Bortezomib in Treating Patients With Recurrent Glioma - Full Text View

Sponsor:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00006773

Purpose

RATIONALE: Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth.

PURPOSE: Phase I trial to study the effectiveness of bortezomib in treating patients who have recurrent glioma.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors	Drug: bortezomib	Phase I

Study Type:	Interventional
Study Design:	Primary Purpose: Treatment
Official Title:	Phase I Evaluation of the Safety of PS 341 in the Treatment of Recurrent Gliomas

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Bortezomib

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment:	42
Study Start Date:	January 2001

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.

PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study within 14 months.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

Karnofsky 60-100%

Life expectancy:

Not specified

Hematopoietic:

Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3

Hepatic:

Bilirubin no greater than 1.5 mg/dL
Transaminases no greater than 4 times upper limit of normal

Renal:

Creatinine no greater than 1.7 mg/dL

Other:

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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered
No more than 1 prior chemotherapy regimen

Endocrine therapy:

Not specified

Radiotherapy:

At least 3 months since prior radiotherapy and recovered

Surgery:

Not specified

Other:

No other concurrent investigational agents

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00006773

Locations

United States, Alabama
Lurleen Wallace Comprehensive Cancer at University of Alabama-Birmingham
Birmingham, Alabama, United States, 35294
United States, Georgia
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States, 30322
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
United States, Michigan
Josephine Ford Cancer Center at Henry Ford Hospital
Detroit, Michigan, United States, 48202
United States, North Carolina
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States, 27157-1096
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104-4283

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Study Chair:

Jeffrey J. Olson, MD

Winship Cancer Institute of Emory University

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Phuphanich S, Supko JG, Carson KA, Grossman SA, Burt Nabors L, Mikkelsen T, Lesser G, Rosenfeld S, Desideri S, Olson JJ. Phase 1 clinical trial of bortezomib in adults with recurrent malignant glioma. J Neurooncol. 2010 Oct;100(1):95-103. Epub 2010 Mar 8.

ClinicalTrials.gov Identifier:	NCT00006773 History of Changes
Other Study ID Numbers:	CDR0000068326, NABTT-9910, JHOC-NABTT-9910
Study First Received:	December 6, 2000
Last Updated:	March 12, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

recurrent adult brain tumor
adult glioblastoma
adult anaplastic astrocytoma

adult anaplastic oligodendroglioma
adult giant cell glioblastoma
adult gliosarcoma

Additional relevant MeSH terms:

Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Nervous System Diseases
Bortezomib

Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 09, 2012