Repeated measures dose-finding design with time-trend detection in the presence of correlated toxicity data

• Published in: Clinical trials (London, England) Vol. 14; no. 6; p. 611
• Main Authors: Yin, Jun, Paoletti, Xavier, Sargent, Daniel J, Mandrekar, Sumithra J
• Format: Journal Article
• Language: English
• Published: England 01.12.2017
• Subjects: Antibiotics, Antineoplastic - adverse effects; Antibiotics, Antineoplastic - toxicity; Antineoplastic Agents - toxicity; Bayes Theorem; Clinical Trials, Phase I as Topic - methods; Depsipeptides - adverse effects; Depsipeptides - toxicity; Dose-Response Relationship, Drug; Endpoint Determination - methods; Humans; Immunotherapy - adverse effects; Linear Models; Longitudinal Studies; Maximum Tolerated Dose; Molecular Targeted Therapy - adverse effects; Neoplasms - drug therapy; molecularly targeted agents; adaptive; maximum tolerated dose; correlated toxicity; immunotherapy; Dose-finding; continual reassessment method; time trend; phase I clinical trials; repeated measures

Phase I trials are designed to determine the safety, tolerability, and recommended phase 2 dose of therapeutic agents for subsequent testing. The dose-finding paradigm has thus traditionally focused on identifying the maximum tolerable dose of an agent or combination therapy under the assumption tha...