Bortezomib in Treating Patients With Recurrent Glioma

This study has been terminated.
(Administratively complete.)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00006773
First received: December 6, 2000
Last updated: January 23, 2013
Last verified: January 2013
  Purpose

Phase I trial to study the effectiveness of bortezomib in treating patients who have recurrent glioma. Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth


Condition Intervention Phase
Adult Anaplastic Astrocytoma
Adult Anaplastic Oligodendroglioma
Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Recurrent Adult Brain Tumor
Drug: bortezomib
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Evaluation of the Safety of PS 341 in the Treatment of Recurrent Gliomas

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum tolerated dose of bortezomib defined as the dose level below that at which > 1 of 3-6 patients experience DLT [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]
    Graded using the CTC version 2.0.


Secondary Outcome Measures:
  • Biological effectiveness estimated using 20S proteosome activity [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    Simple descriptive measures will be used to examine the association between biological effect and the probability of toxicity and response.

  • Frequency of toxicity, graded using the CTC version 2.0 [ Time Frame: Up to 6 years ] [ Designated as safety issue: Yes ]
    The proportion of patients with serious or life threatening toxicities will be estimated along with 95% confidence intervals.


Enrollment: 42
Study Start Date: May 2001
Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (bortezomib)
Patients receive bortezomib IV over 3-5 seconds twice weekly for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE

Detailed Description:

OBJECTIVES:

I. Determine the maximum tolerated dose of bortezomib with or without anticonvulsant drugs known to be metabolized by the P450 hepatic enzyme complex in patients with recurrent glioma.

II. Determine the biologic activity of this drug by measuring proteasome 20S activity in these patients.

III. Determine the effects of hepatic enzyme-inducing drugs, such as anticonvulsants, on biologic activity of this drug in these patients.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to concurrent anticonvulsant drug use (phenytoin, carbamazepine, phenobarbital, primidone, or felbamate vs gabapentin, lamotrigine, valproic acid, or no anticonvulsant drugs).

Patients receive bortezomib IV over 3-5 seconds twice weekly for 2 weeks. Courses repeat every 3 weeks 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 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 10 additional patients are treated with bortezomib at the MTD. Patients are followed every 2 months.

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed progressive or recurrent malignant glioma

    • Anaplastic astrocytoma
    • Anaplastic oligodendroglioma
    • Glioblastoma multiforme
  • Prior low-grade gliomas that have progressed to high-grade after therapy allowed
  • Measurable disease by MRI or CT scan
  • Performance status - Karnofsky 60-100%
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Bilirubin no greater than 1.5 mg/dL
  • Transaminases no greater than 4 times upper limit of normal
  • Creatinine no greater than 1.7 mg/dL
  • Mini mental score at least 15
  • No concurrent serious infection or other medical illness that would preclude study participation
  • No other malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after study participation
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered
  • No more than 1 prior chemotherapy regimen
  • At least 3 months since prior radiotherapy and recovered
  • No other concurrent investigational agents
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00006773

Locations
United States, Maryland
New Approaches to Brain Tumor Therapy Consortium
Baltimore, Maryland, United States, 21231-1000
Sponsors and Collaborators
Investigators
Principal Investigator: Jeffrey Olson New Approaches to Brain Tumor Therapy Consortium
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00006773     History of Changes
Other Study ID Numbers: NCI-2012-02367, NABTT-9910, U01CA062475, CDR0000068326
Study First Received: December 6, 2000
Last Updated: January 23, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Astrocytoma
Brain Neoplasms
Glioblastoma
Oligodendroglioma
Gliosarcoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Bortezomib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014