Ignite Creation Date:
2024-05-06 @ 11:57 AM
Last Modification Date:
2024-10-26 @ 12:52 PM
Study NCT ID:
NCT03643549
Status:
RECRUITING
Last Update Posted:
2024-02-29
First Post:
2018-08-21
Brief Title:
Bortezomib and Temozolomide in Recurrent Grade-4 Glioma Unmethylated MGMT Promoter BORTEM-17
Sponsor:
Haukeland University Hospital
Organization:
Haukeland University Hospital
Study Overview
Official Title:
Bortezomib Sensitization of Recurrent Grade-4 Glioma With Unmethylated MGMT Promoter to Temozolomide Phase 1BII Study
Status:
RECRUITING
Status Verified Date:
2024-02
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:
BORTEM-17
Brief Summary:
This phase IBII trial is designed to investigate the safety and survival benefits for patients with recurrent grade-4 with unmethylated MGMT promoter treated with Bortezomib and Temozolomide in a specific schedule
Detailed Description:
Patients harbouring tumours with functional O6 methylguanine DNA methyltransferase MGMT DNA repair enzyme efficiently repair the DNA damage inflicted by Temozolomide and gain limited benefit from this chemotherapy Bortezomib depletes the MGMT enzyme restoring the tumours susceptibility to Temozolomide if the chemotherapy is administered in the precise schedule when the MGMT enzyme is depleted Additionally Bortezomib inhibits the growth of tumour cells by blocking autophagy flux Temozolomide causes genotoxic stress in cancer cells that in turn respond by inducing protective processes such as autophagy If both autophagy and MGMT DNA repair enzyme are blocked a priori the efficacy of Temozolomide will be enhanced Thus pre-treating the tumour with Bortezomib prior to administration of Temozolomide leads to DNA repair enzyme depletion and blockade of autophagy-induced survival signals The combined effect will sensitize the tumour to therapy improve chemotherapy efficacy and prolong patient survival outcomes
Hypothesis Pretreatment with Bortezomib administered prior to Temozolomide will sensitize recurrent GBM with unmethylated MGMT promoter to standard TMZ in palliative setting
Objective
Assessment of safety and tolerability of Bortezomib administered with Temozolomide
Determining the optimal dose of TMZ when administered as combination therapy
Estimate the progression free survival PFS and overall survival OS of patients with recurrent or progressed glioblastoma after pre-treatment with Bortezomib prior to combination with Temozolomide
Key secondary objectives
Tumour response to the therapy assessed by RANO and NANO criteria
Determine physiological molecular and biochemical changes in blood and tumour tissue that correlate with treatment responses
Hypothesis Pretreatment with Bortezomib administered prior to Temozolomide will sensitize recurrent GBM with unmethylated MGMT promoter to standard TMZ in palliative setting
Objective
Assessment of safety and tolerability of Bortezomib administered with Temozolomide
Determining the optimal dose of TMZ when administered as combination therapy
Estimate the progression free survival PFS and overall survival OS of patients with recurrent or progressed glioblastoma after pre-treatment with Bortezomib prior to combination with Temozolomide
Key secondary objectives
Tumour response to the therapy assessed by RANO and NANO criteria
Determine physiological molecular and biochemical changes in blood and tumour tissue that correlate with treatment responses
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?:
False
Is an FDA AA801 Violation?:
None