A Phase I Pharmacokinetic Study of PS341 in Patients With Advanced Malignancies and Varying Degrees of Renal Dysfunction for the CTEP-Sponsored Organ Dysfunction Working Group
I. To identify the pharmacokinetic and pharmacodynamic profile of PS-341 in patients with
advanced malignancy and mild, moderate or severe renal insufficiency.
II. Evaluate the safety, tolerability, and the maximum tolerated dose of PS-341 for patients
with varying degrees of renal insufficiency.
OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to
most recent creatinine clearance (greater than 60 mL/min vs 40-59 mL/min vs 20-39 mL/min vs
less than 20 mL/min vs any creatinine clearance and undergoing renal dialysis).
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 receive escalating doses of bortezomib until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2
of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional
cohort of up to 12 patients is treated at the MTD.
PROJECTED ACCRUAL: A total of 60-69 patients (at least 12 per stratum) will be accrued for
Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science
Pharmacokinetics in terms of 20S proteasome activity following bortezomib administration
Days 1 and 8 pre-infusion (of course 1) and 5, 15, 30, and 60 minutes, and 2, 4, 6, 8, 12, and 24 hours post-bortezomib administration
University of Wisconsin Hospital and Clinics
United States: Food and Drug Administration
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