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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

Tracking Information
First Submitted Date  ICMJE September 6, 2002
First Posted Date  ICMJE January 27, 2003
Last Update Posted Date October 16, 2009
Study Start Date  ICMJE March 2003
Actual Primary Completion Date July 2004   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 15, 2009)
  • Biologically effective dose of O(6)-benzylguanine administered continuously in pediatric patients with recurrent malignant glioma
  • Toxicities associated with the administration of O(6)-benzylguanine and carmustine implants.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 15, 2009)
Tumor response
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Carmustine Implants and O(6)-Benzylguanine in Treating Children With Recurrent Malignant Glioma
Official Title  ICMJE Phase I Trial of GLIADEL and O(6)-Benzylguanine in Pediatric Patients With Recurrent Malignant Gliomas
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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Primary Purpose: Treatment
Condition  ICMJE Brain and Central Nervous System Tumors
Intervention  ICMJE
  • Drug: O6-benzylguanine
  • Drug: polifeprosan 20 with carmustine implant
  • Procedure: adjuvant therapy
  • Procedure: conventional surgery
  • Procedure: neoadjuvant therapy
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: October 15, 2009)
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE July 2004
Actual Primary Completion Date July 2004   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE


  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 3 Years to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00045721
Other Study ID Numbers  ICMJE CDR0000257268
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party James M. Boyett/PBTC Operations and Biostatistics Center Executive Director, Pediatric Brain Tumor Consortium
Study Sponsor  ICMJE Pediatric Brain Tumor Consortium
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Ian F. Pollack, MD University of Pittsburgh
PRS Account Pediatric Brain Tumor Consortium
Verification Date October 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP