During FY17, the Blood Processing Core (BPC) provided support to over 90 clinical trials. This support ranged from sample pickup and processing, to full analytical method development and validation, pharmacokinetic and pharmacogenetic analysis and assistance with trial design. In FY17, the CPP processed over 28,000 biological samples including blood, urine, cerebrospinal fluid, pleural effusion aspirate, saliva, bone marrow aspirate, and ascites. Upon arrival, all samples are processed according to the clinical protocol (per standard operating procedures), entered into a database for sample handling and storage purposes and cataloged into a software system. The BPC provides a broad range of services including the development and validation of procedures for specimen processing, analyses, and DNA extraction to establish protocols that optimize specimen integrity and consistency. The first priority in characterizing the pharmacokinetics of an anticancer agent is to develop a reliable and reproducible analytical method for quantitating agents in biological fluids and tissues. The Clinical Pharmacology Program (CPP) utilizes high performance liquid chromatography (HPLC) coupled with state-of-the-art detection instruments including mass spectrometers, tandem mass spectrometers (MS/MS), diode array detectors (for UV absorption), and fluorescence detection to measure drug concentrations. Following method development, assays are validated according to the FDA Guidelines for Bioanalytical Method Development. Over the years, the CPP has developed analytical methods for a wide range of therapeutics, numerous which have been published, including depsipeptide, TNP-470, phenylacetate, phenylbutyrate, tamoxifen, UCN-01, CAI, thalidomide, COL-3, suramin, melphalan, erlotinib, perifosine, SU5416, 2ME, MS-275, ketoconazole, lenalidomide, romidepsin, AZD2281 and gemicitabine, sorafenib, finasteride, nelfinavir, 17-DMAG, clopidogrel and and its MPB-derivatized active thiol-metabolite (CAMD), Hsp90 inhibitor PF-04928473, irinotecan (its active metabolite SN38, and glucuronidated SN38), Trk kinase inhibitor AZD7451, pomalidomide, olaparib, sorafenib, belinostat, cediranib, abiraterone, cabozantinib, carfilzomib, midazolam, lapatinib, temozolomide, perifosine, and valproic acid. We have recently developed a sensitive and selective ultra-high performance liquid chromatography-tandem mass spectrometric (UHPLC-MS/MS ) method for the quantification of temozolomide in nonhuman primate (NHP) plasma, cerebrospinal fluid (CSF), and brain extracellular fluid (ECF) following microdialysis.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Scientific Cores Intramural Research (ZIC)
Project #
1ZICSC006536-24
Application #
9556863
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
24
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Clinical Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Jackson, Sadhana; Weingart, Jon; Nduom, Edjah K et al. (2018) The effect of an adenosine A2A agonist on intra-tumoral concentrations of temozolomide in patients with recurrent glioblastoma. Fluids Barriers CNS 15:2
Manasanch, Elisabet E; de Larrea, Carlos Fernández; Zingone, Adriana et al. (2017) Enzymatic activities of circulating plasma proteasomes in newly diagnosed multiple myeloma patients treated with carfilzomib, lenalidomide and dexamethasone. Leuk Lymphoma 58:639-645
Ferraz Nogueira Filho, Marco A; Peer, Cody J; Nguyen, Jeffers et al. (2017) A simple and rapid UHPLC-MS/MS method for the quantitation of the dual aurora kinase A/B inhibitor SCH-1473759 in murine plasma. J Pharm Biomed Anal 132:223-226
Lee, Jung-Min; Cimino-Mathews, Ashley; Peer, Cody J et al. (2017) Safety and Clinical Activity of the Programmed Death-Ligand 1 Inhibitor Durvalumab in Combination With Poly (ADP-Ribose) Polymerase Inhibitor Olaparib or Vascular Endothelial Growth Factor Receptor 1-3 Inhibitor Cediranib in Women's Cancers: A Dose-Escala J Clin Oncol 35:2193-2202
Uldrick, Thomas S; Gonçalves, Priscila H; Wyvill, Kathleen M et al. (2017) A Phase Ib Study of Sorafenib (BAY 43-9006) in Patients with Kaposi Sarcoma. Oncologist 22:505-e49
Lee, Jung-Min; Peer, Cody J; Yu, Minshu et al. (2017) Sequence-Specific Pharmacokinetic and Pharmacodynamic Phase I/Ib Study of Olaparib Tablets and Carboplatin in Women's Cancer. Clin Cancer Res 23:1397-1406
Lee, Jung-Min; Hays, John L; Chiou, Victoria L et al. (2017) Phase I/Ib study of olaparib and carboplatin in women with triple negative breast cancer. Oncotarget 8:79175-79187
Dao, Kim; Chtioui, Haithem; Lu, Yimin et al. (2017) Pharmacokinetics of Pomalidomide in a Patient Receiving Hemodialysis Using a High-Cutoff Filter. Am J Kidney Dis 69:553-554
Dao, Kim; Lu, Yimin; Peer, Cody J et al. (2017) Pharmacokinetics of lenalidomide during high cut-off dialysis in a patient with multiple myeloma and renal failure. Cancer Chemother Pharmacol 79:215-218
Goey, Andrew K L; Sissung, Tristan M; Peer, Cody J et al. (2016) Effects of UGT1A1 genotype on the pharmacokinetics, pharmacodynamics, and toxicities of belinostat administered by 48-hour continuous infusion in patients with cancer. J Clin Pharmacol 56:461-73

Showing the most recent 10 out of 43 publications