Bortezomib in Treating Patients With Recurrent Glioma

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

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

Study Overview

• Status: Terminated
• Conditions: Adult Anaplastic Astrocytoma; Adult Anaplastic Oligodendroglioma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Recurrent Adult Brain Tumor
• Intervention / Treatment: Drug: bortezomib

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.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231-1000
      • New Approaches to Brain Tumor Therapy Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: MLN341; LDP 341; VELCADE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Jeffrey Olson, New Approaches to Brain Tumor Therapy Consortium

Study record dates

Study Major Dates

• Study Start: May 1, 2001
• Primary Completion (Actual): June 1, 2007

Study Registration Dates

• First Submitted: December 6, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): January 24, 2013
• Last Update Submitted That Met QC Criteria: January 23, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease Attributes; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Recurrence; Astrocytoma; Gliosarcoma; Oligodendroglioma; Antineoplastic Agents; Bortezomib
• Other Study ID Numbers: NCI-2012-02367; U01CA062475 (U.S. NIH Grant/Contract); NABTT-9910; CDR0000068326 (Registry Identifier: PDQ (Physician Data Query))