A Phase I Study of DX-8951f (Exatecan Mesylate for Injection) in Patients With Renal Dysfunction
- Determine the maximum tolerated dose of exatecan mesylate in patients with advanced
solid tumors and varying degrees of renal dysfunction.
- Determine the dose-limiting and non-dose-limiting toxic effects of this drug in these
- Determine the effects of renal dysfunction on the plasma pharmacokinetics and
pharmacodynamics of this drug in these patients.
- Establish a model for dosing this drug in patients with impaired renal function.
OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to
severity of renal dysfunction (normal vs mild vs moderate vs severe).
Patients receive exatecan mesylate IV over 30 minutes on days 1-5. Courses repeat every 3
weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients in each renal dysfunction stratum receive escalating doses of
exatecan mesylate until the maximum tolerated dose (MTD) is determined. The MTD is defined
as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting
toxicity. Patients in the normal renal function stratum do not undergo dose escalation.
Patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 45 patients (6 normal, 9 mild, 12 moderate, and 18 severe
renal dysfunction) will be accrued for this study within 1.5 years.
Primary Purpose: Treatment
Carolyn Britten, MD
Jonsson Comprehensive Cancer Center
United States: Federal Government
|Jonsson Comprehensive Cancer Center, UCLA||Los Angeles, California 90095-1781|
|Brooke Army Medical Center||Fort Sam Houston, Texas 78234-6200|
|Veterans Affairs Medical Center - San Antonio (Murphy)||San Antonio, Texas 78284|
|Cancer Therapy and Research Center||San Antonio, Texas 78229|
|St. Luke's Lutheran Hospital||San Antonio, Texas 78229|