title: Seamless Phase I/II Adaptive Design for Oncology Trials of Molecularly Targeted Agents.
abstract: 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. In this article, we propose a new early-phase method for trials investigating targeted agents. We provide simulation results illustrating the operating characteristics of our design.
authors.affiliation: a Division of Translational Research & Applied Statistics, Department of Public Health Sciences , University of Virginia , Charlottesville , Virginia , USA.
authors.forename: Nolan A
authors.initials: NA
authors.lastname: Wages
authors.forename: Christopher
authors.initials: C
authors.lastname: Tait
mesh_terms: D000465:Algorithms; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D017321:Clinical Trials, Phase I as Topic / Q000379:methods* / Q000706:statistics & numerical data; D017322:Clinical Trials, Phase II as Topic / Q000379:methods* / Q000706:statistics & numerical data; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D054796:Drug Dosage Calculations; D006801:Humans; D020714:Maximum Tolerated Dose; D015233:Models, Statistical; D058990:Molecular Targeted Therapy / Q000009:adverse effects / Q000706:statistics & numerical data; D009369:Neoplasms / Q000188:drug therapy*; D009716:Numerical Analysis, Computer-Assisted; D012107:Research Design / Q000706:statistics & numerical data; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents
keywords: Continual reassessment method; Dose finding; Molecularly targeted agent; Optimal biological dose