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Bortezomib in Treating Patients With Advanced Cancer and Kidney Dysfunction
The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2007 by National Cancer Institute (NCI).   Recruitment status was  Active, not recruiting

First Received on February 5, 2003.   Last Updated on November 16, 2008   History of Changes
Sponsor: University of Wisconsin, Madison
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00054483
  Purpose

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 Intervention Phase
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Unspecified Adult Solid Tumor, Protocol Specific
Drug: bortezomib
Phase I

Study Type: Interventional
Study Design: Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Pharmacokinetics and pharmacodynamics [ Designated as safety issue: No ]
  • Safety and tolerability [ Designated as safety issue: Yes ]
  • Maximum tolerated dose [ Designated as safety issue: Yes ]

Estimated Enrollment: 69
Study Start Date: January 2003
Estimated Primary Completion Date: January 2004 (Final data collection date for primary outcome measure)
Detailed Description:

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00054483

Locations
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States, 90089-9181
City of Hope Medical Group
Pasadena, California, United States, 91105
University of California Davis Cancer Center
Sacramento, California, United States, 95817
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
United States, New York
Albert Einstein Cancer Center at Albert Einstein College of Medicine
Bronx, New York, United States, 10461
NYU Cancer Institute at New York University Medical Center
New York, New York, United States, 10016
United States, Ohio
Ireland Cancer Center at University Hospitals/Case Medical Center
Cleveland, Ohio, United States, 44106-5065
United States, Pennsylvania
UPMC Cancer Centers
Pittsburgh, Pennsylvania, United States, 15232
United States, Texas
Institute for Drug Development
San Antonio, Texas, United States, 78245-3217
United States, Wisconsin
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792-6164
Australia, New South Wales
Sydney Cancer Centre at Royal Prince Alfred Hospital
Sydney, New South Wales, Australia, 2050
Sponsors and Collaborators
University of Wisconsin, Madison
Investigators
Study Chair: Daniel Mulkerin, MD University of Wisconsin, Madison
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00054483     History of Changes
Other Study ID Numbers: CDR0000270687, WCCC-CO-02903, NCI-5874, CWRU-1Y03, CWRU-040315
Study First Received: February 5, 2003
Last Updated: November 16, 2008
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
unspecified adult solid tumor, protocol specific
stage III multiple myeloma
recurrent grade 1 follicular lymphoma
stage IV grade 1 follicular lymphoma
recurrent grade 3 follicular lymphoma
stage IV grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma
recurrent grade 2 follicular lymphoma
stage IV grade 2 follicular lymphoma
recurrent adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
stage IV adult lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
stage IV adult Burkitt lymphoma
recurrent mantle cell lymphoma
stage IV mantle cell lymphoma
refractory multiple myeloma
recurrent adult diffuse mixed cell lymphoma
stage IV adult diffuse mixed cell lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
stage IV small lymphocytic lymphoma
stage IV marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma

Additional relevant MeSH terms:
Neoplasms
Lymphoma
Lymphoma, Non-Hodgkin
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Lymphoma, Large-Cell, Immunoblastic
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Bortezomib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 12, 2012