Dose finding designs for late-onset toxicities

项目摘要/摘要： 目前肿瘤学药物开发的格局正在对被广泛接受的 用于剂量发现临床试验的方法。这些试验中最大的挑战之一是 当相关毒性事件发生时，确定适当的推荐第二阶段剂量(RP2D) 发生在后来的治疗周期中。被接受的剂量发现方法旨在用于 在治疗过程的早期观察到哪些毒性，它们可能不适合于 设计具有超越早期治疗周期的相关毒性的可能性的研究。 因此，FDA登记的许多新疗法的剂量不同于 在第一阶段确定的是，越来越需要新的研究设计来解决临床 这些新的治疗范例所产生的现实和统计考虑。因此，目标是 这项建议的目的是开发新的剂量发现方法，解释迟发性毒性。 指导剂量分配，更准确地定义治疗的总体耐受性。

Project Summary / Abstract: 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.