Toggle Main Menu Toggle Search

Open Access padlockePrints

The Development of Phase I Cancer Trial Methodologies: the Use of Pharmacokinetic and Pharmacodynamic End Points Sets the Scene for Phase 0 Cancer Clinical Trials

Lookup NU author(s): Professor Alan Calvert, Professor Ruth Plummer


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Although the concept of a phase 0 trial is a relatively new one, there has been a slowly increasing trend toward basing early clinical trial designs on pharmacokinetic and pharmacodynamic end points that has been developing over many years. This article will review the early cancer trial methodologies and the various techniques that have been used to refine them. Several illustrative examples will be presented showing their relevance to trial designs using pharmacodynamic end points and targeted agents. Some criteria for characterizing suitable phase 0 end points are suggested. Four trial designs that are essentially developed for cytotoxic agents using the maximal tolerated dose as an end point are described. Although these trials were not designed with the use of more sophisticated pharmacodynamic end points (such as the measurement of the effect of a targeted agent on its target), they have been developed to optimize the speed with which a dose needed to achieve a particular effect can be determined and are, to this extent, relevant to the design of studies with pharmacodynamic end points.

Publication metadata

Author(s): Calvert AH, Plummer ER

Publication type: Article

Publication status: Published

Journal: Clinical Cancer Research

Year: 2008

Volume: 14

Issue: 12

Pages: 3664-3669

ISSN (print): 1078-0432

ISSN (electronic): 1557-3265

Publisher: American Association for Cancer Research


DOI: 10.1158/1078-0432.CCR-07-4559


Altmetrics provided by Altmetric