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Activity Number:
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139
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Type:
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Topic Contributed
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Date/Time:
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Monday, August 7, 2006 : 10:30 AM to 12:20 PM
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Sponsor:
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Biometrics Section
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| Abstract - #305800 |
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Title:
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Adaptive Phase I Clinical Trial Designs for Biologic Agents and Molecularly Targeted Therapies
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Author(s):
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Sumithra Mandrekar*+ and Daniel Sargent
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Companies:
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Mayo Clinic College of Medicine and Mayo Clinic College of Medicine
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Address:
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Division of Biostatistics, Rochester, MN, 55905,
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Keywords:
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phase I ; CRM ; targeted therapy
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Abstract:
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Agents with specific biologic targets with unknown dose efficacy curves and limited toxicity profile require novel designs to establish biologically optimal doses. We present two designs for identifying an optimal dose of a single or two drug combinations utilizing both toxicity and efficacy data. A continual reassessment method with straight forward dose selection criteria using accumulated data from all patients treated thus far is employed based on the flexible continuation-ratio model. In a two-agent setting, a generalization of the single agent model allowing for separate toxicity and efficacy curves for each agent to generate a dose outcome surface for the combination is used. Our simulations demonstrated that the proposed designs have favorable operating characteristics in terms of experimentation and recommendation rates and the average sample size under a variety of scenarios.
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