Bortezomib in Treating Patients With Advanced Cancer and Kidney Dysfunction

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00054483
First received: February 5, 2003
Last updated: May 15, 2013
Last verified: May 2013
  Purpose

Phase I trial to study the effectiveness of bortezomib in treating patients who have advanced cancer and kidney dysfunction. Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth.


Condition Intervention Phase
Adult Grade III Lymphomatoid Granulomatosis
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Nodal Marginal Zone B-cell Lymphoma
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Grade III Lymphomatoid Granulomatosis
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Small Lymphocytic Lymphoma
Refractory Multiple Myeloma
Splenic Marginal Zone Lymphoma
Stage III Multiple Myeloma
Stage IV Adult Burkitt Lymphoma
Stage IV Adult Diffuse Large Cell Lymphoma
Stage IV Adult Diffuse Mixed Cell Lymphoma
Stage IV Adult Diffuse Small Cleaved Cell Lymphoma
Stage IV Adult Immunoblastic Large Cell Lymphoma
Stage IV Adult Lymphoblastic Lymphoma
Stage IV Grade 1 Follicular Lymphoma
Stage IV Grade 2 Follicular Lymphoma
Stage IV Grade 3 Follicular Lymphoma
Stage IV Mantle Cell Lymphoma
Stage IV Marginal Zone Lymphoma
Stage IV Small Lymphocytic Lymphoma
Unspecified Adult Solid Tumor, Protocol Specific
Waldenström Macroglobulinemia
Drug: bortezomib
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
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 in terms of 20S proteasome activity following bortezomib administration [ Time Frame: Days 1 and 8 pre-infusion (of course 1) and 5, 15, 30, and 60 minutes, and 2, 4, 6, 8, 12, and 24 hours post-bortezomib administration ] [ Designated as safety issue: No ]
  • Dose-limiting toxicities of bortezomib graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 [ Time Frame: Up to 21 days ] [ Designated as safety issue: Yes ]

Enrollment: 69
Study Start Date: January 2003
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (bortezomib)
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.
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologic proof of malignancy (including non-Hodgkin's lymphoma and multiple myeloma)
  • Patients must have measurable or evaluable disease; patients with reliable tumor markers (as determined by protocol chairman) are eligible for participation
  • ANC >= 1000/uL
  • PLT >= 50,000/uL
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • AST =< 2.5 x ULN or AST =< 5 x ULN if liver involvement
  • Patients with abnormal kidney function will be allowed and will be grouped accordingly
  • Willingness to return to treating institution for follow-up
  • Life expectancy >= 12 weeks
  • Willingness to provide all biologic specimens as required by the protocol

Exclusion Criteria:

  • Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
  • ECOG performance status (PS) 3 or 4
  • Uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Any of the following prior therapies:

    • Chemotherapy ≤ 4 weeks
    • Mitomycin C/nitrosoureas ≤ 6 weeks
    • Immunotherapy ≤ 4 weeks
    • Biologic therapy ≤ 4 weeks
    • Radiation therapy ≤ 2 weeks
    • Radiation to > 50 % of bone marrow (excepting patients who have had total body irradiation incorporated into bone marrow or stem cell transplantation; all other eligibility criteria still apply)
    • PS-341 treatment
  • Failure to fully recover from effects of prior chemotherapy regardless of interval since last treatment (excludes renal function)
  • New York Heart Association classification III or IV
  • Symptomatic CNS metastases; patients who have received definitive treatment for brain metastases (radiation and/or surgery) and are stable for >= 8 weeks are eligible; eligible patients with brain metastases should not be taking enzyme-inducing anticonvulsants and should be receiving stable doses of steroids
  • Any of the following:

    • Pregnant women
    • Nursing women
    • Men or women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], or abstinence, etc.)
    • This study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown
  • Other concurrent chemotherapy, immunotherapy, or radiotherapy
  • HIV-positive patients receiving anti-retroviral therapy (HAART); there is a potential for pharmacokinetic interactions
  • Concurrent use of other investigational agent (including thalidomide); bisphosphonate therapy (e.g. pamidronate or zoledronate) will not be considered investigational agents for the purpose of trial eligibility
  • Pre-existing grade >= 2 neuropathy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00054483

Locations
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Investigators
Principal Investigator: Daniel Mulkerin University of Wisconsin Hospital and Clinics
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00054483     History of Changes
Other Study ID Numbers: NCI-2012-02917, CO 02903, CDR0000270687, U01CA062491, U01CA069852, U01CA062505, U01CA062487, U01CA069853, U01CA062502, U01CA099168
Study First Received: February 5, 2003
Last Updated: May 15, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Burkitt Lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma
Lymphoma, B-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Extranodal NK-T-Cell
Lymphoma, Follicular
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Immunoblastic
Lymphoma, Mantle-Cell
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell
Lymphomatoid Granulomatosis
Multiple Myeloma
Neoplasms, Plasma Cell
Waldenstrom Macroglobulinemia
Blood Protein Disorders
Cardiovascular Diseases
DNA Virus Infections
Epstein-Barr Virus Infections
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Herpesviridae Infections
Immune System Diseases
Immunoproliferative Disorders
Leukemia
Leukemia, B-Cell
Leukemia, Lymphoid
Lymphatic Diseases

ClinicalTrials.gov processed this record on October 22, 2014