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.
This PITT-CAL ETCTN PK Resource Laboratory will serve as a consolidated, integrated resource providing PK analyses to the NCI Experimental Therapeutics Clinical Trials Network (ETCTN). By characterizating absorption, disposition, metabolism, and excretion (ADME), and integration of this knowledge with biomarker and clinical findings through application of our pharmacology expertise, we will rapidly and efficiently advance CTEP agents through the various phases of clinical development, ultimately enhancing the quality of care of cancer patients.
