Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Bortezomib in Treating Patients With Advanced Cancer and Kidney Dysfunction

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Closed	18 and over	NCI	WCCC-CO-02903 NCI-5874, CWRU-1Y03, CWRU-040315, 5874, NCT00054483

Objectives

1. Determine the pharmacokinetics and pharmacodynamics of bortezomib in patients with advanced malignancies and renal insufficiency.
2. Determine the safety and tolerability of this drug in these patients.
3. Determine the maximum tolerated dose of this drug in these patients.

Entry 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

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

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/mm³
• Platelet count at least 50,000/mm³

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

Expected Enrollment

A total of 60-69 patients (at least 12 per stratum) will be accrued for this study.

Outcomes

Pharmacokinetics and pharmacodynamics
Safety and tolerability
Maximum tolerated dose

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.

Trial Contact Information

Trial Lead Organizations

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Daniel Mulkerin, MD, Protocol chair		Ph: 608-262-9653; 800-622-8922

Registry Information
Official Title		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
Trial Start Date		2003-01-15
Trial Completion Date		2004-01-06 (estimated)
Registered in ClinicalTrials.gov		NCT00054483
Date Submitted to PDQ		2003-01-03
Information Last Verified		2007-07-06
NCI Grant/Contract Number		CA62491, CA14520, CA43703

Back to Top