O6-Benzylguanine and Temozolomide in Treating Young Patients With Recurrent or Progressive Gliomas or Brain Stem Tumors

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: NCT00275002
Recruitment Status : Completed
First Posted : January 11, 2006
Results First Posted : August 9, 2011
Last Update Posted : July 31, 2014
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase II trial is studying how well giving O6-benzylguanine together with temozolomide works in treating young patients with recurrent or progressive gliomas or brain stem tumors. Drugs used in chemotherapy, such as O6-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. O6-benzylguanine may help temozolomide work better by making tumor cells more sensitive to the drug. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

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

Detailed Description:


I. Determine the sustained objective response rate to the combination of O6-benzylguanine and temozolomide in pediatric patients with recurrent or progressive high-grade gliomas and brain stem tumors.


I. Determine the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to tumor type (high-grade gliomas vs brain stem tumors).

Patients receive O6-benzylguanine IV over 1 hour followed by oral temozolomide on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed to the earliest of 30 days following discontinuation of therapy or the initiation of additional anti-cancer therapy or death.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 41 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of O6-Benzylguanine and Temozolomide in Pediatric Patients With Recurrent or Progressive High-Grade Gliomas and Recurrent or Progressive Brainstem Tumors
Study Start Date : February 2006
Actual Primary Completion Date : July 2010
Actual Study Completion Date : December 2010

Arm Intervention/treatment
Experimental: O6-BG and TMZ
O6-benzylguanine (O6-BG) and temozolomide (TMZ)
Drug: O6-benzylguanine
Dosing is based on the body surface area (BSA) calculated at the beginning of each course of therapy. O6-Benzylguanine, 120 mg/m^2, will be administered as a one-hour intravenous (IV) infusion, daily for 5 days. Four consecutive weeks will constitute one course. Courses will be repeated every 4 weeks for up to 12 courses of therapy.

Drug: temozolomide
Dosing is based on the body surface area (BSA) calculated at the beginning of each course of therapy. Temozolomide, 75 mg/m^2 (rounded to the nearest 5 mg, the size of the smallest capsule) will be given orally, 30 minutes following the completion of each infusion of O6-Benzylguanine. Four consecutive weeks will constitute one course. Courses will be repeated every 4 weeks for up to 12 courses.
Other Name: Temodar

Primary Outcome Measures :
  1. Percentage of Participants With an Objective Response (Complete Response or Partial Response) [ Time Frame: Week 8, 16, 24, 32, and 40 after starting therapy ]
    The primary endpoint is to assess the percentage of participants with a sustained objective response (complete response (CR) or partial response (PR)). Response is assessed by magnetic resonance imaging (MRI) per the following criteria: CR - disappearance of tumor and PR - ≥50% reduction in tumor based on the maximal cross-sectional measurements. The response must be sustained for at least 8 weeks, and the date of the confirmed sustained response is the date at which the response was first noted by MRI.

Secondary Outcome Measures :
  1. Number of Patients With Grade 3 or 4 Adverse Events at Least Possibly Related to the Combination of O6-benzylguanine and Temozolomide [ Time Frame: From day 1 of therapy up to 49 months ]
    Clinical and laboratory studies to assess adverse events are obtained at least every four weeks (prior to each course) with some laboratory studies obtained every 2 weeks. Adverse events are graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0). Attribution of each adverse event to the treatment regimen is determined by the participant's attending physician at the enrolling institution and verified by the study chair.

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Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Tumor: Participants must have a high-grade glioma (including e.g. histologically confirmed anaplastic astrocytoma, glioblastoma multiforme, anaplastic oligodendroglioma, anaplastic ganglioma, gliosarcoma) or a brainstem tumor (histologic confirmation waived) with documentation of disease recurrence or progression after treatment with standard therapy. Participants must have bi-dimensionally measurable disease, defined as at least 1 lesion that can be measured in ≥ 2 dimensions
  • Age: 21 years of age or less
  • Performance status: Karnofsky 60-100% (for patients > 16 years of age) or Lansky 60-100% (for patients ≤ 16 years of age)
  • Life expectancy: Not specified
  • Hematopoietic: Must have adequate bone marrow function defined as absolute neutrophil count > 1,500/mm^3, platelet count > 100,000/mm^3 (unsupported), hemoglobin > 8 g/dL (may be supported), and absolute lymphocyte count ≥ 500/mm^3
  • Hepatic: Must have SGOT and SGPT ≤ 2.5 times upper limit of normal (ULN), bilirubin ≤ 1.5 times ULN, and no overt hepatic disease
  • Renal: Participants must have creatinine clearance ≥ 60 mL/min or creatinine based on age as follows: no greater than 0.8 mg/dL (for patients ≤ 5 years of age), no greater than 1.0 mg/dL (for patients 6 to 10 years of age), no greater than 1.2 mg/dL (for patients 11 to 15 years of age), or no greater than 1.5 mg/dL (for patients > 15 years of age). There must be no overt renal disease
  • Cardiovascular: Must have no overt cardiac disease
  • Pulmonary: Must have no overt pulmonary disease
  • Other: Female participants of childbearing potential must have a negative pregnancy test prior to study registration, and must avoid breast-feeding. Female and male participants of childbearing or child-fathering potential must use effective contraception
  • Bone Marrow Transplant: Must be at least 6 months since prior allogeneic bone marrow transplantation and at least 3 months since prior autologous bone marrow or stem cell transplantation
  • Growth Factors: Must be at least 2 weeks since prior colony-stimulating factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], or erythropoietin)
  • Prior Chemotherapy: Must have received last dose of myelosuppressive anticancer chemotherapy ≥ 3 weeks prior to study registration and ≥ 6 weeks for nitrosoureas. Must have received last dose of nonmyelosuppressive investigational agents or anticancer drugs ≥ 7 days prior to study registration. Participants who have received prior temozolomide are eligible
  • Concurrent Endocrine Therapy: Concurrent corticosteroid therapy is allowed
  • Prior Radiotherapy: Must have received last fraction of craniospinal irradiation and local irradiation to the primary tumor ≥ 12 weeks prior to study registration
  • Prior Therapy-Other: Must have recovered from all prior therapy


  • Must not have history of severe toxicity (≥ grade 3) associated with temozolomide
  • Must not be receiving other concurrent anticancer or investigational therapy
  • Must not have history of hypersensitivity to dacarbazine, temozolomide, or polyethylene glycol (PEG)
  • Must not have uncontrolled significant systemic illness including infection, or overt renal, hepatic, cardiac, or pulmonary disease
  • Must not be HIV positive

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): NCT00275002

United States, California
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2970
United States, Illinois
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States, 60614
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104-4318
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
Houston, Texas, United States, 77030-2399
Dan L. Duncan Cancer Center at Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Washington
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States, 98105
Sponsors and Collaborators
National Cancer Institute (NCI)
Study Chair: Katherine Warren, MD National Cancer Institute (NCI)

Responsible Party: National Cancer Institute (NCI) Identifier: NCT00275002     History of Changes
Obsolete Identifiers: NCT00291291
Other Study ID Numbers: NCI-2012-03050
CDR0000455561 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: January 11, 2006    Key Record Dates
Results First Posted: August 9, 2011
Last Update Posted: July 31, 2014
Last Verified: February 2013

Keywords provided by National Cancer Institute (NCI):
recurrent childhood brain stem glioma
recurrent childhood brain tumor

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