Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

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.

Further Study Information

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 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.

Eligibility 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

• Measurable or evaluable disease (patients with reliable tumor markers are allowed)

• No symptomatic CNS metastases

• Brain metastases previously treated with radiotherapy and/or surgery and stable for at least 8 weeks are eligible

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count at least 1,000/mm^3

• Platelet count at least 50,000/mm^3

Hepatic

• Bilirubin 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)

Renal

• Abnormal kidney function allowed

• No dialysis within 4 hours of study drug

Cardiovascular

• No symptomatic congestive heart failure

• No unstable angina pectoris

• No cardiac arrhythmia

• No New York Heart Association class III or IV heart disease

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective barrier contraception during and for 30 days after study participation

• No preexisting neuropathy grade 2 or greater

• No psychiatric illness or social situation that would preclude study compliance

• No ongoing or active infection

• No other concurrent uncontrolled illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 4 weeks since prior immunotherapy

• More than 4 weeks since prior biologic therapy

• No concurrent immunotherapy

• No concurrent thalidomide

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered

• No concurrent chemotherapy

Endocrine therapy

• Concurrent steroids for CNS metastases allowed provided dose is stable

Radiotherapy

• See 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

Surgery

• See Disease Characteristics

Other

• No 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

Trial Contact Information

Trial Lead Organizations/Sponsors

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Daniel Mulkerin

Study Chair

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00054483
Information obtained from ClinicalTrials.gov on December 14, 2011

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