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Activity Number:
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263
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Type:
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Contributed
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Date/Time:
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Monday, August 1, 2016 : 2:00 PM to 3:50 PM
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Sponsor:
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Biopharmaceutical Section
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Abstract #319591
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Title:
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Bayesian Adaptive Designs Using Copula-Type Models in Phase I Cancer Trials Using Drug Combination
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Author(s):
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Galen Cook-Wiens* and Mourad Tighiouart and Marcio Diniz and Andre Rogatko
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Companies:
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Cedars-Sinai Medical Center and Cedars-Sinai Medical Center and Cedars-Sinai Medical Center and Cedars-Sinai Medical Center
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Keywords:
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Cancer Phase I trials ;
Maximum tolerated dose ;
Continual reassessment method ;
Escalation with overdose control ;
Drug Combination ;
Copula type models
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Abstract:
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We describe adaptive Bayesian designs in cancer phase I clinical trials with the goal of estimating the maximum tolerated dose (MTD) as a curve in the two-dimensional Cartesian plane. Copula type models are used to describe the relationship between the doses and the probability of dose limiting toxicity (DLT). Trial design proceeds by treating cohorts of three patients simultaneously with three different dose combinations determined using the continual reassessment method and escalation with overdose control. At the end of the trial, an estimate of the MTD curve is proposed as a function of Bayes estimates of the model parameters. We evaluate design operating characteristics in terms of safety of the trial and percent of dose recommendation at dose combination neighborhoods around the true MTD curve. The method is further adapted to the case of a pre-specified discrete set of dose combinations and is compared to a published two dimensional design. We also examine the performance of the approach under model misspecifications for the true dose-toxicity relationship.
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Authors who are presenting talks have a * after their name.
