Statistical justification of expansion cohorts in phase 1 cancer trials.

ABSTRACT:

Background

Phase I cancer trials increasingly incorporate dose-expansion cohorts (DECs), reflecting a growing demand to acquire more information about investigational drugs. Protocols commonly fail to provide a sample-size justification or analysis plan for the DEC. In this study, we develop a statistical framework for the design of DECs.

Methods

We assume the maximum tolerated dose (MTD) for the investigational drug has been identified in the dose-escalation stage of the trial. We use the 80% lower confidence bound and the 90% upper confidence bound for the response and toxicity rates, respectively, as decision thresholds for the dose-expansion stage. We calculate the operating characteristics with reference to prespecified minimum effective response rates and maximum safe

SUBMITTER: Mokdad AA 

PROVIDER: S-EPMC6108930 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature