Curve-free phase I/II clinical trial designs for molecularly targeted agents and immunotherapy

Indiana University Indianapolis, Indianapolis IN

Investigators

Linked publications & trials

Abstract

Project Summary/Abstract The primary goal of this proposal is to develop transparent, ?exible and ef?cient phase I/II clinical trial designs identifying optimal doses for molecularly targeted agents (MTA) and immunotherapy (IT). Conventional phase I/II clinical trial designs often use sophisticated parametric models to characterize the joint toxicity-ef?cacy distribu- tions and to conduct the trials. However, the parametric models are hard to justify in practice, and misspeci?cation of parametric models can lead to substantially undesirable performances of phase I/II trials. Moreover, it is dif?cult for the physicians conducting the trials to clinically interpret the parameters of these sophisticated models, and such great learning costs impede the translation of novel statistical designs into real-world trial implementation. To solve these issues, in this proposal we will propose transparent curve-free phase I/II clinical trial designs. The proposed designs make no parametric assumptions on either dose-response relationship or toxicity-ef?cacy correlation and therefore performs robustly under any clinically meaningful dose-response curves. The concise clinically interpretable model expression and dose-?nding algorithm make the proposed designs highly transla- tional from the statistical community to the clinical community. The proposed designs are also highly ?exible because they are applicable for both single-agent trial and drug-combination trial with either quickly observable outcomes or delayed outcomes. The preliminary simulation studies show that the proposed designs are highly ef?cient in optimal dose selection and patient allocation. In addition, we will develop user-friendly web apps to facilitate the widespread application of the proposed designs in clinical practice.