Dose-Finding with Two Agents in Phase I Oncology Trials

Authors: Thall P.F.¹; Millikan R.E.²; Mueller P.¹; Lee S-J.¹

Source: Biometrics, Volume 59, Number 3, September 2003 , pp. 487-496(10)

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Abstract:

Summary.

We propose an adaptive two-stage Bayesian design for finding one or more acceptable dose combinations of two cytotoxic agents used together in a Phase I clinical trial. The method requires that each of the two agents has been studied previously as a single agent, which is almost invariably the case in practice. A parametric model is assumed for the probability of toxicity as a function of the two doses. Informative priors for parameters characterizing the single-agent toxicity probability curves are either elicited from the physician(s) planning the trial or obtained from historical data, and vague priors are assumed for parameters characterizing two-agent interactions. A method for eliciting the single-agent parameter priors is described. The design is applied to a trial of gemcitabine and cyclophosphamide, and a simulation study is presented.

Keywords: Adaptive design; Bayesian design; Dose-finding; Phase I clinical trial

Document Type: Research article

DOI: http://dx.doi.org/10.1111/1541-0420.00058

Affiliations: 1: Department of Biostatistics, Box 447, University of Texas, M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, U.S.A. 2: Department of Genitourinary Medical Oncology, Box 422, University of Texas, M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, U.S.A.

Publication date: 2003-09-01