Abstract

) The overall objective of this proposal is to conduct phase I and pharmacological studies of new anticancer agents. These studies will aim to define the recommended phase II dose, toxicities, pharmacokinetics, and pharmacodynamics of such agents. Some of these trials may incorporate pharmacokinetics or pharmacodynamic modulators. Five new s t udies are proposed. These include 1)evaluation of genotyping for abnormalities in the UGT*1.1 promoters region (known to cause Gilbert's syndrome) and phenotyping with buprenorphine (a known substrate for UGI*1.1) a s p o t e ntial predictors of CPT-11 toxicity (diarrhea) and SN-38 glucuronidation (known to be a substrate for UGT*1.1); 2) evaluation of [O]6-benzylguanine (BG) pharmacodynamics in patients with colorectal cancer or sarcoma undergoing surgical resections; 3)evaluation of BG in combination with temozolomide; 4)evaluation of ketoconazole (a potent inhibitor of CYP3A4 on carboxyanidoimadzole (a substrate for CYP3A4) pharmacokinetics and toxicity; and 5)evaluation of UCN-01 on biweekly (24 hr infusion) schedule. All studies will include both pharmacokinetics and correlative laboratory studies. The project total accrual is 375 patients, or 75 patients per year.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
2U01CA069852-04
Application #
2467965
Study Section
Special Emphasis Panel (ZCA1-RLB-7 (O1))
Program Officer
Grochow, Louise
Project Start
1995-05-10
Project End
2003-02-28
Budget Start
1998-05-01
Budget End
1999-02-28
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637

  Publications

Geeleher, Paul; Loboda, Andrey; Lenkala, Divya et al. (2015) Predicting Response to Histone Deacetylase Inhibitors Using High-Throughput Genomics. J Natl Cancer Inst 107:
Maitland, Michael L; Xu, Chun-Fang; Cheng, Yu-Ching et al. (2015) Identification of a variant in KDR associated with serum VEGFR2 and pharmacodynamics of Pazopanib. Clin Cancer Res 21:365-72
O'Donnell, Peter H; Karovic, Sanja; Karrison, Theodore G et al. (2015) Serum C-Telopeptide Collagen Crosslinks and Plasma Soluble VEGFR2 as Pharmacodynamic Biomarkers in a Trial of Sequentially Administered Sunitinib and Cilengitide. Clin Cancer Res 21:5092-9
Odenike, Olatoyosi; Halpern, Anna; Godley, Lucy A et al. (2015) A phase I and pharmacodynamic study of the histone deacetylase inhibitor belinostat plus azacitidine in advanced myeloid neoplasia. Invest New Drugs 33:371-9
Karovic, S; Wen, Y; Karrison, T G et al. (2014) Sorafenib dose escalation is not uniformly associated with blood pressure elevations in normotensive patients with advanced malignancies. Clin Pharmacol Ther 96:27-35
Paller, Channing J; Bradbury, Penelope A; Ivy, S Percy et al. (2014) Design of phase I combination trials: recommendations of the Clinical Trial Design Task Force of the NCI Investigational Drug Steering Committee. Clin Cancer Res 20:4210-7
Ramírez, Jacqueline; Kim, Tae Won; Liu, Wanqing et al. (2014) A pharmacogenetic study of aldehyde oxidase I in patients treated with XK469. Pharmacogenet Genomics 24:129-32
Abrams, Jeffrey S; Mooney, Margaret M; Zwiebel, James A et al. (2013) Implementation of timeline reforms speeds initiation of National Cancer Institute-sponsored trials. J Natl Cancer Inst 105:954-9
Sharma, Manish R; Karrison, Theodore G; Kell, Bethany et al. (2013) Evaluation of food effect on pharmacokinetics of vismodegib in advanced solid tumor patients. Clin Cancer Res 19:3059-67
O'Donnell, Peter H; Undevia, Samir D; Stadler, Walter M et al. (2012) A phase I study of continuous infusion cilengitide in patients with solid tumors. Invest New Drugs 30:604-10

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