Ignite Creation Date:
2024-05-06 @ 11:55 AM
Last Modification Date:
2024-10-26 @ 12:51 PM
Study NCT ID:
NCT03631836
Status:
UNKNOWN
Last Update Posted:
2018-08-17
First Post:
2018-08-13
Brief Title:
Phase I Study of Monoclonal Antibondy GS 5745 an Matix Metalloproteinase 9 MMP9 Mab Inhibitor in Combination With Bevacizumab in Patients With Recurrent Glioblastoma
Sponsor:
Assistance Publique Hopitaux De Marseille
Organization:
Assistance Publique Hopitaux De Marseille
Study Overview
Official Title:
Phase I Study of Monoclonal Antibondy GS 5745 an Matix Metalloproteinase 9 MMP9 Mab Inhibitor in Combination With Bevacizumab in Patients With Recurrent Glioblastoma
Status:
UNKNOWN
Status Verified Date:
2018-08
Last Known Status:
NOT_YET_RECRUITING
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:
MARELLE01
Brief Summary:
Despite surgery and first-line standard of care which consist of radiotherapy with concomitant and adjuvant temozolomide all patients with glioblastoma GB will experience relapse At the time of recurrence therapeutic options include surgery or reirradiation in selected cases while in other cases bevacizumab approved by Food and Drug Administration FDA but not European Medicines Agency EMA is the preferred option worldwide Primary and acquired resistance to bevacizumab has been explored without definitive finding
Biomarkers able to predict response to antiangiogenic agents and particularly to bevacizumab are an unmet medical need We have showed that a low Matrix metallopeptidase 9 MMP9 or a high Matrix metallopeptidase 2 MMP2 baseline plasma levels were associated with a high response rate and a prolonged Progression-free survival PFS and overall survival OS in recurrent GB patients treated with bevacizumab but not with cytotoxic chemotherapy We also observed that MMP9 plasma level decreased during bevacizumab treatment and tend to increase at progression Finally in a retrospective analysis performed in the Avaglio trial a randomized phase III trial that tested bevacizumab versus placebo in addition to standard of care in patients with newly diagnosed glioblastoma a low plasma level of MMP9 at baseline predicted consistently PFS and OS gain associated to bevacizumab
These results are consistent with the role of MMP9 in vasculogenesis since MMP9 contribute to the recruitment of circulating endothelial and myeloid precursors an alternative vascularization process which is in part independent of the vascular endothelial growth factor VEGF pathway
Monoclonal Antibody GS 5745 is specifically directed against MMP9 First in human phase I study has been completed Development is ongoing
Our results strongly support a role for MMP9 in the primary or acquired resistance to bevacizumab Therefore we hypothesize that the Monoclonal Antibody GS5745 may overcome resistance to bevacizumab through a specific inhibition of MMP9 While a preclinical program is initiated in our lab the proposed phase I study is the first step to analyze the tolerance determine the recommended dose of the combination and explore the impact of GS5745 on MMP9 plasma levels and multimodal imaging in patients with recurrent glioblastoma
Objective
Determine the safety profile and tolerability of GS5745 given in combination with a fixed dose of bevacizumab in patients with recurrent GB in terms of Dose-Limiting Toxicities
Multicenter open label dose-finding study of GS5745 in combination with bevacizumab administered at a fixed dose both drugs will be administered once every two weeks for a total treatment duration of a maximum of 12 months
Before initiation of each new dose level a meeting between the sponsor the coordinator the investigators and an independent external expert will take place to decide jointly the next dose
Biomarkers able to predict response to antiangiogenic agents and particularly to bevacizumab are an unmet medical need We have showed that a low Matrix metallopeptidase 9 MMP9 or a high Matrix metallopeptidase 2 MMP2 baseline plasma levels were associated with a high response rate and a prolonged Progression-free survival PFS and overall survival OS in recurrent GB patients treated with bevacizumab but not with cytotoxic chemotherapy We also observed that MMP9 plasma level decreased during bevacizumab treatment and tend to increase at progression Finally in a retrospective analysis performed in the Avaglio trial a randomized phase III trial that tested bevacizumab versus placebo in addition to standard of care in patients with newly diagnosed glioblastoma a low plasma level of MMP9 at baseline predicted consistently PFS and OS gain associated to bevacizumab
These results are consistent with the role of MMP9 in vasculogenesis since MMP9 contribute to the recruitment of circulating endothelial and myeloid precursors an alternative vascularization process which is in part independent of the vascular endothelial growth factor VEGF pathway
Monoclonal Antibody GS 5745 is specifically directed against MMP9 First in human phase I study has been completed Development is ongoing
Our results strongly support a role for MMP9 in the primary or acquired resistance to bevacizumab Therefore we hypothesize that the Monoclonal Antibody GS5745 may overcome resistance to bevacizumab through a specific inhibition of MMP9 While a preclinical program is initiated in our lab the proposed phase I study is the first step to analyze the tolerance determine the recommended dose of the combination and explore the impact of GS5745 on MMP9 plasma levels and multimodal imaging in patients with recurrent glioblastoma
Objective
Determine the safety profile and tolerability of GS5745 given in combination with a fixed dose of bevacizumab in patients with recurrent GB in terms of Dose-Limiting Toxicities
Multicenter open label dose-finding study of GS5745 in combination with bevacizumab administered at a fixed dose both drugs will be administered once every two weeks for a total treatment duration of a maximum of 12 months
Before initiation of each new dose level a meeting between the sponsor the coordinator the investigators and an independent external expert will take place to decide jointly the next dose
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None