Comparison of Various Phase I Combination Therapy Designs in Oncology for Evaluation of Early Tumor Shrinkage Using Simulations.

ABSTRACT: There is still a lack of efficient designs for identifying the dose response in oncology combination therapies in early clinical trials. The concentration response relationship can be identified using the early tumor shrinkage time course, which has been shown to be a good early response marker of clinical efficacy. The performance of various designs using an exposure-tumor growth inhibition model was explored using simulations. Different combination effects of new drug M and cetuximab (reference therapy) were explored first assuming no effect of M on cetuximab (to investigate the type I error (α)), and subsequently assuming additivity or synergy between cetuximab and M. One-arm, two-arm, and four-arm designs were evaluated. In the one-arm design, 60 patients received cetuximab + M. In the

SUBMITTER: Seurat J 

PROVIDER: S-EPMC7762808 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature