Clinical trial NCT00006773: Bortezomib in Treating Patients With Recurrent Glioma
Official title: Phase I Evaluation of the Safety of PS 341 in the Treatment of Recurrent Gliomas
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Adult Anaplastic Astrocytoma
Adult Anaplastic Oligodendroglioma
Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Recurrent Adult Brain Tumor
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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 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

Primary outcomes:
measure: Maximum tolerated dose of bortezomib defined as the dose level below that at which > 1 of 3-6 patients experience DLT
timeFrame: 3 weeks
Secondary outcomes:
measure: Biological effectiveness estimated using 20S proteosome activity
timeFrame: Up to 6 years
measure: Frequency of toxicity, graded using the CTC version 2.0
timeFrame: Up to 6 years
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: New Approaches to Brain Tumor Therapy Consortium
state: Maryland
Study officials:
affiliation: New Approaches to Brain Tumor Therapy Consortium
name: Jeffrey Olson
role: PRINCIPAL_INVESTIGATOR
References: