Adult Anaplastic Astrocytoma, Adult Anaplastic Oligodendroglioma, Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor
Conditions
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.
Interventions
DRUGbortezomib
Given IV
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Outcome results
None listed