Vanderbilt Phase I Translational Research Program

这份提案描述了范德比尔特-英格拉姆综合癌症中心(VICCC)、 范德比尔特大学医学中心(VUMC)，并最终扩展到Meharry医学中心(MMC) 正在进行一期临床研究，并建立一期转化研究计划。这样做的目的是 提议进行新抗癌剂的早期阶段、剂量范围的试验，以确定其毒性和 以及探索它们对分子靶点的影响，以提供对药物的新的科学见解 作用机制和反应的决定因素。该计划汇集了在以下领域经验丰富的临床研究人员 与范德比尔特的基础科学家进行早期临床试验，他们正在研究EGFR等分子的生物学 和COX-2，这是一些最有希望的分子靶向治疗的重点。一起工作，这些人 研究人员利用互补的技能和兴趣来设计和启动创新的翻译 研究性研究。新化合物的药代动力学分析将使用高度敏感和特异的 药物定量方法包括高效液相色谱法、液质联用法和气质联用法。网站上提供的优秀资源 VICCC和VUMC将推动在新的早期临床试验中扩大药物遗传学分析 使用假设检验和假设生成方法的代理。药效学关系将是 探索了使用PK和PG数据。提供的数据突出了该阶段的最新成就！努力在 Vanderbilt和建立开展2-3项转化性研究所需的患者资源的充分性 在这份合作协议下，我们将在一年内。在过去的4年里，研究的数量增加了63%。 开放，登记的患者数量增加了38%，进入的医生数量增加了一倍多 患者进入I期研究，撰写和主持t期试验的医生数量翻了一番。数据是 还展示了Vanderbilars第一阶段计划在美国东南部的区域影响，以及 目前没有NCI指定的第一阶段中心的地区。我们描述了我们对MMC逐步参与的计划 在这项合作协议中，将加强非裔美国患者参加I期临床试验的机会 以及来自Meharry的临床和基础研究人员参与这些早期阶段的设计和实施 翻译研究研究。总之，我们相信，这项合作协议的支持将 显著增强我们了解重要新技术的临床、药理学和分子影响的努力 抗癌药物，优化其进一步开发利用。

This proposal describes a combined effort of the Vanderbilt-Ingram Comprehensive Cancer Center (VICCC), the Vanderbilt University Medical Center (VUMC) and, eventually, the Meharry Medical Center (MMC), to expand ongoing efforts in Phase I clinical research and establish a Phase I Translational Research Program. The goals of this proposal are to conduct early phase, dose-ranging trials of new anticancer agents to characterize their toxicity and pharmacology as well as to explore their effects on molecular targets to provide new scientific insights into drug mechanisms of action and determinants of response. The Program brings together clinical investigators experienced in early phase clinical trials with basic scientists at Vanderbilt who are studying the biology of molecules, such as EGFR and COX-2, that are the focus of some of the most promising molecularly-targeted therapies. Working together, these researchers have taken advantage of complementary skills and interests to design and initiate innovative translational research studies. Pharmacokinetic analysis of novel compounds will be performed using highly sensitive and specific methods of drug quantitation including HPLC, LC/MS, and GC/MS methodology. The excellent resources available at VICCC and VUMC will promote the expansion of pharmacogenetic analyses in early phase clinical trials of novel agents using hypothesis-testing as well as hypothesis-generating approaches. Pharmacodynamic relationships will be explored using PK as well as PG data. Data is presented that highlight recent accomplishments of the Phase ! effort at Vanderbilt and establish the adequacy of patient resources needed to carry out 2-3 translational research studies per year under this cooperative agreement. Over the past 4 years there has been a 63% increase in the number of studies open, a 38% increase in the number of patients enrolled, more than a doubling of the number of physicians entering patients into Phase I studies, and a doubling of the number of physicians writing and chairing Phase t trials. Data is also presented demonstrating the regional impact of Vanderbilrs Phase I program in the Southeast United States, an area currently without an NCI-designated Phase I center. We describe our plan for the graduated involvement of MMC in this cooperative agreement that will enhance both the access of African-American patients to Phase I clinical trials and the involvement of clinical and basic researchers from Meharry in the design and conduct of these early phase translational research studies. In summary, we believe that the support from this cooperative agreement will significantly enhance our efforts to understand the clinical, pharmacologic, and molecular impact of important new anficancer agents and optimize their further development and utilization.