Vanderbilt Phase I Translational Research Program

范德比尔特第一阶段转化研究计划

• 批准号: 6581808
• 负责人: MACE L ROTHENBERG
• 金额: $ 11.5万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-14 至 2008-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6581808
• 关键词: antineoplastics; biopsy; clinical research; clinical trial phase I; cooperative study; drug administration rate /duration; drug adverse effect; drug screening /evaluation; epidermal growth factor; high performance liquid chromatography; human subject; human therapy evaluation; mass spectrometry; microarray technology; neoplasm /cancer chemotherapy; neoplasm /cancer pharmacology; patient oriented research; pharmacokinetics; prostaglandin endoperoxide synthase

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.

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）和梅哈里医学中心（MMC）的联合努力，以扩大正在进行的I期临床研究的努力，并建立I期转化研究计划。本提案的目标是开展新的抗癌药物的早期阶段，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。该项目汇集了在早期临床试验中经验丰富的临床研究人员和范德比尔特大学的基础科学家，他们正在研究分子生物学，如EGFR和COX-2，这是一些最有前途的分子靶向治疗的重点。这些研究人员一起工作，利用互补的技能和兴趣来设计和发起创新的转化研究。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提供的优秀资源将促进新药物早期临床试验中使用假设检验和假设生成方法的药物遗传学分析的扩展。药效学关系将探讨使用PK和PG数据。本文提供的数据突出了范德比尔特I期研究的最新成就，并确定了在该合作协议下每年开展2-3项转化研究所需的患者资源的充分性。在过去的4年里，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。数据还展示了范德比尔特第一阶段项目在美国东南部的区域影响，该地区目前没有nci指定的第一阶段中心。我们描述了MMC在合作协议中逐步参与的计划，这将提高非裔美国患者进入I期临床试验的机会，并使Meharry的临床和基础研究人员参与这些早期转化研究的设计和实施。总之，我们相信这项合作协议的支持将大大加强我们对重要抗癌新药的临床、药理学和分子影响的了解，并优化其进一步的开发和利用。