A Trial of 06-BG and BCNU in Children With CNS Tumors
O6-benzylguanine
+ carmustine
Brain Diseases+25
+ Brain Neoplasms
+ Central Nervous System Diseases
Treatment Study
Summary
Study start date: May 1, 1999
Actual date on which the first participant was enrolled.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.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.36 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Until 21 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
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
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.One single intervention group is designated in this study
This study does not include a placebo group
Treatment Groups
Group I
ExperimentalStudy Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 56 locations
University of Arkansas for Medical Sciences
Little Rock, United StatesOpen University of Arkansas for Medical Sciences in Google MapsUniversity of California San Diego Cancer Center
La Jolla, United StatesChildren's Hospital Los Angeles
Los Angeles, United StatesJonsson Comprehensive Cancer Center, UCLA
Los Angeles, United States