PITT-CAL ETCTN PK Resource Laboratory

总结 本U24合作协议的目的是支持由两个国家癌症研究所组成的联盟， （NCI）-指定的综合癌症中心资助的药代动力学（PK）核心实验室，已加入 作为NCI实验治疗-临床试验的统一、集成PK资源 网络（ETCTN）。UPMC希尔曼癌症中心（HCC）癌症药代动力学和 药效学机构和City of Hope（COH）分析药理学核心机构在全国范围内 因其在抗癌药物药理学表征方面的领导地位而受到认可。新成立的 PITT-CAL ETCTN PK资源实验室（PITT-CAL）建议系统评价ADME特征 通过完成以下工作，在临床开发的各个阶段使用CTEP药物 目的：（1）通过协助ETCTN早期药物开发工作， 研究设计和其他PK相关活动;（2）通过定量分析分析生物样品;以及 (3)进行非房室、房室和群体PK分析，并将结果报告给研究 团队和CTEP及时。我们的方法将是利用我们的技术和科学专长， 所有PK相关活动，并将这些PK研究与其他临床和相关研究整合 在药物开发过程中。我们将开发，验证和实施准确，精确， 以及血浆、组织和其他生物样本中研究药物和代谢物的灵敏度测定，以及 分析来自ETCTN LOA的临床样本。最后，我们将推导出PK参数，以表征 ETCTN试验中药物的ADME，将这些结果与药物反应的药效学指标相结合 并向CTEP和临床团队报告，以最佳方式告知CTEP药物的持续和未来发展 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.