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O(6)-Benzylguanine and Temozolomide in Treating Patients With Glioblastoma Multiforme That Did Not Respond to Previous Temozolomide and Radiation Therapy

This study has been completed.
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ) Identifier:
First received: February 15, 2007
Last updated: September 22, 2016
Last verified: September 2016

RATIONALE: Drugs used in chemotherapy, such as O(6)-benzylguanine and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects and how well giving O(6)-benzylguanine together with temozolomide works in treating patients with glioblastoma multiforme that did not respond to previous temozolomide and radiation therapy.

Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: O6-benzylguanine
Drug: temozolomide
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of O-Benzylguanine (O-BG) and Temozolomide in Patients With Glioblastoma Progressing at Least 3 Months After Completion of Primary Treatment With Radiation Therapy and Temozolomide

Resource links provided by NLM:

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Confirmed best objective tumor response rate (complete or partial response) in patients with methylguanine methyltransferase (MGMT)-positive tumors as assessed by immunohistochemistry (IHC)

Secondary Outcome Measures:
  • Objective tumor response rate in patients with MGMT-negative tumors as assessed by IHC
  • Toxicity as assessed by CTCAE v 3
  • Best overall response
  • Progression-free survival
  • Overall survival

Estimated Enrollment: 100
Study Start Date: December 2006
Study Completion Date: May 2010
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Detailed Description:


  • Determine the antitumor activity of O6-benzylguanine and temozolomide in patients with temozolomide-resistant methylguanine methyltransferase-positive or -negative glioblastoma multiforme previously treated with radiotherapy.
  • Determine, preliminarily, the toxicity of this regimen in these patients.

OUTLINE: Patients receive O6-benzylguanine IV over 1 hour and oral temozolomide once daily on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for at least 6 months.

PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study.


Ages Eligible for Study:   18 Years to 120 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed glioblastoma multiforme (GBM), including the following:

    • Small or large cell GBM
    • Gliosarcoma
  • Temozolomide-resistant disease, as defined by the following:

    • Unequivocal evidence of tumor progression after receiving adjuvant temozolomide therapy for 5 consecutive days every 28 days for ≥ 2 courses
  • Must have failed prior radiotherapy

    • Progression must be documented by MRI (while on a stable steroid dose for ≥ 5 days) ≥ 12 weeks after completion of radiotherapy
  • Must have paraffin-embedded tissue blocks or ≥ 4 unstained paraffin-embedded microscope slides available from diagnosis


  • Karnofsky performance status 60-100%
  • Life expectancy > 8 weeks
  • WBC ≥ 3,000/mm³
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 10 g/dL (transfusion allowed)
  • AST < 2 times upper limit of normal (ULN)
  • Bilirubin < 2 times ULN
  • Creatinine < 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min
  • No significant medical illness that, in the opinion of the investigator, would preclude study compliance
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No significant active cardiac, hepatic, renal, or psychiatric disease
  • No other known active malignancy except for nonmelanoma skin cancer or carcinoma in situ of the cervix
  • No active infection requiring IV antibiotics
  • No disease that would obscure toxicity or alter drug metabolism


  • See Disease Characteristics
  • Recovered from prior temozolomide
  • Prior resection of recurrent or progressive tumor allowed if all the following criteria are met:

    • Recovered from prior surgery
    • Residual disease after resection of recurrent tumor by CT scan or MRI (while on a stable steroid dose for ≥ 5 days) ≤ 96 hours OR ≥ 4 weeks after surgery
  • At least 12 weeks since prior radiotherapy
  • No other prior therapy (i.e., polifeprosan 20 with carmustine implant [Gliadel wafers] or nitrosoureas)
  • No other concurrent chemotherapy, radiotherapy, immunotherapy, or investigational agents
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00436436

United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182
NCI - Neuro-Oncology Branch
Bethesda, Maryland, United States, 20892-8200
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Howard A. Fine, MD NCI - Neuro-Oncology Branch
  More Information

Responsible Party: National Cancer Institute (NCI) Identifier: NCT00436436     History of Changes
Other Study ID Numbers: CDR0000529875  NCI-07-C-0052  AOI-NCI-07-C-0052 
Study First Received: February 15, 2007
Last Updated: September 22, 2016

Keywords provided by National Institutes of Health Clinical Center (CC):
adult giant cell glioblastoma
adult gliosarcoma
recurrent adult brain tumor
adult glioblastoma

Additional relevant MeSH terms:
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors processed this record on February 23, 2017