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Activity Number:
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243
- Contributed Poster Presentations: Biopharmaceutical Section
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Type:
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Contributed
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Date/Time:
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Monday, July 31, 2017 : 2:00 PM to 3:50 PM
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Sponsor:
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Biopharmaceutical Section
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Abstract #323177
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Title:
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Drug Combination Dose Allocation Using Minimal Sets and Coherence in Partially Ordered Sets in Phase I Cancer Trials
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Author(s):
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Galen Cook-Wiens* and Matthieu Clertant and Mourad Tighiouart
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Companies:
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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 ;
Drug combination ;
Dose Limiting Toxicity ;
Coherence ;
Partial Ordering
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Abstract:
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We propose an adaptive design for early phase drug combination trials with the goal of estimating the maximum tolerated dose (MTD) contour. A parametric model is used to describe the dose combination and probability of dose limiting toxicity (DLT) relationship. At each step of the trial, the MTD contour is estimated using the updated model. A minimal set of dose combinations is then constructed by collecting doses that are closest to this contour according to the partial ordering principle. For safety reasons, we extend the concept of coherence to drug combinations in order prevent aggressive dose escalation. Given this last constraint, patients in each cohort are then allocated to doses in the minimal set that do not have high estimated probability of DLT. At the end of the trial a set of dose combinations is recommended as the MTD. We evaluate design operating characteristics in terms of safety of the trial and percent of dose recommendation at the true set of MTDs.
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Authors who are presenting talks have a * after their name.
