Vanderbilt Phase I Translational Research Program

描述（由申请人提供）：本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）以及最终的Meharry医学中心（MMC）的联合努力，以扩大I期临床研究的持续努力并建立I期转化研究计划。该提案的目标是对新抗癌药物进行早期剂量范围试验，以表征其毒性和药理学，并探索其对分子靶点的影响，为药物作用机制和反应决定因素提供新的科学见解。该计划汇集了在早期临床试验中经验丰富的临床研究人员与范德比尔特的基础科学家，他们正在研究EGFR和考克斯-2等分子的生物学，这些分子是一些最有前途的分子靶向治疗的重点。这些研究人员共同努力，利用互补的技能和兴趣来设计和启动创新的翻译研究。新化合物的药代动力学分析将使用高灵敏度和特异性的药物定量方法进行，包括WLC、LCMS和GCMS方法。VICCC和VUMC的优秀资源将促进使用假设检验和假设生成方法的新药早期临床试验中药物遗传学分析的扩展。将使用PK和PG数据探索药效学关系。数据突出了最近在范德比尔特的第一阶段工作的成就，并建立了足够的病人资源，需要进行2-3个转化研究，每年根据本合作协议。在过去的4年中，开放的研究数量增加了63%，入组的患者数量增加了38%，将患者纳入I期研究的医生数量增加了一倍多，撰写和主持I期试验的医生数量增加了一倍。数据还表明，范德比尔特的第一阶段计划在美国东南部，目前没有一个国家癌症研究所指定的第一阶段中心的区域影响。我们描述了我们的计划，MMC在这一合作协议，将提高非洲裔美国患者的访问I期临床试验和参与临床和基础研究人员从Meharry在设计和进行这些早期阶段的转化研究参与的毕业参与。总之，我们相信，这项合作协议的支持将大大加强我们的努力，以了解重要的新抗癌药物的临床，药理学和分子影响，并优化其进一步开发和利用。

DESCRIPTION (provided by applicant): 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 WLC, LCMS, and GCMS 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 I 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 I trials. Data is also presented demonstrating the regional impact of Vanderbilt's 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 anticancer agents and optimize their further development and utilization.