Phase 1 Oncology Clinical Trials for Related Subpopulations: The Power Walk Design

Abstract

Motivcrtion/Background: This paper addresses designing a Phase 1 trial where the doseresponse curve differs across patient subpopulations. We examine a design which "power walks" through clinically ineffective dose levels, accruing from either subpopulation, until dose limiting toxicity appears. The design then splits into two Phase 1 trials for each subpopulation. Methods/Results:We performed simulation studies of I0000 Phase 1 trials comparing the "power walk" design to the alternatives. The power walk design correctly estimates the maximum tolerated dose (MTD) up to 20% more ojien. The power walk design performs best with a steep dose-response curve, and overestimates the MTD roughly 10% of the time. Conclusions:The power walk design is appropriate to obtain MTDs for separate patient subpopulations where the initial dose is clinically ineffective or substantially below the MTD. A power walk design study involves fewer patients and achieves the correct MTD more ofen. The power walk design is not recommended when the initial dose level is near the MTD.

Adaptive clinical trial designs for phase I cancer studies

“…Storer [26,27] was one of the first to explore statistical properties of the 3+3 design and proposed a few modifications, called "up-and-down designs". Several other practical modifications of the 3+3 design were proposed [28,29,30,31].…”