Designing combination drug phase I trials has become increasingly complex, due to the increasing diversity in classes of agents, mechanisms of action, safety profiles and drug-administration schedules. With approximately 850 agents currently in development for cancer treatment, it is evident that combination development must be prioritised, as based on a specific hypothesis, as well as a projected development path for the involved combination. In this manuscript the most relevant issues and pitfalls for combination drug phase I trial design are discussed. Several phase I study designs that incorporate controls to circumvent bias due to imbalances in observed background toxicity are discussed.

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doi.org/10.1016/j.ejca.2010.07.002, hdl.handle.net/1765/21735
European Journal of Cancer
Erasmus MC: University Medical Center Rotterdam

Hamberg, P., Ratain, M., Lesaffre, E., & Verweij, J. (2010). Dose-escalation models for combination phase i trials in oncology. European Journal of Cancer (Vol. 46, pp. 2870–2878). doi:10.1016/j.ejca.2010.07.002