An adaptive dose-finding design based on both safety and immunologic responses in cancer clinical trials.

ABSTRACT: Dose-finding in cancer clinical trials has been dominated by algorithmic designs on the principle that the highest tolerable dose is also the most effective dose. This assumption no longer applies to the biologic treatments that are characterized by different toxicity and/or efficacy profiles to the extent that the best therapeutic dose might be well below any dose that produces serious toxicity. As such, we propose a two-stage design with focus on immunotherapy trials, incorporating both safety and efficacy information. The 1^st stage establishes the safety profile of each dose, with escalation decisions based on likelihood principles. Continuous immunologic outcomes are used to evaluate the relative efficacy of the doses. The 2^nd stage employs an adaptive randomizati

SUBMITTER: Chiuzan C 

PROVIDER: S-EPMC6277027 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature