NCI ET-CTN with Phase i Emphasis at UPCI

描述（由申请人提供）：40多年来，NCI一直支持在美国开展早期临床试验的临床试验基础设施项目。作为加强、促进和加快早期药物开发过程的一部分，NCI创建了NCI实验治疗项目（NExT），它代表了NCI内部和外部团队/机构之间的联合早期治疗开发项目，以优先考虑NCI驱动的靶向治疗管道。NCI现在已经制定了一项综合计划，将NCI赞助的合作实验治疗临床试验项目从一系列独立的机构进行早期癌症治疗试验转变为一个新的综合项目，即NCI实验治疗-临床试验网络（ET-CTN）。匹兹堡大学癌症研究所（UPC）自1990年以来一直是nci指定的综合癌症中心，UPCI自1999年以来一直参与NCI-U01一期早期药物开发计划。我们现在提议成为新的NCI ET-CTN的一部分，作为一个领先的学术组织，具有以下具体目标：(1)使用NCI- ctp IND组合中的单一或组合新药进行早期实验性治疗性临床试验；(2)参与针对特定研究药物的项目组，制定药物开发计划；(3)研究实验制剂的PK/PD方面，建立剂量、剂量、暴露与生物/抗肿瘤效应之间的潜在关系；(4)制定统计学上合适的临床试验设计，包括整体和综合生物标志物试验、加速滴定、适应性设计和其他设计方案；(5)调查肝脏和/或肾功能不全的特殊研究人群；(6)评估基于实验室的有关药物-药物相互作用的研究数据；(7)评估研究药物临床试验的转化终点。

DESCRIPTION (provided by applicant): For more than 40 years, the NCI has supported a clinical trials infrastructure program to conduct early phase clinical trials across the US. As par of its efforts to enhance, facilitate, and expedite the process of early-phase drug development, the NCI created the NCI Experimental Therapeutics Program (NExT), which represents a joint early therapeutics development program between NCI intramural and extramural teams/institutions to prioritize a pipeline of NCI-driven targeted therapeutics. The NCI has now developed a comprehensive plan to transform the NCI-sponsored cooperative experimental therapeutics clinical trials program from a series of separate institutions conducting early-phase cancer treatment trials to a new consolidated, integrated Program, referred to as the NCI Experimental Therapeutics-Clinical Trials Network (ET-CTN). The University of Pittsburgh Cancer Institute (UPC) has been an NCI-designated comprehensive cancer center since 1990, and the UPCI has been involved in the NCI-U01 Phase I Early Drug Development Program since 1999. We now propose to be part of the new NCI ET-CTN as a Lead Academic Organization with the following specific aims: (1) to conduct early-phase experimental therapeutic clinical trials using single or combinations of novel agents from the NCI-CTP IND portfolio; (2) to participate on investigational agent-specific Project Teams to define the drug development plan; (3) to investigate the PK/PD aspects of the experimental agents and establish potential relationships between dose, schedule, exposure, and biological/antitumor effect; (4) to develop statistically appropriate clinical trial designs, including integral and integrated biomarker trials, accelerated titration, adaptive designs, and other design schemes; (5) to investigate special study populations with hepatic and/or renal dysfunction; (6) to evaluate data from related laboratory-based studies that assess drug-drug interactions; and (7) to evaluate translational endpoints in clinical trials of investigational agents.