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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 #324483
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Title:
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Design of Drug Combination Early Phase Cancer Trials Using Time to Toxicity Data
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Author(s):
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Marcio Diniz* and José Jimenez and Andre Rogatko and Mourad Tiguiouart
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Companies:
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Cedars Sinai Medical Center and Politecnico di Torino and Cedars Sinai Medical Center and Cedars Sinai Medical Center
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Keywords:
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Cancer phase I trials ;
Continuous dose ;
Continual reassessment method ;
Escalation with overdose control ;
Drug combination ;
Time to toxicity
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Abstract:
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We propose an adaptive design for allocating dose combinations to cancer patients in early phase trials in the presence of late onset dose limiting toxicity (DLT). Time to DLT is modeled as a function of dose combinations and their interaction term using the cure rate model with a Weibull baseline hazard function. Trial design proceeds by treating patients as they arrive where at each stage of the trial, we seek a dose of one agent using the posterior distribution of the maximum tolerated dose (MTD) of this agent given the current dose of the other agent. These doses are estimated using two different methods: the continual reassessment method (CRM) and escalation with overdose control (EWOC). At the end of the trial, we estimate MTD curve as a function of Bayes estimates of the model parameters. The methodology is assessed using extensive simulations in the settings of continuous and discrete dose levels.
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Authors who are presenting talks have a * after their name.
