Bortezomib in Treating Patients With Recurrent Glioma

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Terminated

CT.gov ID

NCT00006773

Collaborator

(none)

Enrollment

Location

Arm

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Adult Anaplastic Astrocytoma Adult Anaplastic Oligodendroglioma Adult Giant Cell Glioblastoma Adult Glioblastoma Adult Gliosarcoma Recurrent Adult Brain Tumor	Drug: bortezomib	Phase 1

Detailed Description

OBJECTIVES:

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

Study Design

Study Type:

Interventional

Actual Enrollment :

42 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

May 1, 2001

Actual Primary Completion Date :

Jun 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose of bortezomib defined as the dose level below that at which > 1 of 3-6 patients experience DLT [3 weeks]
Graded using the CTC version 2.0.

Secondary Outcome Measures

Biological effectiveness estimated using 20S proteosome activity [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 [Up to 6 years]
The proportion of patients with serious or life threatening toxicities will be estimated along with 95% confidence intervals.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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