Carmustine Implants and O(6)-Benzylguanine in Treating Children With Recurrent Malignant Glioma

This study has been terminated.
(Poor accrual)
Sponsor:
Collaborator:
Information provided by:
Pediatric Brain Tumor Consortium
ClinicalTrials.gov Identifier:
NCT00045721
First received: September 6, 2002
Last updated: October 15, 2009
Last verified: October 2009

September 6, 2002
October 15, 2009
March 2003
July 2004   (final data collection date for primary outcome measure)
  • Biologically effective dose of O(6)-benzylguanine administered continuously in pediatric patients with recurrent malignant glioma [ Designated as safety issue: Yes ]
  • Toxicities associated with the administration of O(6)-benzylguanine and carmustine implants. [ Designated as safety issue: Yes ]
Not Provided
Complete list of historical versions of study NCT00045721 on ClinicalTrials.gov Archive Site
Tumor response [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
Carmustine Implants and O(6)-Benzylguanine in Treating Children With Recurrent Malignant Glioma
Phase I Trial of GLIADEL and O(6)-Benzylguanine in Pediatric Patients With Recurrent Malignant Gliomas

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.

OBJECTIVES:

  • 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.

Interventional
Phase 1
Endpoint Classification: Safety Study
Primary Purpose: Treatment
Brain and Central Nervous System Tumors
  • Drug: O6-benzylguanine
  • Drug: polifeprosan 20 with carmustine implant
  • Procedure: adjuvant therapy
  • Procedure: conventional surgery
  • Procedure: neoadjuvant therapy
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
3
July 2004
July 2004   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

Age

  • 3 to 21

Performance status

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

Life expectancy

  • More than 8 weeks

Hematopoietic

  • 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

Hepatic

  • 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

Renal

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

Cardiovascular

  • No overt cardiac disease

Pulmonary

  • No overt pulmonary disease

Other

  • 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

PRIOR CONCURRENT THERAPY:

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)

Chemotherapy

  • 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

Radiotherapy

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

Surgery

  • See Disease Characteristics
  • Prior biopsy or cytoreductive surgery allowed

Other

  • Concurrent anticonvulsants allowed
  • No other concurrent anticancer or investigational drugs
Both
3 Years to 21 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00045721
CDR0000257268, PBTC-009
Yes
James M. Boyett/PBTC Operations and Biostatistics Center Executive Director, Pediatric Brain Tumor Consortium
Pediatric Brain Tumor Consortium
National Cancer Institute (NCI)
Study Chair: Ian F. Pollack, MD Children's Hospital of Pittsburgh
Pediatric Brain Tumor Consortium
October 2009

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