What is the optimal fit-for-purpose design in an oncology first-in-human trial?: 3+3 vs. Bayesian logistic regression model.

Abstract

Primary goals When designing a clinical trial, the goals must be clearly and specifically defined, and this should guide decision making on the details of the study. The goals of phase 1 oncology studies may include: 1) determine maximal tolerated dose (MTD), 2) provide recommended phase 2 dose (RP2D), 3) describe/characterize dose-limiting toxicity (DLT), 4) expand understanding of the investigational product, e.g. pharmacokinetics, efficacy. These goals may be coupled with business/development timeline (e.g., as quickly as possible) and/or cost goals (with fewest possible subjects). For novel targets or mode of action, these many goals are further complicated by limited information about clinical efficacy and toxicity. The ethical dilemma regarding dose selection has evolved from being centered on limiting the number of patients who experience toxicity to also minimize underdosing of patients in need of treatment.