A Phase I Pharmacokinetic Study of STI571 in Patients With Advanced Malignancies and Varying Levels of Liver Dysfunction
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.
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
University of Pittsburgh
United States: Food and Drug Administration
|University of Pittsburgh||Pittsburgh, Pennsylvania 15261|