Ignite Creation Date:
2024-05-05 @ 6:35 PM
Last Modification Date:
2024-10-26 @ 9:35 AM
Study NCT ID:
NCT00509431
Status:
COMPLETED
Last Update Posted:
2020-07-31
First Post:
2007-07-30
Brief Title:
Erlotinib and Sirolimus in Treating Patients With Recurrent Malignant Glioma
Sponsor:
Jonsson Comprehensive Cancer Center
Organization:
Jonsson Comprehensive Cancer Center
Study Overview
Official Title:
A Phase III Dual-Center Open-Label Trial of the Safety and Efficacy of Tarceva Erlotinib Hydrochloride Plus Sirolimus in Patients With Recurrent Malignant Glioma Not on P450-Inducing Anti-Epileptics
Status:
COMPLETED
Status Verified Date:
2016-02
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:
RATIONALE Erlotinib and sirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth
PURPOSE This phase III trial is studying the side effects and best dose of erlotinib when given together with sirolimus and to see how well they work in treating patients with recurrent malignant glioma
PURPOSE This phase III trial is studying the side effects and best dose of erlotinib when given together with sirolimus and to see how well they work in treating patients with recurrent malignant glioma
Detailed Description:
OBJECTIVES
Primary
Determine the maximum tolerated dose MTD and dose-limiting toxicity DLT of escalating doses of erlotinib hydrochloride in combination with sirolimus in adult patients with malignant glioma who are not receiving enzyme-inducing anti-epileptic drugs EIAED Phase I
Evaluate preliminary efficacy response rate RR progression-free survival PFS and overall survival OS of erlotinib hydrochloride and sirolimus combination therapy in glioblastoma multiforme GMBgliosarcoma GS patients who are not undergoing surgery at the time of recurrence or relapse dose-expansion arm Phase II
Evaluate molecular determinants of response to the combination of erlotinib hydrochloride and sirolimus especially the roles of the mutation of EGFR eg vIII mutant other somatic mutations of vIII and mutationdeletion of PTEN
Secondary
To characterize the safety and tolerability of erlotinib hydrochloride and sirolimus combination therapy in these patient populations
To characterize the single-dose and repeated-dose pharmacokinetic PK profiles of erlotinib hydrochloride in serum and sirolimus in whole blood combination therapy in these patient populations
To characterize in pre- andor post-treatment tumor samples when available expression levels of total and activated phosphorylated proteins relevant to the EGFR VEGFR and PI3KmTOR signaling pathways relevant downstream signaling network components EGFR and VEGFR-related ligands apoptosis TUNEL cell cycle control and proliferation
To assess pre- andor post-treatment tumor samples when available for DNA-based changes eg EGFR DNA amplification EGFR and EGFRvIII mutations and mutationsdeletions in the PTEN gene relevant to the molecular biology in GBM
OUTLINE Patients receive oral erlotinib hydrochloride and sirolimus once daily on days 1-28 Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity
Patients undergo tumor tissue and blood sample collection periodically for pharmacological and biological studies Samples are analyzed for concentrations of erlotinib hydrochloride and trough serum levels of sirolimus via HPLC EGFR EGFRvIII PTEN and the phospho-specific antibodies associated with the MAPK and PI3K pathways via IHC and EGFRvIII and sequencing of EGFR PTEN and other critical genes via PCR gene expression and SNP analysis Germline DNA will also be used to distinguish polymorphisms from somatic mutations in gene sequenced
After completion of study treatment patients are followed periodically
Primary
Determine the maximum tolerated dose MTD and dose-limiting toxicity DLT of escalating doses of erlotinib hydrochloride in combination with sirolimus in adult patients with malignant glioma who are not receiving enzyme-inducing anti-epileptic drugs EIAED Phase I
Evaluate preliminary efficacy response rate RR progression-free survival PFS and overall survival OS of erlotinib hydrochloride and sirolimus combination therapy in glioblastoma multiforme GMBgliosarcoma GS patients who are not undergoing surgery at the time of recurrence or relapse dose-expansion arm Phase II
Evaluate molecular determinants of response to the combination of erlotinib hydrochloride and sirolimus especially the roles of the mutation of EGFR eg vIII mutant other somatic mutations of vIII and mutationdeletion of PTEN
Secondary
To characterize the safety and tolerability of erlotinib hydrochloride and sirolimus combination therapy in these patient populations
To characterize the single-dose and repeated-dose pharmacokinetic PK profiles of erlotinib hydrochloride in serum and sirolimus in whole blood combination therapy in these patient populations
To characterize in pre- andor post-treatment tumor samples when available expression levels of total and activated phosphorylated proteins relevant to the EGFR VEGFR and PI3KmTOR signaling pathways relevant downstream signaling network components EGFR and VEGFR-related ligands apoptosis TUNEL cell cycle control and proliferation
To assess pre- andor post-treatment tumor samples when available for DNA-based changes eg EGFR DNA amplification EGFR and EGFRvIII mutations and mutationsdeletions in the PTEN gene relevant to the molecular biology in GBM
OUTLINE Patients receive oral erlotinib hydrochloride and sirolimus once daily on days 1-28 Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity
Patients undergo tumor tissue and blood sample collection periodically for pharmacological and biological studies Samples are analyzed for concentrations of erlotinib hydrochloride and trough serum levels of sirolimus via HPLC EGFR EGFRvIII PTEN and the phospho-specific antibodies associated with the MAPK and PI3K pathways via IHC and EGFRvIII and sequencing of EGFR PTEN and other critical genes via PCR gene expression and SNP analysis Germline DNA will also be used to distinguish polymorphisms from somatic mutations in gene sequenced
After completion of study treatment patients are followed periodically
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 |
|---|---|---|---|
| UCLA-0604104 | None | None | None |