Dose finding designs for late-onset toxicities

项目概要/摘要： 目前的肿瘤药物开发前景对广泛接受的 剂量探索临床试验中使用的方法。这些试验中最大的挑战之一是 当发生相关毒性事件时，确定适当的推荐II期剂量（RP 2D） 发生在治疗的后期。可接受的剂量探索方法预期用于以下试验： 在治疗过程的早期观察到毒性，并且它们可能不适合于 设计具有超出早期治疗周期的潜在相关毒性的研究。 因此，FDA注册的许多新疗法的剂量不同于那些 在第一阶段确定。越来越需要新的研究设计，以解决临床 这些新的治疗范例所引起的现实和统计考虑。因此，目标 这项提议的一个重要目的是开发新的剂量发现方法， 指导剂量分配并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.