Abstract: Phase 0 trials are designed primarily to evaluate the pharmacodynamic and/or pharmacokinetic properties of selected investigational agents before initiating traditional phase I testing. In a phase 0 trial, the pharmacodynamic effects of an investigational agent are evaluated by a target or biomarker which is measured by an assay established and validated in preclinical models. The phase 0 trial is characterized by a small number of patients enrolled and limited dosing period with a non-therapy-intended dose range. Furthermore, phase 0 trials are classified into three types and conducted under the US Food and Drug Administration exploratory investigational new drug guidance with less preclinical toxicity data than usually required for traditional first-in-human studies. A well designed and executed phase 0 trial can overcome its limitations and has a great potential for improving the efficiency and success of subsequent trials, particularly those evaluating molecularly targeted antitumor candidates.

Key words: phase 0 trial, target, biomarker, exploratory investigational drug, pharmacokinetics, pharmacodynamics