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. <p>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.
- Received April 12, 2017.
- Revision received May 15, 2017.
- Accepted July 13, 2017.
- Copyright ©2017, American Association for Cancer Research.