Ignite Creation Date:
2024-05-05 @ 11:28 AM
Last Modification Date:
2024-10-26 @ 9:07 AM
Study NCT ID:
NCT00042991
Status:
COMPLETED
Last Update Posted:
2014-05-28
First Post:
2002-08-05
Brief Title:
Gefitinib and Radiation Therapy in Treating Children With Newly Diagnosed Gliomas
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
Phase III Trial of Gefitinib and Radiation in Pediatric Patients Newly Diagnosed With Brain Stem Tumors or Incompletely Resected Supratentorial Malignant Gliomas With Phase II Limited to Brain Stem Tumors
Status:
COMPLETED
Status Verified Date:
2012-12
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:
Biological therapies such as gefitinib may interfere with the growth of the tumor cells and may make the tumor cells more sensitive to radiation therapy This phase III trial is studying how well giving gefitinib together with radiation therapy works in treating children with newly diagnosed glioma
Detailed Description:
PRIMARY OBJECTIVES
I To define the safety of gefitinib administered in conjunction with irradiation in children with newly diagnosed non-disseminated diffuse intrinsic brainstem gliomas and newly diagnosed incompletely resected supratentorial malignant gliomas STMG not receiving enzyme inducing anticonvulsant drugs EIACDs
II To define the safety of gefitinib in children with newly diagnosed incompletely resected STMG receiving EIACDs
III To assess the safety and efficacy of gefitinib given with radiation therapy in children newly diagnosed with a brainstem glioma as measured by progression-free survival and to estimate the survival distribution
SECONDARY OBJECTIVES
I To compare hemodynamic magnetic resonance MR parameters to metabolic fludeoxyglucose F 18 FDG-positron emission tomography PET scanning and correlate both with clinical response or progression in this population
II To characterize the expression of ErbB1 receptors in tissue from STMG patients using immunohistochemistry and western blot assays
III To characterize the pharmacokinetics of gefitinib in the above patient groups and determine the effects of EIACD on the pharmacokinetics
IV To explore the pharmacogenetic polymorphisms for gefitinib eg CYP3A45 and BCRP and relate them to gefitinib pharmacokinetics and pharmacodynamics phenotype-genotype
OUTLINE This is a multicenter dose-escalation study of gefitinib Phase I closed to accrual effective 10272003 Patients are stratified according to the following
Stratum 1A Intrinsic brain stem glioma not receiving concurrent enzyme-inducing anticonvulsant drugs EIACDs Stratum 1B Incompletely resected supratentorial malignant gliomas STMG not receiving concurrent EIACDs Stratum 2 Incompletely resected STMG receiving concurrent EIACDs
Phase I portion patients in strata 1A 1B and 2 phase I closed to accrual effective 10272003 Patients receive oral gefitinib once daily Treatment repeats every 4 weeks for 13 courses 1 year Patients also receive standard brain irradiation once daily 5 days a week for 6 weeks beginning concurrently with initiation of the first course of gefitinib Treatment continues in the absence of disease progression or unacceptable toxicity
Cohorts of 3-6 patients receive escalating doses of gefitinib until the maximum tolerated dose MTD is determined The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity
Phase II portion patients in stratum 1A Once the MTD or the recommended Phase-II dose is determined additional patients who have newly diagnosed brain stem gliomas BSG are treated at the MTD or the recommended Phase-II dose
Patients are followed for three months after the last protocol treatment for those enrolled strictly on the phase I component Patients contributing to the phase II portion are followed until the earliest of date of death or three years after initiation of protocol therapy
PROJECTED ACCRUAL Considering the seven dose levels to be investigated in three strata where each dose level can accrue up to six patients a total of 126 patients 42 for each strata may be accrued for this study within 2 years Phase I closed to accrual effective 10272003 A total of 40 patients including the patients treated at the maximum tolerated dose or the recommended Phase-II dose during Phase I will be accrued for phase II of this study within 10 months
I To define the safety of gefitinib administered in conjunction with irradiation in children with newly diagnosed non-disseminated diffuse intrinsic brainstem gliomas and newly diagnosed incompletely resected supratentorial malignant gliomas STMG not receiving enzyme inducing anticonvulsant drugs EIACDs
II To define the safety of gefitinib in children with newly diagnosed incompletely resected STMG receiving EIACDs
III To assess the safety and efficacy of gefitinib given with radiation therapy in children newly diagnosed with a brainstem glioma as measured by progression-free survival and to estimate the survival distribution
SECONDARY OBJECTIVES
I To compare hemodynamic magnetic resonance MR parameters to metabolic fludeoxyglucose F 18 FDG-positron emission tomography PET scanning and correlate both with clinical response or progression in this population
II To characterize the expression of ErbB1 receptors in tissue from STMG patients using immunohistochemistry and western blot assays
III To characterize the pharmacokinetics of gefitinib in the above patient groups and determine the effects of EIACD on the pharmacokinetics
IV To explore the pharmacogenetic polymorphisms for gefitinib eg CYP3A45 and BCRP and relate them to gefitinib pharmacokinetics and pharmacodynamics phenotype-genotype
OUTLINE This is a multicenter dose-escalation study of gefitinib Phase I closed to accrual effective 10272003 Patients are stratified according to the following
Stratum 1A Intrinsic brain stem glioma not receiving concurrent enzyme-inducing anticonvulsant drugs EIACDs Stratum 1B Incompletely resected supratentorial malignant gliomas STMG not receiving concurrent EIACDs Stratum 2 Incompletely resected STMG receiving concurrent EIACDs
Phase I portion patients in strata 1A 1B and 2 phase I closed to accrual effective 10272003 Patients receive oral gefitinib once daily Treatment repeats every 4 weeks for 13 courses 1 year Patients also receive standard brain irradiation once daily 5 days a week for 6 weeks beginning concurrently with initiation of the first course of gefitinib Treatment continues in the absence of disease progression or unacceptable toxicity
Cohorts of 3-6 patients receive escalating doses of gefitinib until the maximum tolerated dose MTD is determined The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity
Phase II portion patients in stratum 1A Once the MTD or the recommended Phase-II dose is determined additional patients who have newly diagnosed brain stem gliomas BSG are treated at the MTD or the recommended Phase-II dose
Patients are followed for three months after the last protocol treatment for those enrolled strictly on the phase I component Patients contributing to the phase II portion are followed until the earliest of date of death or three years after initiation of protocol therapy
PROJECTED ACCRUAL Considering the seven dose levels to be investigated in three strata where each dose level can accrue up to six patients a total of 126 patients 42 for each strata may be accrued for this study within 2 years Phase I closed to accrual effective 10272003 A total of 40 patients including the patients treated at the maximum tolerated dose or the recommended Phase-II dose during Phase I will be accrued for phase II of this study within 10 months
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 |
|---|---|---|---|
| U01CA081457 | NIH | CTEP | httpsreporternihgovquickSearchU01CA081457 |
| NCI-2012-03022 | REGISTRY | None | None |
| PBTC-007 | OTHER | None | None |
| PBTC-007 | OTHER | None | None |