|
||||||||||||||||||||||
|
|
Phase I Study of Temozolomide and O6-Benzylguanine in Pediatric Patients With Recurrent Brain Tumors
Alternate Title Temozolomide and O6-Benzylguanine in Treating Children With Recurrent Brain Tumors
Objectives
Entry Criteria Disease Characteristics:
Prior/Concurrent Therapy: Biologic therapy
Chemotherapy
Endocrine therapy
Radiotherapy
Surgery
Other
Patient Characteristics: Age
Performance status Life expectancy
Hematopoietic
[Note: *Transfusion independent] Hepatic
Renal
Cardiovascular
Pulmonary
Other
Expected Enrollment A total of 72 patients (18 per stratum) will be accrued for this study within 3 years. Outcomes Primary Outcome(s)Maximum tolerated dose (MTD) after first 4 weeks of treatment Best response rate from start of treatment until disease progression/recurrence or three months after completion of study treatment Outline This is a dose-escalation study of temozolomide with and without filgrastim (G-CSF). Patients are stratified according to prior radiotherapy (RT)/myeloablative therapy (no RT or focal RT vs craniospinal RT or myeloablative therapy). If neutropenia is the dose-limiting toxicity (DLT) for the first 2 strata, patients are further stratified according to concurrent G-CSF support (yes vs no). Patients receive O6-benzylguanine IV continuously on days 1 and 2 and oral temozolomide on day 1. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 2-6 patients in each stratum receive escalating doses of temozolomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 25% of patients experience DLT. Once the MTD is determined, 12 additional patients are treated at that dose. For courses 1-12, patients experiencing neutropenia may also receive G-CSF subcutaneously or IV daily beginning on day 3 and continuing until blood counts recover. Cohorts of 3-6 patients in each stratum receive escalating doses of temozolomide with G-CSF until the MTD is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience DLT. Once the MTD is determined, 6 additional patients are treated at that dose. Patients are followed every 3 months for 1 year and then every 6 months for 4 years. Published ResultsBroniscer A, Gururangan S, MacDonald TJ, et al.: Phase I trial of single-dose temozolomide and continuous administration of o6-benzylguanine in children with brain tumors: a pediatric brain tumor consortium report. Clin Cancer Res 13 (22 Pt 1): 6712-8, 2007.[PUBMED Abstract] Trial Lead Organizations Pediatric Brain Tumor Consortium
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. |
NCI Home |
Images Version |
Contact Us |
Policies |
Accessibility |
Viewing Files |
FOIA |
Site Help |
Site Map
|
A Service of the National Cancer Institute |