Ignite Creation Date:
2024-05-06 @ 12:02 AM
Last Modification Date:
2024-10-26 @ 10:43 AM
Study NCT ID:
NCT01472731
Status:
COMPLETED
Last Update Posted:
2024-05-06
First Post:
2011-07-18
Brief Title:
Safety and Imaging Study of GC1008 in Glioma
Sponsor:
University Medical Center Groningen
Organization:
University Medical Center Groningen
Study Overview
Official Title:
Guiding GC1008 Treatment of Primary Brain Tumors by 89Zr-GC1008 PET Imaging
Status:
COMPLETED
Status Verified Date:
2024-05
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:
Brain tumors account for only 2 of all cancers but result in a disproportionate share of cancer morbidity and mortality The five-year survival rates for the most common histologic subtypes anaplastic astrocytoma and glioblastoma glioblastoma multiforme GBM are 30 and 10 respectively
Drugs affecting transforming growth factor-β TGF-β might be of great interest for malignant glioma treatment TGF-β is an oncogenic factor in advanced tumors where it induces proliferation angiogenesis invasion and metastasis as well as suppresses the antitumoral immune response In addition TGF-β and its TGF-β receptors TβRI and TβRII are overexpressed in GBMs TGF-β signaling is involved in multiple steps of GBM development GC1008 is an antibody that is capable of neutralizing TGF-β and may therefore offer a new treatment option for patients with malignant glioma
For therapeutic success it may be essential for GC1008 to reach the target site in this case located in the brain We will be able to prove this with 89Zr-GC1008 PET imaging This imaging method also allows quantification of the amount of GC1008 reaching the tumor
This study consists of 2 parts In part 1 patients with a suspicion of a malignant glioma undergo an 89Zr-GC1008 PET scan before standard surgicaltreatment In part 2 patients with relapsed malignant glioma will undergo an 89Zr-GC1008 PET scan and will be treated with GC1008 in a phase II study as there is no standard treatment for these patients
We hypothesize that GC1008 uptake in brain tumors can be visualized and quantified using the 89Zr-GC1008 PET scan and GC1008 might offer a new treatment option for patients with relapsed malignant gliomas
Drugs affecting transforming growth factor-β TGF-β might be of great interest for malignant glioma treatment TGF-β is an oncogenic factor in advanced tumors where it induces proliferation angiogenesis invasion and metastasis as well as suppresses the antitumoral immune response In addition TGF-β and its TGF-β receptors TβRI and TβRII are overexpressed in GBMs TGF-β signaling is involved in multiple steps of GBM development GC1008 is an antibody that is capable of neutralizing TGF-β and may therefore offer a new treatment option for patients with malignant glioma
For therapeutic success it may be essential for GC1008 to reach the target site in this case located in the brain We will be able to prove this with 89Zr-GC1008 PET imaging This imaging method also allows quantification of the amount of GC1008 reaching the tumor
This study consists of 2 parts In part 1 patients with a suspicion of a malignant glioma undergo an 89Zr-GC1008 PET scan before standard surgicaltreatment In part 2 patients with relapsed malignant glioma will undergo an 89Zr-GC1008 PET scan and will be treated with GC1008 in a phase II study as there is no standard treatment for these patients
We hypothesize that GC1008 uptake in brain tumors can be visualized and quantified using the 89Zr-GC1008 PET scan and GC1008 might offer a new treatment option for patients with relapsed malignant gliomas
Detailed Description:
Brain tumors account for only 2 of all cancers but result in a disproportionate share of cancer morbidity and mortality The five-year survival rates for the most common histologic subtypes anaplastic astrocytoma and glioblastoma glioblastoma multiforme GBM are 30 and 10 respectively
After surgery the standard treatment of malignant glioma is focused on cell death induction by DNA damage neglecting the fact that invasion into surrounding brain tissue is a fundamental feature of and the major reason for treatment failure
Drugs affecting transforming growth factor-β TGF-β might be of great interest for malignant glioma treatment The reason for this is the fact that TGF-β acts as a tumor suppressor in normal epithelial cells and early-stage tumors but transforms in an oncogenic factor in advanced tumors where it induces proliferation angiogenesis invasion and metastasis as well as suppresses the antitumoral immune response In addition TGF-β expression and its TGF-β receptors TβRI and TβRII are overexpressed in GBMs TGF-β signaling is involved in multiple steps of GBM development Golestaneh Mishra 2005 and invasion Wesolowska et al 2008 Plasma TGF-β levels are elevated in GBM patients and decrease after surgical tumor resection Schneider et al 2006 