An overview of the optimal planning, design, and conduct of phase I studies of new therapeutics.

Phase I clinical trials represent the first step in bringing promising new treatments from the laboratory to the clinic. Although the importance of phase I clinical trials is widely recognized, there is currently no consensus among the scientific, medical, and statistical communities on how best to do these studies in humans. With the advent of targeted therapies, it has become evident that we need to tailor the design of phase I studies for the particular drug class under investigation and any endpoints that are being defined. The National Cancer Institute (NCI) Investigational Drug Steering Committee (IDSC) provides broad external scientific and clinical input on the design and prioritization of early-phase clinical trials with agents for which the NCI Cancer Therapy Evaluation Program (CTEP) holds an Investigational New Drug (IND) application through the U.S. Food and Drug Administration (FDA). The IDSC has formed a number of task forces and working groups, including the Clinical Trial Design Task Force and the Biomarker Working Group, many with membership from within the IDSC as well as external experts, including participants from academia, the pharmaceutical industry, and regulatory authorities. The Clinical Trials Design Taskforce sponsored a Phase I Workshop with the primary goal being to develop consensus recommendations for the optimal design of phase I studies. The primary focus included (1) efficient trial designs, (2) phase I drug combinations, and (3) appropriate statistical and correlative endpoints. In this CCR Focus series, articles summarize key aspects and recommendations on phase I studies (including combination trials), such as design, use of biomarkers, the European Union and Japanese perspectives on design, requirements for first-in-human and other phase I studies, and ensuring regulatory and International Conference on Harmonization (ICH) compliance. A final article summarizes recommendations for the design and conduct of phase II studies.