Ignite Creation Date:
2024-05-05 @ 11:38 AM
Last Modification Date:
2024-10-26 @ 9:11 AM
Study NCT ID:
NCT00095940
Status:
COMPLETED
Last Update Posted:
2014-05-23
First Post:
2004-11-09
Brief Title:
Lapatinib in Treating Young Patients With Recurrent or Refractory Central Nervous System Tumors
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
Molecular Biology and Phase II Study of Lapatinib GW572016 in Pediatric Patients With Recurrent or Refractory Medulloblastoma Malignant Glioma or Ependymoma
Status:
COMPLETED
Status Verified Date:
2013-01
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:
This phase III trial studies lapatinib to see how well it works in treating young patients with recurrent or refractory central nervous system CNS tumors Lapatinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth
Detailed Description:
PRIMARY OBJECTIVES
I To estimate the MTD and describe the DLT of oral lapatinib GW572016 administered twice daily for 28 days to children with recurrent or refractory malignant brain tumors who are not receiving steroids Stratum 1 and to describe toxicities in those who are receiving steroids Stratum 2
II To test the ability of lapatinib GW572016 to inhibit ERBB receptor signaling in recurrent or refractory medulloblastomaPNET high-grade glioma or ependymomas
III To estimate the sustained objective response rates CR plus PR sustained for 8 weeks to lapatinib GW572016 administered continuously at the MTD 900 mgm2dose bid to children with recurrent or refractory medulloblastomaPNET high-grade glioma or ependymoma
SECONDARY OBJECTIVES
I To characterize the plasma pharmacokinetics of lapatinib GW572016 and tumor tissue lapatinib GW572016 concentration in children
II To assess the effect of steroids on the pharmacokinetics of lapatinib GW572016
III To explore the pharmacogenetic polymorphisms in lapatinib GW572016 metabolizing enzymes and relate these polymorphisms to the drug pharmacokinetics
IV To estimate the incidence of ERBB1 ERBB2 ERBB3 and ERBB4 expression and pathway activation in recurrent or refractory CNS tumors of childhood including ependymoma medulloblastomaPNET and glioma
V To identify additional genes both within and outside the canonical ERBB pathway that might act as determinants of response to lapatinib GW572016
VI To explore changes in PET and correlative magnetic resonance imaging in children receiving lapatinib Imaging studies may be combined across similar PBTC protocols to increase the power for detecting correlations among scans and associations with outcome
OUTLINE This is an open-label multicenter study Patients are stratified according to histology medulloblastomaprimitive neuroectodermal tumor vs high-grade glioma vs ependymoma
Molecular Biology Phase Patients randomized to receive lapatinib prior to surgery receive oral lapatinib twice daily for 7-14 days Surgery is performed after 7-14 days of lapatinib treatment For patients randomized to not receive lapatinib surgery is performed within 3 weeks of registration After surgical resection all molecular biology participants start lapatinib treatment within 10 days post-surgery The first dose of lapatinib post-surgery initiates course 1 Patients receive oral lapatinib twice daily on days 1-28 Treatment repeats every 28 days for up to 26 courses 2 years in the absence of disease progression or unacceptable toxicity
Lapatinib ContinuationPhase II Patients receive oral lapatinib twice daily on days 1-28 Treatment repeats every 28 days for up to 26 courses 2 years in the absence of disease progression or unacceptable toxicity
After completion of study treatment patients are followed for at least 30 days
I To estimate the MTD and describe the DLT of oral lapatinib GW572016 administered twice daily for 28 days to children with recurrent or refractory malignant brain tumors who are not receiving steroids Stratum 1 and to describe toxicities in those who are receiving steroids Stratum 2
II To test the ability of lapatinib GW572016 to inhibit ERBB receptor signaling in recurrent or refractory medulloblastomaPNET high-grade glioma or ependymomas
III To estimate the sustained objective response rates CR plus PR sustained for 8 weeks to lapatinib GW572016 administered continuously at the MTD 900 mgm2dose bid to children with recurrent or refractory medulloblastomaPNET high-grade glioma or ependymoma
SECONDARY OBJECTIVES
I To characterize the plasma pharmacokinetics of lapatinib GW572016 and tumor tissue lapatinib GW572016 concentration in children
II To assess the effect of steroids on the pharmacokinetics of lapatinib GW572016
III To explore the pharmacogenetic polymorphisms in lapatinib GW572016 metabolizing enzymes and relate these polymorphisms to the drug pharmacokinetics
IV To estimate the incidence of ERBB1 ERBB2 ERBB3 and ERBB4 expression and pathway activation in recurrent or refractory CNS tumors of childhood including ependymoma medulloblastomaPNET and glioma
V To identify additional genes both within and outside the canonical ERBB pathway that might act as determinants of response to lapatinib GW572016
VI To explore changes in PET and correlative magnetic resonance imaging in children receiving lapatinib Imaging studies may be combined across similar PBTC protocols to increase the power for detecting correlations among scans and associations with outcome
OUTLINE This is an open-label multicenter study Patients are stratified according to histology medulloblastomaprimitive neuroectodermal tumor vs high-grade glioma vs ependymoma
Molecular Biology Phase Patients randomized to receive lapatinib prior to surgery receive oral lapatinib twice daily for 7-14 days Surgery is performed after 7-14 days of lapatinib treatment For patients randomized to not receive lapatinib surgery is performed within 3 weeks of registration After surgical resection all molecular biology participants start lapatinib treatment within 10 days post-surgery The first dose of lapatinib post-surgery initiates course 1 Patients receive oral lapatinib twice daily on days 1-28 Treatment repeats every 28 days for up to 26 courses 2 years in the absence of disease progression or unacceptable toxicity
Lapatinib ContinuationPhase II Patients receive oral lapatinib twice daily on days 1-28 Treatment repeats every 28 days for up to 26 courses 2 years in the absence of disease progression or unacceptable toxicity
After completion of study treatment patients are followed for at least 30 days
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-2012-03007 | REGISTRY | None | None |
| PBTC-016 | OTHER | None | None |
| PBTC-016 | OTHER | None | None |