Bortezomib in Treating Patients With Advanced Cancer and Kidney Dysfunction

PRIMARY OBJECTIVES: 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 this study.