O6-benzylguanine and Carmustine in Treating Children With Refractory CNS Tumors

National Cancer Institute (NCI)36 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Brain and Central Nervous System Tumors

Interventions

O6-benzylguanineDRUG

carmustineDRUG

Eligibility

Sex: ALLMax age: 21 Years

Medical Language ↔ Plain English

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

Locations (56)

Data from ClinicalTrials.gov

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University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

University of California San Diego Cancer Center

La Jolla, California, United States

Children's Hospital Los Angeles

Los Angeles, California, United States

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, United States

City of Hope National Medical Center

Los Angeles, California, United States

Children's Hospital of Orange County

Orange, California, United States

UCSF Cancer Center and Cancer Research Institute

San Francisco, California, United States

Stanford University Medical Center

Stanford, California, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

University of Florida Health Science Center

Gainesville, Florida, United States

...and 46 more locations