Progression-free survival and overall survival are worse for malignant glioma patients with high TGF-β signaling compared with glioma patients with low TGF-β signaling activity Bruna et al 2007 All these features make TGF-β a promising target molecule for biological treatment approaches for GBM Wick et al 2006 Phase III-studies with the TGF-β2-specific antisense oligodeoxynucleotide AP12009 in malignant glioma showed promising results Hau et al 2007 Another approach to target TGF-β is with monoclonal antibodies such as GC1008 GC1008 is a fully human IgG4 kappa monoclonal antibody capable of neutralizing all mammalian isoforms of TGF-β ie 1 2 and 3 For therapeutic success it may be essential for GC1008 to reach the target site in this case located in the brain Our own data with 89Zr-bevacizumab which is also an IgG showed that the VEGF directed antibody bevacizumab penetrates the brain and is localized in brain metastases We therefore expect GC1008 to reach the malignant glioma as well In order to initiate clinical trials with TGF-β antibody in these patients it would clearly be of great help to prove that the drug arrives at the tumor site 89Zr-GC1008 PET imaging will allow us to prove this In addition PET imaging allows quantification of the amount of GC1008 reaching the malignant glioma A phase II study with GC1008 in patients with relapsed malignant gliomas will be initiated as currently there is no standard treatment available for these patients
Study objectives
Part 1 Feasibility of 89Zr-GC1008 PET imaging in patients with suspicion of a malignant glioma to assess if GC1008 penetrates into the brain tumor and to quantify its uptake
Part 2 89Zr-GC1008 PET imaging in patients with relapsed malignant glioma and phase II extension study with therapeutic GC1008 in these patients
For part 1 12 patients will be included For part 2 12-20 patients will be included
After surgery the standard treatment of malignant glioma is focused on cell death induction by DNA damage neglecting the fact that invasion into surrounding brain tissue is a fundamental feature of and the major reason for treatment failure
Drugs affecting transforming growth factor-β TGF-β might be of great interest for malignant glioma treatment The reason for this is the fact that TGF-β acts as a tumor suppressor in normal epithelial cells and early-stage tumors but transforms in an oncogenic factor in advanced tumors where it induces proliferation angiogenesis invasion and metastasis as well as suppresses the antitumoral immune response In addition TGF-β expression and its TGF-β receptors TβRI and TβRII are overexpressed in GBMs TGF-β signaling is involved in multiple steps of GBM development Golestaneh Mishra 2005 and invasion Wesolowska et al 2008 Plasma TGF-β levels are elevated in GBM patients and decrease after surgical tumor resection Schneider et al 2006 Progression-free survival and overall survival are worse for malignant glioma patients with high TGF-β signaling compared with glioma patients with low TGF-β signaling activity Bruna et al 2007 All these features make TGF-β a promising target molecule for biological treatment approaches for GBM Wick et al 2006 Phase III-studies with the TGF-β2-specific antisense oligodeoxynucleotide AP12009 in malignant glioma showed promising results Hau et al 2007 Another approach to target TGF-β is with monoclonal antibodies such as GC1008 GC1008 is a fully human IgG4 kappa monoclonal antibody capable of neutralizing all mammalian isoforms of TGF-β ie 1 2 and 3 For therapeutic success it may be essential for GC1008 to reach the target site in this case located in the brain Our own data with 89Zr-bevacizumab which is also an IgG showed that the VEGF directed antibody bevacizumab penetrates the brain and is localized in brain metastases We therefore expect GC1008 to reach the malignant glioma as well In order to initiate clinical trials with TGF-β antibody in these patients it would clearly be of great help to prove that the drug arrives at the tumor site 89Zr-GC1008 PET imaging will allow us to prove this In addition PET imaging allows quantification of the amount of GC1008 reaching the malignant glioma A phase II study with GC1008 in patients with relapsed malignant gliomas will be initiated as currently there is no standard treatment available for these patients
Study objectives
Part 1 Feasibility of 89Zr-GC1008 PET imaging in patients with suspicion of a malignant glioma to assess if GC1008 penetrates into the brain tumor and to quantify its uptake
Part 2 89Zr-GC1008 PET imaging in patients with relapsed malignant glioma and phase II extension study with therapeutic GC1008 in these patients
For part 1 12 patients will be included For part 2 12-20 patients will be included
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 |
|---|---|---|---|
| 2010-021639-15 | EUDRACT_NUMBER | None | None |