A Phase I Pharmacokinetic Study of STI571 in Patients With Advanced Malignancies and Varying Levels of Liver Dysfunction
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose and dose-limiting toxicity of imatinib mesylate in
patients with advanced malignancies and varying degrees of liver dysfunction.
II. Determine the effects of hepatic dysfunction on the pharmacodynamics and
pharmacokinetics of this drug in these patients.
III. Determine the non-dose-limiting toxic effects of this drug in these patients.
IV. Determine the response rate of these patients treated with this drug. V. Correlate the
Childs-Pugh classification of hepatic dysfunction with observed toxic effects,
pharmacodynamics, and pharmacokinetics of this drug in these patients.
OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to
liver dysfunction (normal vs mild vs moderate vs severe).
Patients receive oral imatinib mesylate daily. Courses repeat every 4 weeks in the absence
of disease progression or unacceptable toxicity. Cohorts of 3-6 patients within each stratum
(except normal stratum) receive escalating doses of imatinib 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.
PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study within 1 year.
Interventional
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD defined based on the toxicities observed during the first cycle of treatment
4 weeks
Yes
Ramesh Ramanathan
Principal Investigator
University of Pittsburgh
United States: Food and Drug Administration
NCI-2012-02418
NCT00025415
August 2001
Name | Location |
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University of Pittsburgh | Pittsburgh, Pennsylvania 15261 |