Protocol Number: 07-C-0052

Title:

A Phase 2 Study of O6-Benzylguanine (O(6)-BG) and Temozolomide in Patients with Glioblastoma Progressing at Least 3 Months After Completion of Primary Treatment with Radiation Therapy and Temozolomide

Number:

07-C-0052

Summary:

Background:

High grade gliomas represent an important cause of cancer morbidity and mortality in this country. Despite progress in neurosurgical and radiotherapeutic techniques, there has been little improvement in the overall prognosis of patients with high grade gliomas in the last 20 years. Standard chemotherapy is of limited benefit in this disease and thus new targets and agents with novel mechanisms of action are needed.

Temozolomide has become a standard treatment for patients with gliomas including glioblastoma. It is approved for first line treatment of glioblastoma in combination with radiation therapy and as second line treatment for patients with anaplastic astrocytoma. A primary mechanism of resistance to temozolomide is the repair of DNA damaging lesions by the protein Methylguanine Methyl Transferase (MGMT). O6-Benzylguanine (O6-BG) provides a competitive substrate for MGMT. Once an MGMT molecule is bound to O6-BG it becomes permanently unable to repair lesions caused by temozolomide. Thus, O6-BG may be able to reverse MGMT-mediated temozolomide resistance.

Objectives:

This study is designed to evaluate the response rate to 5 days of temozolomide combined with O6-BG in patients with glioblastomas who have progressed at least 12 weeks after completion of radiotherapy with temozolomide and are currently receiving standard post-radiotherapy temozolomide. The primary endpoint will be to evaluate the combination in patients who have been demonstrated to have MGMT positive tumors by immunohistochemistry. As a secondary endpoint, the response rate will also be determined in those patients who have MGMT negative tumors by immunohistochemistry.

Eligibility:

Patients with glioblastoma whose disease has progressed while receiving adjuvant temozolomide and at least 3 months after completing radiation therapy will be entered into a phase 2 study of temozolomide and O6-BG.

Design:

O6-BG 120 mg/m(2) will be administered intravenously over 1 hour for five consecutive days. For the first two cycles of therapy, temozolomide at a dose of 50 mg/m(2) will be administered orally, in a fasting state (minimum of 2 hours from last meal) within 60 minutes of the end of each infusion of O6-BG. In the absence of grade 3 or 4 hematologic toxicities, the dose will be escalated to 75 mg/m(2) for subsequent cycles. Temozolomide and O6-BG will be administered on days 1 to 5 of the treatment cycle with treatment cycles repeated every 28 days.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: No longer recruiting/follow-up only

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria: This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Special Instructions:

Currently Not Provided

Keyword(s):

Brain

Tumor

Cytotoxic

Intravenous

Chemotherapy

Recruitment Keyword(s):

Brain Tumor

Glioblastoma

Condition(s):

Glioblastoma Multiforme

Large Cell Glioblastoma

Glosarcoma

Investigational Drug(s):

O(6) Benzylguanine (06BG)

Investigational Device(s):

None

Interventions:

Drug: O(6) Benzylguanine (06BG)

Supporting Site:

National Cancer Institute

Contact(s):

This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Citation(s):

Soffietti R, Nobile M, Ruda R, Borgognone M, Costanza A, Laguzzi E, Mutani R. Second-line treatment with carboplatin for recurrent or progressive oligodendroglial tumors after PCV (procarbazine, lomustine, and vincristine) chemotherapy: a phase II study. Cancer. 2004 Feb 15;100(4):807-13

Prados MD, Warnick RE, Mack EE, Chandler KL, Rabbitt J, Page M, Malec M. Intravenous carboplatin for recurrent gliomas. A dose-escalating phase II trial. Am J Clin Oncol. 1996 Dec;19(6):609-12

Hochberg FH, Pruitt A. Assumptions in the radiotherapy of glioblastoma. Neurology. 1980 Sep;30(9):907-11

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department Clinical Research Informatics, CC.

Search The Studies | Help | Questions |
Clinical Center Home | NIH Home

National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 01/30/2009