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

Phase 1

Completed

• Conditions: Brain and Central Nervous System Tumors
• Interventions: Drug: O6-benzylguanine; Drug: carmustine

• 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.

Study Timeline

• Study Start: 1999-05
• Study First Submitted: 1999-11-01
• Study First Submitted QC: 2004-04-26
• Study First Posted: 2004-04-27
• Primary Completion: 2006-03
• Status Verified: 2007-10
• Last Update Submitted: 2013-02-04
• Last Update Posted: 2013-02-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

Not provided

Exclusion Criteria

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.

Trial Locations

Locations (56)

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, District of Columbia, United States

University of Florida Health Science Center; 🇺🇸 Gainesville, Florida, United States

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