PITT-CAL ETCTN PK Resource Laboratory

摘要 该U24合作协议目的是支持由两个国家癌症研究所组成的财团 (NCI)-指定的全面癌症中心资助的药代动力学(PK)核心实验室已加入 共同作为NCI实验治疗-临床试验的整合PK资源 网络(ETCTN)。UPMC Hillman癌症中心(HCC)癌症药代动力学和 药效学设施和希望之城(COH)分析药理核心设施为国家 因其在抗癌药物的药理学表征方面的领先地位而受到认可。新组建的 PIT-CAL ETCTN PK资源实验室(PIT-CAL)建议对ADME配置文件进行系统评估 CTEP药物在临床开发的不同阶段通过完成以下工作 目标：(1)将药理学专业知识应用于ETCTN的早期药物开发工作，协助 研究设计和其他与PK相关的活动；(2)对生物样本进行定量分析；以及 (3)进行非分区、分区和总体PK分析，并将结果报告给研究 及时与团队和CTEP合作。我们的方法将是利用我们的技术和科学专长来领导 所有与PK相关的活动，并将这些PK调查与其他临床和相关研究相结合 在药物开发过程中执行。我们将开发、验证和实施准确、精确、 以及用于研究血浆、组织和其他生物样本中的药物和代谢物的灵敏分析，以及 分析ETCTN LOAS的临床样本。最后，我们将导出PK参数来表征 ETCTN试验中药物的ADME，将这些结果与药物反应的药效学测量相结合 并向CTEP和临床团队报告，以最佳方式告知正在进行的和未来的CTEP药物开发 以及它们的组合。

SUMMARY The purpose of this U24 Cooperative Agreement is to support a consortium of two National Cancer Institute (NCI)-Designated Comprehensive Cancer Center-funded pharmacokinetic (PK) core labs that have joined together as a consolidated, integrated PK resource for the NCI Experimental Therapeutics-Clinical Trials Network (ETCTN). The UPMC Hillman Cancer Center (HCC) Cancer Pharmacokinetics and Pharmacodynamics Facility and City of Hope (COH) Analytical Pharmacology Core Facility are nationally recognized for their leadership in the pharmacological characterization of anticancer agents. The newly formed PITT-CAL ETCTN PK Resource Laboratory (PITT-CAL) proposes to systematically evaluate the ADME profiles of CTEP agents in various phases of clinical development through the accomplishment of the following objectives: (1) To apply pharmacology expertise to the ETCTN early drug development efforts by assisting in study design and other PK-related activities; (2) To analyze biological samples with quantitative assays; and (3) To perform non-compartmental, compartmental, and population PK analyses and report the results to study teams and CTEP in a timely manner. Our approach will be to use our technical and scientific expertise to lead all PK-related activities and integrate these PK investigations with the other clinical and correlative studies performed during the drug development process. We will develop, validate, and implement accurate, precise, and sensitive assays for study drugs and metabolites in plasma, tissues and other biological samples, and analyze clinical samples from the ETCTN LOAs. Lastly, we will derive PK parameters to characterize the ADME of agents in ETCTN trials, integrate these results with pharmacodynamic measures of drug response and report to CTEP and the clinical team to optimally inform ongoing and future development of CTEP agents and their combinations.