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CompletedNCT00091117Updated Dec 16, 2013

Bortezomib in Treating Patients With Advanced Cancer and Liver Dysfunction

A Phase 1 interventional study of bortezomib and pharmacological study in Hepatic Complications and Malignant Neoplasm, sponsored by National Cancer Institute (NCI). Completed at 3 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2013-12-16.

Sponsored by National Cancer Institute (NCI) · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
80
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. This phase I trial is studying the side effects and best dose of bortezomib in treating patients with advanced cancer and liver dysfunction.

Read the detailed description

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of bortezomib in patients with advanced malignancies and varying degrees of liver dysfunction.

II. Determine the safety and tolerability of this drug in these patients. III. Determine the pharmacokinetics and pharmacodynamics of this drug in these patients with mild, moderate, or severe liver insufficiency.

IV. Examine the dietary influences on bortezomib disposition and efficacy. V. Examine the influences of proteasome inhibition on CYP 450 activity.

OUTLINE: This is a multicenter, dose-escalation study. Patients are stratified according to hepatic function (normal vs mild dysfunction vs moderate dysfunction vs severe dysfunction).

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 per stratum receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

[Note: Patients with normal hepatic function do not receive escalating doses of bortezomib.]

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Conditions studied

  • Hepatic Complications
  • Malignant Neoplasm
03

In context

Neoplasms

9,365 studies on the registry are indexed under Neoplasms; 2,489 are open to participants now.

This study's enrollment of 80 is above the median of 50 across 7,253 interventional studies indexed under Neoplasms.

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Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Inclusion Criteria:

  • Histologically confirmed malignancy for which no known standard therapy that is potentially curative or definitely capable of extending life expectancy exists
  • Tumor types may include any of the following: solid tumors:

    • Non-Hodgkin's lymphoma
    • Hepatocellular carcinoma, as evidenced by liver mass, elevated alpha-fetoprotein level (>= 500 ng/mL), and positive serology for hepatitis
  • Pathological confirmation is not required
  • Confirmatory evidence for a prior Hepatitis B infection (HBsAg, HBcAb and/or HBsAb) required
  • No symptomatic CNS metastases
  • Brain metastasis allowed if the following criteria are met:

    • Received prior definitive treatment (radiation and/or surgery
    • Stable disease for >= 4 weeks
    • Not currently on enzyme-inducing anticonvulsants and steroids
  • Life expectancy of at least 12 weeks
  • Absolute neutrophil count >= 1,000/mm\^3
  • Platelet count >= 100,000/mm\^3
  • Biliary obstruction for which a shunt has been placed allowed provided the shunt has been in place for >= 10 days AND liver function is stable, defined as 2 measurements taken >= 2 days apart that qualify the patient for the same hepatic dysfunction stratum
  • No biliary sepsis
  • Creatinine =\< 1.5 mg/dL
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • No New York Heart Association class III or IV heart disease
  • Not pregnant or nursing
  • Negative pregnancy test
  • No preexisting neuropathy >= grade 2
  • No ongoing or active infection
  • No other concurrent uncontrolled illness that would preclude study participation
  • No psychiatric illness or social situation that would preclude study compliance
  • More than 4 weeks since prior immunotherapy
  • More than 4 weeks since prior biologic therapy
  • No concurrent prophylactic colony-stimulating factors
  • No concurrent immunotherapy
  • No concurrent thalidomide
  • Concurrent epoetin alfa or darbepoetin alfa for management of cancer-associated anemia allowed
  • Recovered from prior chemotherapy (not including liver function)
  • More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
  • No concurrent chemotherapy
  • More than 2 weeks since prior radiotherapy
  • No prior radiotherapy to > 50% of the bone marrow
  • No concurrent radiotherapy
  • More than 3 weeks since prior surgery
  • No prior bortezomib
  • No concurrent antiretroviral therapy for HIV-positive patients
  • No other concurrent investigational agents
  • Concurrent cytochrome P450 interacting agents are allowed provided they are used with caution
  • Concurrent bisphosphonate therapy allowed (e.g., pamidronate or zoledronate), except during course 1 of bortezomib administration
  • ECOG 0-2
  • Fertile patients must use effective contraception during and for 30 days after study participation
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
80 participants (actual)

Study arms

  • Experimental
    Treatment

    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 · Other: pharmacological study

Interventions

  • Drugbortezomib

    Given IV

    Also known as: LDP 341, MLN341, VELCADE

  • Otherpharmacological study

    Correlative studies

    Also known as: pharmacological studies

06

What researchers measure

Primary outcomes

  1. DLT

    Time frame: 21 days

  2. MTD

    Time frame: 21 days

07

Study locations

3 sites
  • City of Hope Medical Center
    Duarte, California 91010, United States
  • Johns Hopkins University
    Baltimore, Maryland 21287-8936, United States
  • Wayne State University
    Detroit, Michigan 48202, United States
08

References and documents

Publications

  • LoRusso PM, Venkatakrishnan K, Ramanathan RK, Sarantopoulos J, Mulkerin D, Shibata SI, Hamilton A, Dowlati A, Mani S, Rudek MA, Takimoto CH, Neuwirth R, Esseltine DL, Ivy P. Pharmacokinetics and safety of bortezomib in patients with advanced malignancies and varying degrees of liver dysfunction: phase I NCI Organ Dysfunction Working Group Study NCI-6432. Clin Cancer Res. 2012 May 15;18(10):2954-63. doi: 10.1158/1078-0432.CCR-11-2873. Epub 2012 Mar 6. PubMed 22394984 ↗
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 16, 2013, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00091117
Lead sponsor
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Sep 8, 2004
Start date
Jul 2004
Primary completion
Mar 2013
Last update
Dec 16, 2013

Study contacts

Patricia LoRusso
principal investigator · Wayne State University
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Dec 2013. You cannot join it, but the record below documents what was studied.

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