This competing renewal proposes to define the recommended phase II dose and toxicities of new antineoplastic agents, including approaches to amelioration of such toxicity; to define the pharmacokinetics, pharmacodynamics, and pharmacogenetics of new antineoplastic agents; to develop new combinations that enhance the therapeutic index and/or oral bioavailability of new or established agents; and to develop and implement novel methodological approaches to phase I studies. This proposal includes three ongoing studies and five new studies. The proposed new studies build on the applicants' experience and accomplishments with irinotecan and O6-benzylguanine. In addition, three new studies are proposed involving tyrosine kinase inhibitors (e.g. 0SI-774, imatinib). Most of the studies will evaluate novel therapies in patients with advanced solid tumors. In addition, one ongoing and one planned study focus on patients with advanced hematologic malignancies. All of the proposed studies will include pharmacokinetic or correlative components. The latter will include pharmacodynamic studies of tumor and normal tissue evaluating signal transduction endpoints, as well as pharmacogenetic studies. The proposed pharmacogenetic studies will be performed in collaboration with the Pharmacogenetics of Anticancer Agents Research (PAAR) Group, chaired by the Principal Investigator. The PAAR Group is part of a larger NIH Pharmacogenetics Research Network, administered through NIGMS. This application also includes a proposal for the creation of an Early Clinical Trials Network to facilitate inter-institutional collaborations involving NCI-sponsored early clinical trials.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01CA069852-13
Application #
7201657
Study Section
Special Emphasis Panel (ZCA1-SRRB-E (O1))
Program Officer
Ivy, S Percy
Project Start
1995-05-10
Project End
2008-02-29
Budget Start
2007-03-01
Budget End
2008-02-29
Support Year
13
Fiscal Year
2007
Total Cost
$624,589
Indirect Cost
Name
University of Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
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