Abstract

This is a Phase I study of LY231514 in combination with irinotecan therapy in patients with metastatic cancer. This dose finding study will provide a recommendation for the dosing of LY231514 and irinotecan in future studies. LY-231514 is a folate antimetabolite with the primary mechanism of action the inhibition of the enzyme thymidylate synthase (TS), a folate dependent enzyme which catalyzes the process necessary for DNA synthesis. It is highly cytoxic in vitro. Irinotecan hydrochloride is a semisynthetic derivative of the plant alkaloid camptothecin and is one of new class of cytotoxic agents which inhibit the enzyme topoisomerase I, necessary for maintaining the conformation and functionality of DNA. The overall goal of this study in combining these agents is to develop a safe combination regimen for evaluation in relevant tumors, determining the MTD, the quantative and qualitative toxicities, assessing plasma pharmacokinetics, and documenting the antitumor activity.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR001346-19
Application #
6308719
Study Section
Project Start
1999-12-01
Project End
2000-11-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
19
Fiscal Year
2000
Total Cost
$16,409
Indirect Cost

  Institution

Name
University of Texas Health Science Center San Antonio
Department
Type
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229

  Publications

Kawaguchi-Suzuki, Marina; Cusi, Kenneth; Bril, Fernando et al. (2018) A Genetic Score Associates With Pioglitazone Response in Patients With Non-alcoholic Steatohepatitis. Front Pharmacol 9:752
Hayden, Kathleen M; Baker, Laura D; Bray, George et al. (2018) Long-term impact of intensive lifestyle intervention on cognitive function assessed with the National Institutes of Health Toolbox: The Look AHEAD study. Alzheimers Dement (Amst) 10:41-48
Unick, Jessica L; Gaussoin, Sarah A; Hill, James O et al. (2017) Objectively Assessed Physical Activity and Weight Loss Maintenance among Individuals Enrolled in a Lifestyle Intervention. Obesity (Silver Spring) 25:1903-1909
Kawaguchi-Suzuki, M; Bril, F; Kalavalapalli, S et al. (2017) Concentration-dependent response to pioglitazone in nonalcoholic steatohepatitis. Aliment Pharmacol Ther 46:56-61
Johnson, Karen C; Bray, George A; Cheskin, Lawrence J et al. (2017) The Effect of Intentional Weight Loss on Fracture Risk in Persons With Diabetes: Results From the Look AHEAD Randomized Clinical Trial. J Bone Miner Res 32:2278-2287
Lorenzo, Carlos; Festa, Andreas; Hanley, Anthony J et al. (2017) Novel Protein Glycan-Derived Markers of Systemic Inflammation and C-Reactive Protein in Relation to Glycemia, Insulin Resistance, and Insulin Secretion. Diabetes Care 40:375-382
Beavers, Kristen M; Leng, Iris; Rapp, Stephen R et al. (2017) Effects of Longitudinal Glucose Exposure on Cognitive and Physical Function: Results from the Action for Health in Diabetes Movement and Memory Study. J Am Geriatr Soc 65:137-145
Chao, Ariana M; Wadden, Thomas A; Gorin, Amy A et al. (2017) Binge Eating and Weight Loss Outcomes in Individuals with Type 2 Diabetes: 4-Year Results from the Look AHEAD Study. Obesity (Silver Spring) 25:1830-1837
Pownall, Henry J; Schwartz, Anne V; Bray, George A et al. (2016) Changes in regional body composition over 8 years in a randomized lifestyle trial: The look AHEAD study. Obesity (Silver Spring) 24:1899-905
Wing, Rena R; Espeland, Mark A; Clark, Jeanne M et al. (2016) Association of Weight Loss Maintenance and Weight Regain on 4-Year Changes in CVD Risk Factors: the Action for Health in Diabetes (Look AHEAD) Clinical Trial. Diabetes Care 39:1345-55

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