The University of Chicago Medicine (UC) proposes to join the Early Therapeutics-Clinical Trials Network (ET-CTN). The early development of novel anticancer agents requires innovative approaches to adapt to the changing environment of cancer therapeutics development. Standards of care for advanced metastatic solid tumors have improved, rapid technological advances in molecular biotechnology have brought new tools and therapeutic strategies, and advances in information technology enable collection and analysis of larger datasets and more efficient inter-institutional collaboration. But fundamental principles of drug development remain essential to improving cancer care. Our center proposes to join the ET-CTN as a highly collaborative site, experienced in team science, with specific expertise in: innovative clinical trial design and quantitative analysis methods, application and validation of biomarkers in early therapeutics development, and pharmacogenomics of cancer therapeutics. Our site brings the resources and expertise of our Comprehensive Cancer Center, an early therapeutics development team with extensive experience, and a team of clinical oncologists with both disease-specific patient care and research expertise. Our leadership have already conducted effective team science within the NCI Investigational Drug Steering Committee and Cooperative Groups as well as in the NIGMS-sponsored Pharmacogenomics Research Network. UC team members will participate actively on projects led by the collaborative groups in the network, offering their relevant expertise. UC will lead efforts in pharmacogenomics, biomarker validation, and design and conduct of novel clinical trials. We also plan to implement computational modeling and simulation strategies to: 1) improve trial designs, 2) identify the range of doses of new agents to be tested in later trials, 3) to demonstrate relevance of candidate biomarkers for further development, and 4) support strategic decision-making by the ET-CTN on which agents and combinations are most likely to have the intended impact on clinical care in later phases of drug development.

Public Health Relevance

This grant will support the joint efforts of a team of medical oncologists, pharmacologists, nurses, pathologists, and laboratory scientists from the University of Chicago who will work with a national network of similar researchers to conduct the early phase testing of new experimental anticancer drugs. This highly interactive team will help the National Cancer Institute to expedite the delivery of safer, more effective treatments to cancer patients.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project with Complex Structure Cooperative Agreement (UM1)
Project #
5UM1CA186705-02
Application #
8827737
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Ivy, S Percy
Project Start
2014-03-26
Project End
2017-02-28
Budget Start
2015-03-01
Budget End
2017-02-28
Support Year
2
Fiscal Year
2015
Total Cost
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
Alachkar, H; Fulton, N; Sanford, B et al. (2017) Expression and polymorphism (rs4880) of mitochondrial superoxide dismutase (SOD2) and asparaginase induced hepatotoxicity in adult patients with acute lymphoblastic leukemia. Pharmacogenomics J 17:274-279
Sharma, Manish R; Ratain, Mark J (2016) Taking a Measured Approach to Toxicity Data in Phase I Oncology Clinical Trials. Clin Cancer Res 22:527-9
Rudek, Michelle A; Graham, Richard A; Ratain, Mark J (2016) Harmonization of Renal Function Assessment Is Needed During Early Clinical Development of Oncology Drugs. J Clin Oncol 34:103-4
Geeleher, Paul; Loboda, Andrey; Lenkala, Divya et al. (2015) Predicting Response to Histone Deacetylase Inhibitors Using High-Throughput Genomics. J Natl Cancer Inst 107:
Alachkar, Houda; Mutonga, Martin; Malnassy, Gregory et al. (2015) T-LAK cell-originated protein kinase presents a novel therapeutic target in FLT3-ITD mutated acute myeloid leukemia. Oncotarget 6:33410-25
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
Mutonga, Martin; Tamura, Kenji; Malnassy, Gregory et al. (2015) Targeting Suppressor of Variegation 3-9 Homologue 2 (SUV39H2) in Acute Lymphoblastic Leukemia (ALL). Transl Oncol 8:368-75
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

Showing the most recent 10 out of 12 publications