RATIONALE: Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth.
RATIONALE: Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth.PURPOSE: Phase I trial to study the effectiveness of bortezomib in treating patients who have advanced cancer and kidney dysfunction.Condition: – adult non-Hodgkin’s lymphoma- adult solid tumor- Multiple Myeloma- refractory plasma cell neoplasm Study Type: InterventionalStudy Design: Treatment Official Title: Phase I Study of Bortezomib in Patients With Advanced Malignancies and Renal InsufficiencyFurther Study Details: OBJECTIVES:Determine the pharmacokinetics and pharmacodynamics of bortezomib in patients with advanced malignancies and renal insufficiency. Determine the safety and tolerability of this drug in these patients. Determine the maximum tolerated dose of this drug in these patients. 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 6 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. Eligibility Ages Eligible for Study: 18 Years and above, Genders Eligible for Study: Both Criteria DISEASE CHARACTERISTICS:Histologically confirmed malignancy (including non-Hodgkin’s lymphoma and multiple myeloma) for which there is no known potentially curative or definitely life-extending therapy No symptomatic CNS metastases Brain metastases previously treated with radiotherapy and/or surgery and stable for at least 8 weeks are eligible PATIENT CHARACTERISTICS: Age18 and over Performance statusECOG 0-2 Life expectancyAt least 12 weeks HematopoieticAbsolute neutrophil count at least 1,000/mm^3 Platelet count at least 50,000/mm^3 HepaticBilirubin no greater than 1.5 times upper limit of normal (ULN) AST no greater than 2.5 times ULN (5 times ULN if liver involvement present) RenalAbnormal kidney function allowed No dialysis within 4 hours of study drug CardiovascularNo symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia No New York Heart Association class III or IV heart disease OtherNot pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception during and for 30 days after study participation No other uncontrolled illness No psychiatric illness or social situation that would preclude study compliance No ongoing or active infection No preexisting neuropathy grade 2 or greater PRIOR CONCURRENT THERAPY: Biologic therapyMore than 4 weeks since prior immunotherapy More than 4 weeks since prior biologic therapy No concurrent immunotherapy No concurrent thalidomide ChemotherapyMore than 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered No concurrent chemotherapy Endocrine therapyConcurrent steroids for CNS metastases allowed provided dose is stable RadiotherapySee Disease Characteristics More than 2 weeks since prior radiotherapy No prior radiotherapy to more than 50% of the bone marrow Prior total body irradiation for bone marrow or stem cell transplantation allowed No concurrent radiotherapy SurgerySee Disease Characteristics OtherNo prior bortezomib No concurrent antiretroviral therapy for HIV-positive patients No concurrent enzyme-inducing anticonvulsants for patients with brain metastases No other concurrent investigational agents Bisphosphonates (e.g., pamidronate or zoledronate) not considered investigational No concurrent bisphosphonates on days 1, 4, 8, and 11 of course 1 Royal Prince Alfred Hospital, Sydney, Sydney, New South Wales, 2050, Australia; Recruiting, Anne Hamilton, MD University of Wisconsin Comprehensive Cancer Center National Cancer Institute (NCI)
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