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Activity Number:
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620
- Dose-Finding for Monotherapy and Combination Therapy in Oncology and Other Complex Studies
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Type:
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Contributed
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Date/Time:
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Thursday, August 3, 2017 : 8:30 AM to 10:20 AM
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Sponsor:
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Biopharmaceutical Section
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Abstract #322780
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Title:
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Incorporating Pharmacokinetic Assessment in Bayesian Phase I Trial Design in Oncology Area
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Author(s):
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Kentaro Takeda* and Kanji Komatsu and Satoshi Morita
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Companies:
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Astellas Pharma Global Development, Inc. and Astellas Pharma Inc. and Kyoto University Graduate School of Medicine
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Keywords:
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Phase I clinical trial ;
dose-finding ;
Bayesian trial design ;
pharmacokinetic assessment ;
oncology
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Abstract:
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The main purpose of a phase I dose-finding study in oncology area is to estimate the maximum tolerated dose (MTD). Bayesian dose-finding approaches have already been proposed for and implemented in oncology area. A Bayesian continual reassessment method (CRM) is a model-based method based on binary toxicity outcome and fixed dose levels. It has shown that CRM works well under the proportional assumption between dose - exposure relationship. However, if dose - exposure relationship is not proportional, e.g., saturation of drug elimination or drug absorption, it may lead to inappropriate estimation results. In this research work, we propose a Bayesian approach to incorporating pharmacokinetic assessment to estimate MTD for a dose-finding trial to develop an anti-cancer agent. Our proposed approach aims to adaptively incorporate pharmacokinetic assessment to improve the MTD determination. We propose an adjustment standardized dose in statistical model according to the latest area under the time-concentration curve assessment. The simulation results of our proposed method compared with standard approaches are very encouraging across a variety of realistic settings.
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Authors who are presenting talks have a * after their name.
