A Trial of 06-BG and BCNU in Children With CNS Tumors
N/A
21 Years
Both
Brain and Central Nervous System Tumors
Trial Information
A Trial of 06-BG and BCNU in Children With CNS Tumors
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.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically or cytologically proven CNS tumor that is refractory to conventional
therapy or for which no effective therapy is known
- Histological requirement may be waived for brainstem and optic gliomas
- Stratum 2: No bone marrow involvement
PATIENT CHARACTERISTICS:
- Age: 21 and under
- Performance status: Karnofsky 50-100% OR Lansky 50-100%
- Life expectancy: At least 8 weeks
- Absolute neutrophil count at least 1500/mm3
- Platelet count at least 100,000/mm3 (stratum 2: at least 125,000/mm3)
- Hemoglobin at least 8 g/dL
- Bilirubin less than 1.5 mg/dL
- SGOT/SGPT no greater than 2.5 times normal
- Creatinine or GFR normal for age
- If required, DLCO must be 80% of normal and patient old enough to cooperate for DLCO
test
- Neurologic deficits must be stable for at least 2 weeks prior to study
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 6 months after study
PRIOR CONCURRENT THERAPY:
- At least 7 days since prior biologic therapy or immunotherapy and recovered
- At least 6 months since prior bone marrow transplant (stratum 1 only)
- At least 7 days since prior growth factors
- No concurrent filgrastim (G-CSF) prophylaxis
- Stratum 2: No prior bone marrow transplantation
- At least 2 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosourea)
and recovered
- Stratum 2: No greater than 2 prior chemotherapy regimens
- No prior nitrosourea therapy
- If receiving dexamethasone, must be on stable or decreasing dose for at least 2 weeks
prior to study
- At least 2 weeks since prior local palliative radiotherapy (small port)
- At least 6 months since prior substantial bone marrow radiation, total body
irradiation, hemipelvic radiotherapy, or total abdominal/pelvic/chest or mantle/Y
ports radiotherapy
- Recovered from prior radiotherapy
- Stratum 2: No prior central axis radiation
- No other concurrent anticancer or investigational agents
Type of Study:
Interventional
Study Design:
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
Denise Adams, MD
Investigator Role:
Study Chair
Investigator Affiliation:
University of Vermont
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2012-01842
NCT ID:
NCT00003765
Start Date:
May 1999
Completion Date:
Related Keywords:
- Brain and Central Nervous System Tumors
- childhood craniopharyngioma
- childhood central nervous system germ cell tumor
- childhood oligodendroglioma
- childhood choroid plexus tumor
- recurrent childhood brain stem glioma
- recurrent childhood supratentorial primitive neuroectodermal tumor
- recurrent childhood visual pathway glioma
- recurrent childhood cerebellar astrocytoma
- recurrent childhood cerebral astrocytoma
- recurrent childhood medulloblastoma
- recurrent childhood ependymoma
- Nervous System Neoplasms
- Central Nervous System Neoplasms
Name | Location |
|---|---|
| Roswell Park Cancer Institute | Buffalo, New York 14263 |
| Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
| University of Texas - MD Anderson Cancer Center | Houston, Texas 77030-4009 |
| University of Michigan Comprehensive Cancer Center | Ann Arbor, Michigan 48109-0752 |
| Children's Hospital of Philadelphia | Philadelphia, Pennsylvania 19104 |
| Mayo Clinic Cancer Center | Rochester, Minnesota 55905 |
| Jonsson Comprehensive Cancer Center, UCLA | Los Angeles, California 90095-1781 |
| Stanford University Medical Center | Stanford, California 94305-5408 |
| Emory University Hospital - Atlanta | Atlanta, Georgia 30322 |
| Indiana University Cancer Center | Indianapolis, Indiana 46202-5265 |
| Johns Hopkins Oncology Center | Baltimore, Maryland 21287 |
| University of Minnesota Cancer Center | Minneapolis, Minnesota 55455 |
| University of Mississippi Medical Center | Jackson, Mississippi 39216-4505 |
| Washington University School of Medicine | Saint Louis, Missouri 63110 |
| Duke Comprehensive Cancer Center | Durham, North Carolina 27710 |
| Medical University of South Carolina | Charleston, South Carolina 29425-0721 |
| Simmons Cancer Center - Dallas | Dallas, Texas 75235-9154 |
| Robert H. Lurie Comprehensive Cancer Center, Northwestern University | Chicago, Illinois 60611 |
| Children's Hospital of Michigan | Detroit, Michigan 48201 |
| University of Texas Health Science Center at San Antonio | San Antonio, Texas 78284-7811 |
| Midwest Children's Cancer Center | Milwaukee, Wisconsin 53226 |
| University of California San Diego Cancer Center | La Jolla, California 92093-0658 |
| UCSF Cancer Center and Cancer Research Institute | San Francisco, California 94115-0128 |
| State University of New York - Upstate Medical University | Syracuse, New York 13210 |
| Vanderbilt Cancer Center | Nashville, Tennessee 37232-6838 |
| NYU School of Medicine's Kaplan Comprehensive Cancer Center | New York, New York 10016 |
| Boston Floating Hospital Infants and Children | Boston, Massachusetts 02111 |
| University of Florida Health Science Center | Gainesville, Florida 32610-0296 |
| University of Wisconsin Comprehensive Cancer Center | Madison, Wisconsin 53792 |
| Dana-Farber Cancer Institute | Boston, Massachusetts 02115 |
| University of Arkansas for Medical Sciences | Little Rock, Arkansas 72205 |
| University of Kansas Medical Center | Kansas City, Kansas 66160-7353 |
| Cancer Institute of New Jersey | New Brunswick, New Jersey 08901 |
| Hackensack University Medical Center | Hackensack, New Jersey 07601 |
| Children's Hospital Los Angeles | Los Angeles, California 90027-0700 |
| Children's Hospital of Orange County | Orange, California 92668 |
| Children's National Medical Center | Washington, District of Columbia 20010-2970 |
| Children's Mercy Hospital | Kansas City, Missouri 64108 |
| Children's Hospital Medical Center - Cincinnati | Cincinnati, Ohio 45229-3039 |
| Children's Hospital of Columbus | Columbus, Ohio 43205-2696 |
| Children's Hospital of Pittsburgh | Pittsburgh, Pennsylvania 15213 |
| Children's Hospital and Regional Medical Center - Seattle | Seattle, Washington 98105 |
| Cardinal Glennon Children's Hospital | Saint Louis, Missouri 63104 |
| University of Oklahoma Health Sciences Center | Oklahoma City, Oklahoma 73104 |
| Cook Children's Medical Center - Fort Worth | Fort Worth, Texas 76104 |
| Texas Children's Cancer Center | Houston, Texas 77030-2399 |
| Columbia Presbyterian Hospital | New York, New York 10032 |
| Children's Memorial Hospital, Chicago | Chicago, Illinois 60614 |
| Primary Children's Medical Center | Salt Lake City, Utah 84113-1100 |
| City of Hope National Medical Center | Los Angeles, California 91010 |
| Graham Children's Health Center | Asheville, North Carolina 28801 |
