The current landscape of oncology drug development is posing a challenge to widely-accepted methods used in dose-finding clinical trials. One of the biggest challenges in these trials is identifying an appropriate recommended Phase II dose (RP2D) when relevant toxicity events occur in later cycles of therapy. Accepted dose finding methods were intended for use in trials in which toxicity is observed early on in the treatment course, and they may not be appropriate for designing studies with the potential for pertinent toxicities beyond early cycles of therapy. Consequently, many novel therapies are registered by the FDA at doses different than those identified in Phase I. There is a growing need for new study designs that address the clinical realities and statistical considerations arising by these new treatment paradigms. Thus, the goal of this proposal is to develop novel dose-finding methods that account for late-onset toxicities in guiding dose allocation and to more accurately define the overall tolerance of the treatment.
One of the biggest challenges in Phase I clinical trials is identifying an appropriate recommended Phase II dose when relevant toxicity events occur in later cycles of therapy. Current treatments are being administered over extended periods of time, which results in relevant toxicity events occurring outside of a short-term evaluation window. There is a growing need to develop Phase I methods that make efficient use of modern safety profiles involving late-onset toxicity, leading to more optimal dosing and patient outcomes.
