Phase I Molecular and Clinical Pharmacodynamic Trials ET-CTN

描述(由申请人提供)：本UM1合作协议的目的是支持由三个国家癌症研究所(NCL)指定的癌症中心组成的财团参与一个整合的NCI实验治疗-临床试验网络(ET-CTN)，以进行早期实验治疗临床试验。由希望之城综合癌症中心(COH，“牵头学术组织”[LAO])、南加州大学(USC)/诺里斯综合癌症中心(USC，准组织[AO])和加州大学戴维斯癌症中心(UCD，AO)组成的联合体作为一个多学科团体，根据UOL合作协议和NOI合同，进行NCI赞助的研究性新药(IND)的早期实验疗法临床试验，已有20年的历史。除了在我们自己的联盟内工作外，我们还与其他U01和N01患者建立了合作安排，以利用他们的特定专业知识，更高效地完成临床试验。我们的联盟将联合COH、USC和UCD在分子药理学、药代动力学、药效学、药物基因组学、信号转导、细胞周期调节、非侵入性成像和生物信息学领域的专业知识，为ET-CTN制剂特定的跨网络药物开发团队提供帮助，以进行创新的、实验室指导的早期发育和药物动力学研究。这些早期研究不仅将导致分配推荐的生物有效的第二阶段剂量，并了解针对新的分子途径的特定抗肿瘤药物的正常组织毒性谱，而且还将提供对关键肿瘤细胞靶点的药物作用的机械验证，将与药物相关的肿瘤和宿主生物标记物的变化与临床结果相关联，并在实验室和临床对化合物的治疗作用机制发展新的见解。因此，他们将推进ET-CTN的总体目标，以定义开发新型抗癌药物的更好方法，这些方法利用从分子上表征肿瘤的能力，并找到适当的生物标记物来选择最有可能对特定药物有反应的患者。

DESCRIPTION (provided by applicant): The purpose of this UM1 Cooperative Agreement is to support participation by a consortium of three National Cancer Institute (NCl)-Designated Cancer Centers in a consolidated, integrated NCI Experimental Therapeutics-Clinical Trials Network (ET-CTN) to conduct early phase experimental therapeutics clinical trials. The Consortium of the City of Hope Comprehensive Cancer Center (COH, the "Lead Academic Organization," [LAO]), The University of Southern California (USC)/Norris Comprehensive Cancer Center (USC, Associate Organization [AO]) and the University of California, Davis Cancer Center (UCD, AO) has a 20-year history as a multidisciplinary group conducting early phase experimental therapeutics clinical trials of NCI-Sponsored Investigational New Drugs (INDs) under UOl Cooperative Agreements and NOI Contracts. In addition to working within our own Consortium, we have developed collegial arrangements with other U01 and N01 holders to take advantage of their specific expertise and more efficiently complete clinical trials. Our consortium will contribute to ET-CTN agent-specific trans-network drug development teams from the combined expertise of COH, USC, and UCD in the areas of molecular pharmacology, pharmacokinetics, pharmacodynamics, pharmacogenomics, signal transduction, cell cycle regulation, non-invasive imaging, and bioinformatics to conduct innovative, laboratory-directed early phase developmental and pharmacokinetic studies. These early phase studies will lead not only to the assignment of a recommended, biologically effective Phase II dose, and to an understanding of the spectrum of normal tissue toxicity for specific antineoplastic agents that are directed against novel molecular pathways, but will also provide a mechanistic validation of the effects of the agents on critical tumor cell targets, correlate drug-related alterations of tumr and host biologic markers with clinical outcome, and develop new insights into the therapeutic mechanism of action of the compounds both in the laboratory and the clinic. As such, they will advance the ET-CTN overall goal to define better approaches to the development of novel anticancer agents that capitalize on the ability to characterize tumors molecularly and find appropriate biomarkers to select patients most likely to respond to specific agents.