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Implementation of a Model-Based Design in a Phase Ib Study of Combined Targeted Agents.

ABSTRACT: In recent years, investigators have recognized the rigidity of single-agent, safety-only, traditional designs, rendering them ineffective for conducting contemporary early-phase clinical trials, such as those involving combinations and/or biological agents. Novel approaches are required to address these research questions, such as those posed in trials involving targeted therapies. We describe the implementation of a model-based design for identifying an optimal treatment combination, defined by low toxicity and high efficacy, in an early-phase trial evaluating a combination of two oral targeted inhibitors in relapsed/refractory mantle cell lymphoma. Operating characteristics demonstrate the ability of the method to effectively recommend optimal combinations in a high percentage of trials with reasonable sample sizes. The proposed design is a practical, early-phase, adaptive method for use with combined targeted therapies. This design can be applied more broadly to early-phase combination studies, as it was used in an ongoing study of a melanoma helper peptide vaccine plus novel adjuvant combinations. Clin Cancer Res; 23(23); 7158-64. ©2017 AACR.

SUBMITTER: Wages NA

PROVIDER: S-EPMC5712236 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Implementation of a Model-Based Design in a Phase Ib Study of Combined Targeted Agents.

Wages Nolan A NA Portell Craig A CA Williams Michael E ME Conaway Mark R MR Petroni Gina R GR

Clinical cancer research : an official journal of the American Association for Cancer Research 20170721 23

In recent years, investigators have recognized the rigidity of single-agent, safety-only, traditional designs, rendering them ineffective for conducting contemporary early-phase clinical trials, such as those involving combinations and/or biological agents. Novel approaches are required to address these research questions, such as those posed in trials involving targeted therapies. We describe the implementation of a model-based design for identifying an optimal treatment combination, defined by ...[more]

PMID: 28733439

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Implementation of a Model-Based Design in a Phase Ib Study of Combined Targeted Agents.

Publications

Implementation of a Model-Based Design in a Phase Ib Study of Combined Targeted Agents.

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