A comparative study of adaptive dose-finding designs for phase I oncology trials of combination therapies.

Little is known about the relative performance of competing model-based dose-finding methods for combination phase I trials. In this study, we focused on five model-based dose-finding methods that have been recently developed. We compared the recommendation rates for true maximum-tolerated dose combinations (MTDCs) and over-dose combinations among these methods under 16 scenarios for 3 × 3, 4 × 4, 2 × 4, and 3 × 5 dose combination matrices. We found that performance of the model-based dose-finding methods varied depending on (1) whether the dose combination matrix is square or not; (2) whether the true MTDCs exist within the same group along the diagonals of the dose combination matrix; and (3) the number of true MTDCs. We discuss the details of the operating characteristics and the advantages and disadvantages of the five methods compared.