Bortezomib in Treating Patients With Recurrent Glioma

Adult Glioblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00006773
• Other study ID #: NCI-2012-02367
• Secondary ID: NABTT-9910U01CA0
• Status: Terminated
• Phase: Phase 1
• First received: December 6, 2000
• Last updated: January 23, 2013
• Start date: May 2001

Study information

• Verified date: January 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 42
• Est. primary completion date: June 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• bortezomib
Given IV

Locations

Country	Name	City	State
United States	New Approaches to Brain Tumor Therapy Consortium	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose of bortezomib defined as the dose level below that at which > 1 of 3-6 patients experience DLT	Graded using the CTC version 2.0.	3 weeks	Yes
Secondary	Biological effectiveness estimated using 20S proteosome activity	Simple descriptive measures will be used to examine the association between biological effect and the probability of toxicity and response.	Up to 6 years	No
Secondary	Frequency of toxicity, graded using the CTC version 2.0	The proportion of patients with serious or life threatening toxicities will be estimated along with 95% confidence intervals.	Up to 6 years	Yes