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Phase I Evaluation of the Safety of PS 341 in the Treatment of Recurrent Gliomas

Phase 1
18 Years
Not Enrolling
Adult Anaplastic Astrocytoma, Adult Anaplastic Oligodendroglioma, Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor

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Trial Information

Phase I Evaluation of the Safety of PS 341 in the Treatment of Recurrent Gliomas


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

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.

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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose of bortezomib defined as the dose level below that at which > 1 of 3-6 patients experience DLT

Outcome Description:

Graded using the CTC version 2.0.

Outcome Time Frame:

3 weeks

Safety Issue:


Principal Investigator

Jeffrey Olson

Investigator Role:

Principal Investigator

Investigator Affiliation:

New Approaches to Brain Tumor Therapy Consortium


United States: Food and Drug Administration

Study ID:




Start Date:

May 2001

Completion Date:

Related Keywords:

  • Adult Anaplastic Astrocytoma
  • Adult Anaplastic Oligodendroglioma
  • Adult Giant Cell Glioblastoma
  • Adult Glioblastoma
  • Adult Gliosarcoma
  • Recurrent Adult Brain Tumor
  • Astrocytoma
  • Brain Neoplasms
  • Glioblastoma
  • Oligodendroglioma
  • Gliosarcoma



New Approaches to Brain Tumor Therapy Consortium Baltimore, Maryland  21231-1000