Therapy Evaluation Core

项目说明/抽象治疗评估核心 我们的脑瘤治疗创新中心的目标是只提名最有希望的 晚期临床试验的新治疗策略。这将通过仔细的临床前准备工作来实现。 评价脑肿瘤合理分布的潜在候选药物，优化剂量和方案 用于联合用药，并进行严格的疗效分析。结合仔细评估 药代动力学(PK)和药效学(PD)，这些研究将被用来建立PK→PD→疗效 模型，以预测新方案是否可能在人基底膜中具有足够的分布和疗效。 这些预测随后将在0/I期临床试验中进行测试，在这些临床试验中，安全性、耐受性、药物分布 并将测试目标上的效果。将人力PK/PD数据集成到我们的模型中，然后将用于帮助 为是否将特定的新疗法转移到更高级的II期或III期临床提供决策信息 试探性测试。为了实现这一目标，治疗评价核心和药理学核心将密切合作 支持在这些项目和更广泛的胶质母细胞瘤治疗网络内进行的研究 (GTN)。治疗评价核心的工作范围可归类为下述两个目标。 具体目标1：在荷瘤动物中开发、管理和执行体内研究 具体目标2：开发和管理早期临床试验研究

PROJECT DESCRIPTION/ABSTRACT – THERAPY EVALUATION CORE The goal of our Center of Innovation for Brain Tumor Therapeutics is to nominate only the most promising novel treatment strategies for late-stage clinical testing. This will be accomplished through careful pre-clinical evaluation of potential drug candidates for adequate brain tumor distribution, optimization of dose and schedule for combinatorial regimens, and rigorous efficacy analyses. Combined with careful evaluation of pharmacokinetics (PK) and pharmacodynamics (PD), these studies will be used to establish a PK→PD→efficacy model to predict whether the novel regimen is likely to have adequate distribution and efficacy in human GBM. These predictions then will be tested in Phase 0/I clinical trials in which the safety, tolerability, drug distribution and on-target effects will be tested. Integration of human PK/PD data into our model then will be used to help inform decision making for whether to move specific novel therapies into more advanced Phase II or III clinical trial testing. To accomplish this, the Therapy Evaluation Core and the Pharmacology Core will work closely to support the research being performed within the Projects and the broader Glioblastoma Therapeutics Network (GTN). The scope of work for the Therapy Evaluation Core can be categorized in the two aims described below. Specific Aim 1: Develop, manage and execute in vivo studies in tumor-bearing animals Specific Aim 2: Develop and manage early-phase clinical trial studies