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Abstract:
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It is common to encounter two-dimensional dose finding in phase I trials, for example, in trials combining multiple drugs, or in single-agent trials that simultaneously search for the maximum tolerated dose and treatment schedule. We propose a simple and adaptive two-dimensional dose-finding design that can accommodate any type of single-agent dose-finding method. In particular, we convert the two-dimensional dose-finding trial to a series of one-dimensional dose-finding subtrials along shortened line search segments by fixing the dose level of one drug, and conduct them sequentially. Based on the MTD obtained from the completed one-dimensional trial, we eliminate the doses that lie outside of the search range based on the partial order, and thereby adaptively and efficiently reduce the two-dimensional dose-finding space. We illustrate the design through extensive simulation studies.
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