Identifying a maximum tolerated contour in two-dimensional dose finding.

The majority of phase I methods for multi-agent trials have focused on identifying a single maximum tolerated dose combination (MTDC) among those being investigated. Some published methods in the area have been based on the notion that there is no unique MTDC and that the set of dose combinations with acceptable toxicity forms an equivalence contour in two dimensions. Therefore, it may be of interest to find multiple MTDCs for further testing for efficacy in a phase II setting. In this paper, we present a new dose-finding method that extends the continual reassessment method to account for the location of multiple MTDCs. Operating characteristics are demonstrated through simulation studies and are compared with existing methodology. Some brief discussion of implementation and available software is also provided. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]