Ignite Creation Date:
2024-05-05 @ 11:29 AM
Last Modification Date:
2024-10-26 @ 9:08 AM
Study NCT ID:
NCT00052780
Status:
COMPLETED
Last Update Posted:
2013-09-30
First Post:
2003-01-24
Brief Title:
Temozolomide and O6-Benzylguanine in Treating Children With Recurrent Brain Tumors
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
Phase I Trial of Temozolomide and O6-Benzylguanine in Pediatric Patients With Recurrent Brain Tumors
Status:
COMPLETED
Status Verified Date:
2013-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Phase I trial to study the safety of combining O6-benzylguanine with temozolomide in treating children who have recurrent or refractory brain tumors Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die O6-benzylguanine may increase the effectiveness of temozolomide by making tumor cells more sensitive to the drug
Detailed Description:
PRIMARY OBJECTIVES
I To determine the maximum tolerated dose of temozolomide Temodar when administered with O6-benzylguanine O6-BG with and without G-CSF support to pediatric patients with refractory brain tumors stratified by previous radiotherapy
SECONDARY OBJECTIVES
I To characterize the pharmacokinetics of temozolomide and O6-BG when used in combination
II To characterize toxicities associated with the combination of O6-BG and temozolomide with and without G-CSF support
III To document antitumor response in patients when treated with O6-BG and temozolomide
IV To determine the levels of MGMT enzyme and mismatch repair MMR proteins in tumor tissue investigating a possible correlation with patient outcome
OUTLINE This is a dose-escalation study of temozolomide with and without filgrastim G-CSF Patients are stratified according to prior radiotherapy RTmyeloablative therapy no RT or focal RT vs craniospinal RT or myeloablative therapy
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 additional patients are treated at that dose level for a total of 12 patients treated at the MTD
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
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 noCohorts 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 for resolution of all adverse events occurring while on treatment andor within 30 days of the last administration of study drug Patients will be followed for the shortest of 1 three months after the last protocol based treatment or 2 the date other therapy is initiated
I To determine the maximum tolerated dose of temozolomide Temodar when administered with O6-benzylguanine O6-BG with and without G-CSF support to pediatric patients with refractory brain tumors stratified by previous radiotherapy
SECONDARY OBJECTIVES
I To characterize the pharmacokinetics of temozolomide and O6-BG when used in combination
II To characterize toxicities associated with the combination of O6-BG and temozolomide with and without G-CSF support
III To document antitumor response in patients when treated with O6-BG and temozolomide
IV To determine the levels of MGMT enzyme and mismatch repair MMR proteins in tumor tissue investigating a possible correlation with patient outcome
OUTLINE This is a dose-escalation study of temozolomide with and without filgrastim G-CSF Patients are stratified according to prior radiotherapy RTmyeloablative therapy no RT or focal RT vs craniospinal RT or myeloablative therapy
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 additional patients are treated at that dose level for a total of 12 patients treated at the MTD
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
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 noCohorts 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 for resolution of all adverse events occurring while on treatment andor within 30 days of the last administration of study drug Patients will be followed for the shortest of 1 three months after the last protocol based treatment or 2 the date other therapy is initiated
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2012-03174 | REGISTRY | None | None |
| CDR653709 | None | None | None |
| PBTC-005 | OTHER | None | None |
| PBTC-005 | OTHER | None | None |
| U01CA081457 | NIH | CTEP | httpsreporternihgovquickSearchU01CA081457 |