Phase 0 Trials in Oncology

Abstract

First-in-human clinical studies (phase I) of new anticancer agents have traditionally focused on determining the maximum tolerated dose and dose-limiting toxicities in patients with cancer. Subsequent phase II and III trials evaluate whether the new agent has potential efficacy. This process is time consuming, expensive, involves potentially hundreds of patients, and has a high rate of failure. To address some of these limitations and facilitate the development and approval of new drugs, the FDA allows phase 0 first-in-human trials to establish whether the investigational agent achieves the desired concentrations and/or modulates its target at clinically achievable concentrations. These trials administer subtherapeutic doses of drug, which are not anticipated to cause toxicity, to a small number of patients for the conduct of pharmacodynamic, pharmacokinetic, or imaging studies. If the agent demonstrates a desirable pharmacokinetic/pharmacodynamic profile, traditional phase I safety and tolerability studies are conducted; otherwise, further clinical development of the agent is unlikely to be justified. This chapter summarizes the key differences between phase 0 and phase I clinical trials.