) One major goal of a phase I trial is identification of the optimal clinical dose, route and schedule to be used in subsequent phase II studies which will quantitate clinical efficacy against specific human cancers. Phase I clinical trials are the culmination of the costly and laborious preclinical screening process and are the foundation for studies of human antitumor activity. The University of Wisconsin has had continuous NCI funding for its phase I studies since 1979. From 1994 to 1996 our NCI grant accrual totaled 261 with 100 patients entered on trial during 1996. We currently have eleven open trials. This proposal details our extensive experience in conducting phase I trials and outlines our goals for continuation of such work as detailed in our specific aims:
Aim 1 : Determination of the Maximum Tolerable Dose and Dose Limiting Toxicities of Novel Anticancer Agents.
Aim 2 : Use of Laboratory and Clinical Correlates to Improve Understanding of Mechanisms of Drug Action.
Aim 3 : Integration of Pharmacokinetics/Pharmacodynamic Studies in Phase I Trials.
Aim 4 : Development of Novel Phase I Study Designs.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project--Cooperative Agreements (U01)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-RLB-7 (O1))
Program Officer
Jensen, Leeann T
Project Start
Project End
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Budget End
Support Year
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University of Wisconsin Madison
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Kyriakopoulos, Christos E; Braden, Amy M; Kolesar, Jill M et al. (2017) A phase I study of tivantinib in combination with temsirolimus in patients with advanced solid tumors. Invest New Drugs 35:290-297
Rampurwala, Murtuza; Wisinski, Kari B; Burkard, Mark E et al. (2017) Phase 1b study of orteronel in postmenopausal women with hormone-receptor positive (HR+) metastatic breast cancer. Invest New Drugs 35:87-94
Pili, Roberto; Liu, Glenn; Chintala, Sreenivasulu et al. (2017) Combination of the histone deacetylase inhibitor vorinostat with bevacizumab in patients with clear-cell renal cell carcinoma: a multicentre, single-arm phase I/II clinical trial. Br J Cancer 116:874-883
Wisinski, Kari B; Tevaarwerk, Amye J; Burkard, Mark E et al. (2016) Phase I Study of an AKT Inhibitor (MK-2206) Combined with Lapatinib in Adult Solid Tumors Followed by Dose Expansion in Advanced HER2+ Breast Cancer. Clin Cancer Res 22:2659-67
Deming, Dustin A; Cavalcante, Ludmila L; Lubner, Sam J et al. (2016) A phase I study of selumetinib (AZD6244/ARRY-142866), a MEK1/2 inhibitor, in combination with cetuximab in refractory solid tumors and KRAS mutant colorectal cancer. Invest New Drugs 34:168-75
Wisinski, Kari B; Cantu, Colby A; Eickhoff, Jens et al. (2015) Potential cytochrome P-450 drug-drug interactions in adults with metastatic solid tumors and effect on eligibility for Phase I clinical trials. Am J Health Syst Pharm 72:958-65
LoConte, Noelle K; Razak, Albiruni R A; Ivy, Percy et al. (2015) A multicenter phase 1 study of ? -secretase inhibitor RO4929097 in combination with capecitabine in refractory solid tumors. Invest New Drugs 33:169-76
Deming, Dustin A; Ninan, Jacob; Bailey, Howard H et al. (2014) A Phase I study of intermittently dosed vorinostat in combination with bortezomib in patients with advanced solid tumors. Invest New Drugs 32:323-9
Schelman, William R; Mohammed, Tabraiz A; Traynor, Anne M et al. (2014) A phase I study of AT-101 with cisplatin and etoposide in patients with advanced solid tumors with an expanded cohort in extensive-stage small cell lung cancer. Invest New Drugs 32:295-302
Bruce, Justine Yang; Kolesar, Jill M; Hammers, Hans et al. (2014) A phase I pharmacodynamic trial of sequential sunitinib with bevacizumab in patients with renal cell carcinoma and other advanced solid malignancies. Cancer Chemother Pharmacol 73:485-93

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