NCI ET-CTN with Phase i Emphasis at UPCI

描述(由申请人提供)：40多年来，NCI一直支持在全美进行早期临床试验的临床试验基础设施计划。作为加强、促进和加快早期药物开发进程的努力的一部分，NCI创建了NCI实验治疗计划(NEXT)，该计划代表了NCI内部和外部团队/机构之间的联合早期治疗开发计划，以优先考虑NCI驱动的靶向治疗流水线。NCI现在已经制定了一项全面的计划，将NCI赞助的合作实验疗法临床试验计划从一系列进行早期癌症治疗试验的独立机构转变为一个新的综合计划，称为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年以来一直是美国国家癌症研究所指定的综合性癌症中心，自1999年以来一直参与NCI-U01第一阶段早期药物开发计划。我们现在提议成为新的NCI ET-CTN的一部分，作为领导学术组织的一部分，具体目标如下：(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临床试验；(2)参与特定于研究试剂的项目团队，以确定药物开发计划；(3)调查实验试剂的PK/PD方面，并建立剂量、时间表、暴露和生物/抗肿瘤效应之间的潜在关系；(4)开发统计上合适的临床试验设计，包括整体和综合生物标记物试验、加速滴定、适应性设计和其他设计方案；(5)调查肝和/或肾功能不全的特殊研究人群；(6)评估 来自评估药物-药物相互作用的相关实验室研究的数据；以及(7)评估研究药物临床试验中的翻译终点。 相关性：作为NCI实验治疗临床试验网络的主要学术组织，UPCI计划利用其在早期临床药物开发方面的重要经验和领导地位，促进对NCI和国家利益具有高度优先地位的新型治疗药物和组合的早期临床开发。这一努力的长期目标是指导未来的疾病特异性临床试验，这些试验可能会改变美国和全世界的癌症护理标准

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. RELEVANCE: As a Lead Academic Organization of the NCI Experimental Therapeutics Clinical Trials Network, the UPCI plans to leverage its significant experience and leadership in early-phase clinical drug development and facilitate the early-phase clinical development of novel therapeutic agents and combinations that are of high priority to the NCI and the national interest. The long-term goal of this effort is to guide future disease specific clinical trials tha may have the potential to change the standard of cancer care in the US and worldwide