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Carmustine Implants and O(6)-Benzylguanine in Treating Children With Recurrent 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: NCT00045721
Recruitment Status : Terminated (Poor accrual)
First Posted : January 27, 2003
Last Update Posted : October 16, 2009
National Cancer Institute (NCI)
Information provided by:
Pediatric Brain Tumor Consortium

Brief Summary:

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Chemotherapy placed into the surrounding tissue after surgery to remove the tumor may kill any remaining tumor cells. O(6)-benzylguanine may increase the effectiveness of carmustine by making tumor cells more sensitive to the drug.

PURPOSE: Phase I trial to study the safety of combining O(6)-benzylguanine with carmustine implants in treating children who have recurrent malignant glioma.

Condition or disease Intervention/treatment Phase
Brain and Central Nervous System Tumors Drug: O6-benzylguanine Drug: polifeprosan 20 with carmustine implant Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy Phase 1

Detailed Description:


  • Determine the dose of O(6)-benzylguanine that reliably inhibits alkylguanine-DNA alkyltransferase activity in pediatric patients with recurrent malignant glioma.
  • Describe the toxic effects of O(6)-benzylguanine with carmustine implant (Gliadel) in these patients.
  • Investigate antitumor response in patients treated with this regimen.
  • Characterize the pharmacokinetics of O(6)-benzylguanine when administered continuously over a 9-day period.

OUTLINE: This is a multicenter, dose-escalation study of O(6)-benzylguanine.

Patients receive O(6)-benzylguanine (O6-BG) IV over 1 hour immediately followed by O6-BG IV continuously for 9 days. Two days after initiation of continuous infusion of O6-BG, patients undergo maximal tumor debulking. At the time of surgery, patients receive up to 8 polifeprosan 20 wafers with carmustine (Gliadel) implanted into the resection cavity.

Cohorts of up to 14 patients receive escalating doses of continuous infusion O6-BG until the optimally biologically effective dose (BED) is determined. The BED is defined as the dose at which at least 11 of 14 patients meet the target of complete suppression of alkylguanine-DNA alkyltransferase levels.

Patients are followed at day 11, at weeks 2, 4, 6, 8, and 12, at months 6, 9, and 12, every 6 months for 4 years, and then annually for 5 years.

PROJECTED ACCRUAL: Approximately 20 patients will be accrued for this study within 2 years.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Primary Purpose: Treatment
Official Title: Phase I Trial of GLIADEL and O(6)-Benzylguanine in Pediatric Patients With Recurrent Malignant Gliomas
Study Start Date : March 2003
Actual Primary Completion Date : July 2004
Actual Study Completion Date : July 2004

Primary Outcome Measures :
  1. Biologically effective dose of O(6)-benzylguanine administered continuously in pediatric patients with recurrent malignant glioma
  2. Toxicities associated with the administration of O(6)-benzylguanine and carmustine implants.

Secondary Outcome Measures :
  1. Tumor response

Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed progressive supratentorial anaplastic astrocytoma or glioblastoma multiforme
  • No multifocal disease or leptomeningeal dissemination of tumor
  • No evidence of tumor crossing midline
  • Limited intraventricular involvement
  • Measurable unilateral mass at least 10 mm by contrast-enhanced MRI
  • Received prior involved-field radiotherapy as a component of prior therapy
  • Amenable to and in need of significant debulking



  • 3 to 21

Performance status

  • Karnofsky 60-100% OR
  • Lansky 60-100%

Life expectancy

  • More than 8 weeks


  • Absolute neutrophil count greater than 1,000/mm3*
  • Platelet count greater than 100,000/mm3*
  • Hemoglobin greater than 8 g/dL (transfusions allowed) NOTE: * Transfusion independent


  • Bilirubin no greater than 1.5 times normal
  • AST and ALT less than 3 times normal
  • Albumin at least 2 g/dL
  • No overt hepatic disease


  • Creatinine clearance no greater than 1.5 times normal OR
  • Glomerular filtration rate greater than 70 mL/min
  • No overt renal disease


  • No overt cardiac disease


  • No overt pulmonary disease


  • Neurological deficits must be stable for at least the past week
  • No uncontrolled infection
  • No known hypersensitivity to nitrosoureas or polyethylene glycol
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception


Biologic therapy

  • At least 6 months since prior bone marrow transplantation
  • More than 2 weeks since prior colony-stimulating growth factors (e.g., filgrastim (G-CSF), sargramostim (GM-CSF), or epoetin alfa)


  • No more than 2 prior cytotoxic chemotherapy regimens
  • No more than 3 prior chemotherapy regimens total
  • More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered
  • Prior systemic carmustine (or other nitrosourea) allowed provided patient did not experience non-hematopoietic grade III/IV toxicity

Endocrine therapy

  • Concurrent dexamethasone allowed if on a stable dose for at least the past week


  • See Disease Characteristics
  • At least 3 months since prior radiotherapy
  • No prior craniospinal irradiation for metastatic disease


  • See Disease Characteristics
  • Prior biopsy or cytoreductive surgery allowed


  • Concurrent anticonvulsants allowed
  • No other concurrent anticancer or investigational drugs

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): NCT00045721

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United States, California
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94143-0372
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2970
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, 38105-2794
United States, Texas
Texas Children's Cancer Center
Houston, Texas, United States, 77030-2399
United States, Washington
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States, 98105
Sponsors and Collaborators
Pediatric Brain Tumor Consortium
National Cancer Institute (NCI)
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Study Chair: Ian F. Pollack, MD University of Pittsburgh
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Responsible Party: James M. Boyett/PBTC Operations and Biostatistics Center Executive Director, Pediatric Brain Tumor Consortium Identifier: NCT00045721    
Other Study ID Numbers: CDR0000257268
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: October 16, 2009
Last Verified: October 2009
Keywords provided by Pediatric Brain Tumor Consortium:
recurrent childhood cerebral astrocytoma
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, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors