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O(6)-Benzylguanine in Treating Patients With Malignant Glioma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00002971
Recruitment Status : Completed
First Posted : May 5, 2003
Last Update Posted : June 27, 2018
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary:

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of O(6)-benzylguanine given before surgery to patients who have malignant glioma.

Condition or disease Intervention/treatment Phase
Brain and Central Nervous System Tumors Drug: O6-benzylguanine Phase 1

Detailed Description:


  • Determine the dose of O6-benzylguanine (O6-BG) that produces total depletion of tumor O6-alkylguanine-DNA alkyltransferase (AGT) levels in more than 90% of patients with cerebral anaplastic astrocytoma or glioblastoma multiforme.
  • Determine the qualitative and quantitative toxicities of O6-BG in this patient population.

OUTLINE: This is a dose escalation study.

Part I: The first cohort of 10 patients receives O6-benzylguanine (O6-BG) IV over 1 hour at dose level 1 beginning 6 hours prior to surgery. If at least 3 of 10 patients in the first cohort have detectable levels of O6-alkylguanine-DNA alkyltransferase (AGT), then a second cohort of 10 patients receives O6-BG as above at dose level 2. Dose escalation continues until at least 8 of 10 patients have undetectable AGT activity. At this point, 4 additional patients are accrued. If at least 11 of 14 patients at this dose level have undetectable levels of AGT, then this dose level constitutes the biologic modulatory dose of O6-BG. If less than 11 of 14 patients have undetectable levels of AGT, then 10 additional patients are treated at a higher dose. If at any time 3 or more patients at a dose level have detectable AGT activity, accrual is stopped at that dose level and patients are treated at the next higher dose level. (Part I closed to accrual effective 7/10/2000)

Part II: An additional cohort of 14 patients receives O6-BG at dose level 5 beginning 18 hours prior to surgery.

PROJECTED ACCRUAL: Part I of this study closed to accrual effective 7/10/2000. A total of 14 patients will be accrued for part II of this study at a rate of 3 patients per month.

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Study Type : Interventional  (Clinical Trial)
Primary Purpose: Treatment
Official Title: A Phase I Trial of Pre-Surgical O6-Benzylguanine in the Treatment of Patients With Malignant Glioma
Actual Study Start Date : June 19, 1997
Actual Primary Completion Date : February 20, 2003
Actual Study Completion Date : January 1, 2009

Information from the National Library of Medicine

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


  • Must be undergoing a diagnostic/therapeutic craniotomy for biopsy/resection of recurrent or newly diagnosed (or presumed) cerebral anaplastic astrocytoma or glioblastoma multiforme

    • Patients undergoing stereotactic biopsy or partial resection are eligible



  • 18 and over

Performance status:

  • SWOG 0-2 OR
  • Karnofsky 60-100%


  • WBC at least 3,500/mm3
  • Absolute neutrophil count at least 1,800/mm3
  • Platelet count at least 125,000/mm3
  • Hemoglobin at least 9 g/dL


  • Bilirubin less than 1.5 mg/dL
  • SGOT less than 2 times upper limit of normal


  • Creatinine less than 1.5 mg/dL OR
  • Creatinine clearance greater than 70 mL/min


  • No cardiovascular illnesses that cannot be adequately controlled with
  • appropriate therapy or would increase risk, e.g.:
  • Severe cardiac disease such as uncontrolled arrhythmias or conduction
  • defects
  • Major problems with edema (e.g., residual leg swelling from deep venous
  • thrombosis)
  • Recent coronary artery disease
  • Poorly controlled hypertension (systolic pressure greater than 180 mm Hg,
  • diastolic pressure greater than 110 mm Hg)


  • No other medical illnesses that cannot be adequately controlled with
  • appropriate therapy or would increase risk, e.g.:
  • Major problems with edema (e.g., Cushing's syndrome)
  • Major psychiatric illness
  • No other malignancy requiring active therapy
  • Not pregnant or nursing
  • Fertile patients must us effective contraception


Biologic therapy:

  • Not specified


  • Must have failed or received no prior treatment with a nitrosourea,
  • procarbazine, or temozolomide
  • No prior O6-benzylguanine
  • At least 4 weeks since prior chemotherapy and recovered

Endocrine therapy:

  • Not specified


  • At least 6 weeks since prior radiotherapy
  • No prior radiotherapy to greater than 10-20% of bone marrow


  • No concurrent therapy for any other malignancy
  • At least 2 weeks since other prior investigational drug

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00002971

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United States, California
Jonsson Comprehensive Cancer Center, UCLA
Los Angeles, California, United States, 90095-1781
UCSF Cancer Center and Cancer Research Institute
San Francisco, California, United States, 94143-0128
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0752
United States, Pennsylvania
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15213-3489
United States, Texas
Simmons Cancer Center - Dallas
Dallas, Texas, United States, 75235-9154
University of Texas - MD Anderson Cancer Center
Houston, Texas, United States, 77030-4009
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78284-7811
United States, Wisconsin
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792-6164
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
National Cancer Institute (NCI)
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Study Chair: Michael Prados, MD UCSF Medical Center at Parnassus
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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Identifier: NCT00002971    
Other Study ID Numbers: NABTC-9702
CDR0000065479 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: May 5, 2003    Key Record Dates
Last Update Posted: June 27, 2018
Last Verified: June 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
recurrent adult brain tumor
adult glioblastoma
adult anaplastic astrocytoma
adult giant cell glioblastoma
adult gliosarcoma
Additional relevant MeSH terms:
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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
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action