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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 #319677
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Title:
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Dose Finding for Drug Combination in Early Cancer Phase I Trials using Conditional Continual Reassessment Method
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Author(s):
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Quanlin Li* and Mourad Tighiouart and Marcio Diniz
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Companies:
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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 ;
Dose limiting toxicity
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Abstract:
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We propose a new Bayesian adaptive design for cancer phase I clinical trials using two cytotoxic agents. Parametric 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 receiving different dose combinations by either escalating/de-escalating one or both agents. At the end of the trial, we estimate the MTD curve 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 and compare the approach to escalation with overdose control. The method is further adapted to the case of a pre-specified discrete set of dose combinations and is compared to a previously 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.
