practice.
abstract: The Food and Drug Administration (FDA) recently introduced the Exploratory Investigational New Drug Guidance to expedite the clinical evaluation of new therapeutic and imaging agents. Early clinical studies performed under the auspices of this guidance, so-called "Phase 0" trials, have been initiated at the National Cancer Institute to integrate qualified pharmacodynamic biomarker assays into first-in-human cancer clinical trials of molecularly targeted agents. The goal of this integration is to perform molecular proof-of-concept investigations at the earliest stage of cancer drug development. Phase 0 trials do not offer any possibility of patient benefit; instead, intensive, real-time pharmacodynamic and pharmacokinetic analyses of patient tumor samples and/or surrogate tissues are performed to inform subsequent trials. Phase 0 studies do not replace formal Phase I drug safety testing and require a substantial investment of resources in assay development early on; however, they offer the promise of more rational selection of agents for further, large-scale development as well as the molecular identification of potential therapeutic failures early in the development process.
authors.affiliation: Laboratory of Human Toxicology and Pharmacology, Applied/Developmental Research Support Directorate, SAIC-Frederick Inc., NCI-Frederick, Frederick, Maryland 21702, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Kinders
authors.forename: Ralph E
authors.initials: RE
authors.lastname: Parchment
authors.forename: Jay
authors.initials: J
authors.lastname: Ji
authors.forename: Shivaani
authors.initials: S
authors.lastname: Kummar
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Murgo
authors.forename: Martin
authors.initials: M
authors.lastname: Gutierrez
authors.forename: Jerry
authors.initials: J
authors.lastname: Collins
authors.forename: Larry
authors.initials: L
authors.lastname: Rubinstein
authors.forename: Oxana
authors.initials: O
authors.lastname: Pickeral
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: Sherry
authors.initials: S
authors.lastname: Yang
authors.forename: Melinda
authors.initials: M
authors.lastname: Hollingshead
authors.forename: Alice
authors.initials: A
authors.lastname: Chen
authors.forename: Lee
authors.initials: L
authors.lastname: Helman
authors.forename: Robert
authors.initials: R
authors.lastname: Wiltrout
authors.forename: Mel
authors.initials: M
authors.lastname: Simpson
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Tomaszewski
authors.forename: James H
authors.initials: JH
authors.lastname: Doroshow
mesh_terms: D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D002986:Clinical Trials as Topic / Q000941:ethics / Q000379:methods*; D015195:Drug Design; D015507:Drugs, Investigational / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000970:Antineoplastic Agents; D015507:Drugs, Investigational