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
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Primary Purpose: Treatment
Official Title: Phase I Trial of GLIADEL and O(6)-Benzylguanine in Pediatric Patients With Recurrent Malignant Gliomas

Resource links provided by NLM:


Further study details as provided by Pediatric Brain Tumor Consortium:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • Tumor response [ Designated as safety issue: No ]

Enrollment: 3
Study Start Date: March 2003
Study Completion Date: July 2004
Primary Completion Date: July 2004 (Final data collection date for primary outcome measure)
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   3 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00045721

Locations
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
Investigators
Study Chair: Ian F. Pollack, MD Children's Hospital of Pittsburgh
  More Information

No publications provided

Responsible Party: James M. Boyett/PBTC Operations and Biostatistics Center Executive Director, Pediatric Brain Tumor Consortium
ClinicalTrials.gov Identifier: NCT00045721     History of Changes
Other Study ID Numbers: CDR0000257268, PBTC-009
Study First Received: September 6, 2002
Last Updated: October 15, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by Pediatric Brain Tumor Consortium:
recurrent childhood cerebral astrocytoma

Additional relevant MeSH terms:
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Nervous System Diseases
Carmustine
O(6)-benzylguanine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 22, 2014