Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Bortezomib in Treating Patients With Advanced Cancer and Liver Dysfunction

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00091117
Recruitment Status : Completed
First Posted : September 8, 2004
Last Update Posted : December 16, 2013
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE September 7, 2004
First Posted Date  ICMJE September 8, 2004
Last Update Posted Date December 16, 2013
Study Start Date  ICMJE July 2004
Actual Primary Completion Date March 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 5, 2013)
  • DLT [ Time Frame: 21 days ]
  • MTD [ Time Frame: 21 days ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Bortezomib in Treating Patients With Advanced Cancer and Liver Dysfunction
Official Title  ICMJE A Phase I Pharmacokinetic Study of PS-341 in Patients With Advanced Malignancies and Varying Degrees of Liver Dysfunction for the CTEPSponsored Organ Dysfunction Working Group
Brief 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.
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.]

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hepatic Complications
  • Malignant Neoplasm
Intervention  ICMJE
  • Drug: bortezomib
    Given IV
    Other Names:
    • LDP 341
    • MLN341
    • VELCADE
  • Other: pharmacological study
    Correlative studies
    Other Name: pharmacological studies
Study Arms  ICMJE 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.
Interventions:
  • Drug: bortezomib
  • Other: pharmacological study
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 5, 2013)
80
Original Enrollment  ICMJE Not Provided
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date March 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries Australia
 
Administrative Information
NCT Number  ICMJE NCT00091117
Other Study ID Numbers  ICMJE NCI-2009-00059
NCI-2009-00059 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000383782
C-2802
C-2802 ( Other Identifier: Wayne State University )
6432 ( Other Identifier: CTEP )
U01CA062487 ( U.S. NIH Grant/Contract )
U01CA062505 ( U.S. NIH Grant/Contract )
U01CA069853 ( U.S. NIH Grant/Contract )
U01CA062491 ( U.S. NIH Grant/Contract )
U01CA070095 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Patricia LoRusso Wayne State University
PRS Account National Cancer Institute (NCI)
Verification Date December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP