A Phase I Pharmacokinetic Study of PS-341 in Patients With Advanced Malignancies and Varying Degrees of Liver Dysfunction for the CTEP-Sponsored Organ Dysfunction Working Group.
I. Determine the maximum tolerated dose of bortezomib in patients with advanced malignancies
and varying degrees of liver dysfunction.
II. Determine the safety and tolerability of this drug in these patients. III. Determine the
pharmacokinetics and pharmacodynamics of this drug in these patients with mild, moderate, or
severe liver insufficiency.
IV. Examine the dietary influences on bortezomib disposition and efficacy. V. Examine the
influences of proteasome inhibition on CYP 450 activity.
OUTLINE: This is a multicenter, dose-escalation study. Patients are stratified according to
hepatic function (normal vs mild dysfunction vs moderate dysfunction vs severe dysfunction).
Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11.
Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients per stratum receive escalating doses of bortezomib until the maximum
tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2
of 6 patients experience dose-limiting toxicity.
[Note: Patients with normal hepatic function do not receive escalating doses of bortezomib.]
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Wayne State University
United States: Food and Drug Administration
|Johns Hopkins University||Baltimore, Maryland 21205|
|City of Hope Medical Center||Duarte, California 91010|
|Wayne State University||Detroit, Michigan 48202|