Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Bortezomib in Treating Patients With Recurrent Glioma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	18 and over	NCI	NABTT-9910 JHOC-NABTT-9910, NCT00006773

Objectives

1. 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.
2. Determine the biologic activity of this drug by measuring proteasome 20S activity in these patients .
3. Determine the effects of hepatic enzyme-inducing drugs, such as anticonvulsants, on biologic activity of this drug in these patients.

Entry Criteria

Disease Characteristics:

• 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

Prior/Concurrent Therapy:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered
• No more than 1 prior chemotherapy regimen

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 3 months since prior radiotherapy and recovered

Surgery:

• Not specified

Other:

• No other concurrent investigational agents

Patient Characteristics:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• Transaminases no greater than 4 times upper limit of normal

Renal:

• Creatinine no greater than 1.7 mg/dL

Other:

• 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

Expected Enrollment

A total of 42 patients will be accrued for this study within 14 months.

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.

Trial Contact Information

Trial Lead Organizations

New Approaches to Brain Tumor Therapy

Jeffrey Olson, MD, Protocol chair		Ph: 404-778-5770; 888-946-7447

Registry Information
Official Title		Phase I Evaluation of the Safety of PS 341 in the Treatment of Recurrent Gliomas
Trial Start Date		2001-01-02
Registered in ClinicalTrials.gov		NCT00006773
Date Submitted to PDQ		2000-12-05
Information Last Verified		2006-11-28
NCI Grant/Contract Number		CA006973, CA062475

Back to Top