O6-benzylguanine and Carmustine in Treating Children With Refractory CNS Tumors
- Conditions
- Brain and Central Nervous System Tumors
- Interventions
- Registration Number
- NCT00003765
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
Phase I trial to study the effectiveness of O6-benzylguanine and carmustine in treating children who have refractory CNS tumors. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.
- Detailed Description
OBJECTIVES:
I. Determine the maximum tolerated dose and the dose limiting toxicity of carmustine administered after O6-benzylguanine in children with refractory primary CNS tumors.
II. Determine a safe and tolerable dose of carmustine administered after O6-benzylguanine to be used in phase II studies.
III. Determine the pharmacokinetics of O6-benzylguanine and its metabolite, O6-benzyl-8-oxoguanine, in these patients.
IV. Seek preliminary evidence of antitumor activity of this regimen in these patients.
V. Evaluate the acute and chronic toxicities, and describe cumulative toxicity, in patients treated with multiple courses of this regimen.
OUTLINE: This is a dose escalation study of carmustine.
Patients receive O6-benzylguanine IV over 1 hour, then, 1 hour later, carmustine IV is administered over 1 hour. Treatment is repeated every 6 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients each receive escalating doses of carmustine until the maximum tolerated dose (MTD) is reached. The MTD is defined as the dose level at which fewer than 2 of 6 patients experience dose limiting toxicity (DLT). If myelosuppression is the DLT, stratum 1 is closed and patients are accrued to stratum 2. If neutropenia is the DLT in stratum 2, patients receive filgrastim (G-CSF) subcutaneously beginning on day 2 and continuing until blood counts recover. Patients are followed every 6 months for 4 years, then annually thereafter.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 36
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Arm I carmustine Patients receive O6-benzylguanine IV over 1 hour, then, 1 hour later, carmustine IV is administered over 1 hour. Treatment is repeated every 6 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients each receive escalating doses of carmustine until the maximum tolerated dose (MTD) is reached. The MTD is defined as the dose level at which fewer than 2 of 6 patients experience dose limiting toxicity (DLT). If myelosuppression is the DLT, stratum 1 is closed and patients are accrued to stratum 2. If neutropenia is the DLT in stratum 2, patients receive filgrastim (G-CSF) subcutaneously beginning on day 2 and continuing until blood counts recover. Arm I O6-benzylguanine Patients receive O6-benzylguanine IV over 1 hour, then, 1 hour later, carmustine IV is administered over 1 hour. Treatment is repeated every 6 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients each receive escalating doses of carmustine until the maximum tolerated dose (MTD) is reached. The MTD is defined as the dose level at which fewer than 2 of 6 patients experience dose limiting toxicity (DLT). If myelosuppression is the DLT, stratum 1 is closed and patients are accrued to stratum 2. If neutropenia is the DLT in stratum 2, patients receive filgrastim (G-CSF) subcutaneously beginning on day 2 and continuing until blood counts recover.
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (56)
Emory University Hospital - Atlanta
🇺🇸Atlanta, Georgia, United States
Simmons Cancer Center - Dallas
🇺🇸Dallas, Texas, United States
Indiana University Cancer Center
🇺🇸Indianapolis, Indiana, United States
Boston Floating Hospital Infants and Children
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Children's Hospital Medical Center - Cincinnati
🇺🇸Cincinnati, Ohio, United States
Texas Children's Cancer Center
🇺🇸Houston, Texas, United States
University of Minnesota Cancer Center
🇺🇸Minneapolis, Minnesota, United States
Duke Comprehensive Cancer Center
🇺🇸Durham, North Carolina, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Children's Memorial Hospital, Chicago
🇺🇸Chicago, Illinois, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Children's Hospital of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Stanford University Medical Center
🇺🇸Stanford, California, United States
University of Florida Health Science Center
🇺🇸Gainesville, Florida, United States
Jonsson Comprehensive Cancer Center, UCLA
🇺🇸Los Angeles, California, United States
Johns Hopkins Oncology Center
🇺🇸Baltimore, Maryland, United States
University of California San Diego Cancer Center
🇺🇸La Jolla, California, United States
Cardinal Glennon Children's Hospital
🇺🇸Saint Louis, Missouri, United States
Columbia Presbyterian Hospital
🇺🇸New York, New York, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
City of Hope National Medical Center
🇺🇸Los Angeles, California, United States
NYU School of Medicine's Kaplan Comprehensive Cancer Center
🇺🇸New York, New York, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Princess Margaret Hospital for Children
🇦🇺Perth, Western Australia, Australia
Children's Hospital of Orange County
🇺🇸Orange, California, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
State University of New York - Upstate Medical University
🇺🇸Syracuse, New York, United States
Children's Hospital of Michigan
🇺🇸Detroit, Michigan, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States
Vanderbilt Cancer Center
🇺🇸Nashville, Tennessee, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Primary Children's Medical Center
🇺🇸Salt Lake City, Utah, United States
Midwest Children's Cancer Center
🇺🇸Milwaukee, Wisconsin, United States
Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
UCSF Cancer Center and Cancer Research Institute
🇺🇸San Francisco, California, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Children's Hospital of Columbus
🇺🇸Columbus, Ohio, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
University of Wisconsin Comprehensive Cancer Center
🇺🇸Madison, Wisconsin, United States
Royal Children's Hospital
🇦🇺Parkville, Victoria, Australia
Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
Montreal Children's Hospital
🇨🇦Montreal, Quebec, Canada
Hopital Sainte Justine
🇨🇦Montreal, Quebec, Canada
Robert H. Lurie Comprehensive Cancer Center, Northwestern University
🇺🇸Chicago, Illinois, United States
University of Texas - MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Graham Children's Health Center
🇺🇸Asheville, North Carolina, United States
Cook Children's Medical Center - Fort Worth
🇺🇸Fort Worth, Texas, United States
Children's Hospital and Regional Medical Center - Seattle
🇺🇸Seattle, Washington, United States
Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States