Phase 0 clinical trials in oncology: a paradigm shift for early drug development?

PURPOSE: To review the potential impact of Phase 0 trials conducted under the United States Food and Drug Administration (FDA) exploratory IND guidance on oncology drug development.
METHODS: The FDA's exploratory IND guidance document is examined in detail and its practical application to specific first-in-human proof of concept clinical studies called Phase 0 trials is discussed.
RESULTS: Phase 0 trials represent a novel strategy for accelerating the development of the next generation of anticancer treatments. Phase 0 studies are conducted prior to conventional toxicity-defined dose-escalation studies and these trials do not explore maximum toxicity levels and by definition are devoid of any therapeutic or diagnostic intent. They require less extensive formulation and non-clinical toxicity testing than conventional first-in-human Phase I trials. This pathway may be valuable in reducing the time and resources required to initiate clinical testing and it may also be useful in guiding the later stages of drug development. Alternatively, the early termination of a less than promising lead compounds could help in selecting the best agents for later clinical development. Possible disadvantages include the ethical challenge of testing non-therapeutic drug regimens in cancer patients and the need to conduct standard dose-escalation Phase I studies later in development.
CONCLUSIONS: The potential of this novel pathway to accelerate drug development makes it worthy of further exploration, and National Cancer Institute has recently completed a Phase 0 trial demonstrating its applicability to targeted anticancer agents.