Bortezomib in Treating Patients With Recurrent Glioma

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. Identifier: NCT00006773
Recruitment Status : Terminated (Administratively complete.)
First Posted : January 27, 2003
Last Update Posted : January 24, 2013
Information provided by (Responsible Party):
National Cancer Institute (NCI)

December 6, 2000
January 27, 2003
January 24, 2013
May 2001
June 2007   (Final data collection date for primary outcome measure)
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 ]
Graded using the CTC version 2.0.
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Complete list of historical versions of study NCT00006773 on Archive Site
  • Biological effectiveness estimated using 20S proteosome activity [ Time Frame: Up to 6 years ]
    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 ]
    The proportion of patients with serious or life threatening toxicities will be estimated along with 95% confidence intervals.
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Bortezomib in Treating Patients With Recurrent Glioma
Phase I Evaluation of the Safety of PS 341 in the Treatment of Recurrent Gliomas
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


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.

Phase 1
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Adult Anaplastic Astrocytoma
  • Adult Anaplastic Oligodendroglioma
  • Adult Giant Cell Glioblastoma
  • Adult Glioblastoma
  • Adult Gliosarcoma
  • Recurrent Adult Brain Tumor
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
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.
Intervention: Drug: bortezomib
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
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June 2007   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
United States
U01CA062475 ( U.S. NIH Grant/Contract )
CDR0000068326 ( Registry Identifier: PDQ (Physician Data Query) )
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National Cancer Institute (NCI)
National Cancer Institute (NCI)
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Principal Investigator: Jeffrey Olson New Approaches to Brain Tumor Therapy Consortium
National Cancer Institute (NCI)
January 2013

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