Early-phase Dose-finding Designs for Bivariate Outcomes

In dose-finding trials of chemotherapeutic agents, the goal of identifying the maximum tolerated dose is usually determined by considering information on toxicity only, with the assumption that the highest safe dose also provides the most promising outlook for efficacy. Trials of molecularly targeted agents challenge accepted dose-finding methods because minimal toxicity may arise over all doses under consideration and higher doses may not result in greater response. A class of new early-phase method for trials investigating targeted agents will be presented. Simulation results and theoretical properties are provided to illustrate the operating characteristics of the designs.