Bortezomib in Treating Patients With Advanced Cancer and Kidney Dysfunction

May 15, 2013 updated by: National Cancer Institute (NCI)

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

69

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Hospital and Clinics

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Names:
  • pharmacological studies
Drug: bortezomib
Given IV
Other Names:
  • MLN341
  • LDP 341
  • VELCADE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
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
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
Up to 21 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Daniel Mulkerin, University of Wisconsin, Madison

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2003

Primary Completion (Actual)

September 1, 2009

Study Registration Dates

First Submitted

February 5, 2003

First Submitted That Met QC Criteria

February 5, 2003

First Posted (Estimate)

February 6, 2003

Study Record Updates

Last Update Posted (Estimate)

May 16, 2013

Last Update Submitted That Met QC Criteria

May 15, 2013

Last Verified

May 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-02917
  • U01CA099168 (U.S. NIH Grant/Contract)
  • U01CA062502 (U.S. NIH Grant/Contract)
  • U01CA062505 (U.S. NIH Grant/Contract)
  • U01CA069852 (U.S. NIH Grant/Contract)
  • U01CA062491 (U.S. NIH Grant/Contract)
  • U01CA062487 (U.S. NIH Grant/Contract)
  • U01CA069853 (U.S. NIH Grant/Contract)
  • CO 02903
  • CDR0000270687

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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