Glioblastoma Clinical Trial
Official title:
Bortezomib Sensitization of Recurrent Grade-4 Glioma With Unmethylated MGMT Promoter to Temozolomide Phase 1B/II Study
This phase IB/II 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.
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 tumour´s 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. ;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT05664243 -
A Phase 1b / 2 Drug Resistant Immunotherapy With Activated, Gene Modified Allogeneic or Autologous γδ T Cells (DeltEx) in Combination With Maintenance Temozolomide in Subjects With Recurrent or Newly Diagnosed Glioblastoma
|
Phase 1/Phase 2 | |
| Completed |
NCT02768389 -
Feasibility Trial of the Modified Atkins Diet and Bevacizumab for Recurrent Glioblastoma
|
Early Phase 1 | |
| Recruiting |
NCT05635734 -
Azeliragon and Chemoradiotherapy in Newly Diagnosed Glioblastoma
|
Phase 1/Phase 2 | |
| Completed |
NCT03679754 -
Evaluation of Ad-RTS-hIL-12 + Veledimex in Subjects With Recurrent or Progressive Glioblastoma, a Substudy to ATI001-102
|
Phase 1 | |
| Completed |
NCT01250470 -
Vaccine Therapy and Sargramostim in Treating Patients With Malignant Glioma
|
Phase 1 | |
| Terminated |
NCT03927222 -
Immunotherapy Targeted Against Cytomegalovirus in Patients With Newly-Diagnosed WHO Grade IV Unmethylated Glioma
|
Phase 2 | |
| Recruiting |
NCT03897491 -
PD L 506 for Stereotactic Interstitial Photodynamic Therapy of Newly Diagnosed Supratentorial IDH Wild-type Glioblastoma
|
Phase 2 | |
| Active, not recruiting |
NCT03587038 -
OKN-007 in Combination With Adjuvant Temozolomide Chemoradiotherapy for Newly Diagnosed Glioblastoma
|
Phase 1 | |
| Completed |
NCT01922076 -
Adavosertib and Local Radiation Therapy in Treating Children With Newly Diagnosed Diffuse Intrinsic Pontine Gliomas
|
Phase 1 | |
| Recruiting |
NCT04391062 -
Dose Finding for Intraoperative Photodynamic Therapy of Glioblastoma
|
Phase 2 | |
| Active, not recruiting |
NCT03661723 -
Pembrolizumab and Reirradiation in Bevacizumab Naïve and Bevacizumab Resistant Recurrent Glioblastoma
|
Phase 2 | |
| Active, not recruiting |
NCT02655601 -
Trial of Newly Diagnosed High Grade Glioma Treated With Concurrent Radiation Therapy, Temozolomide and BMX-001
|
Phase 2 | |
| Completed |
NCT02206230 -
Trial of Hypofractionated Radiation Therapy for Glioblastoma
|
Phase 2 | |
| Completed |
NCT03493932 -
Cytokine Microdialysis for Real-Time Immune Monitoring in Glioblastoma Patients Undergoing Checkpoint Blockade
|
Phase 1 | |
| Terminated |
NCT02709889 -
Rovalpituzumab Tesirine in Delta-Like Protein 3-Expressing Advanced Solid Tumors
|
Phase 1/Phase 2 | |
| Recruiting |
NCT06058988 -
Trastuzumab Deruxtecan (T-DXd) for People With Brain Cancer
|
Phase 2 | |
| Completed |
NCT03018288 -
Radiation Therapy Plus Temozolomide and Pembrolizumab With and Without HSPPC-96 in Newly Diagnosed Glioblastoma (GBM)
|
Phase 2 | |
| Not yet recruiting |
NCT04552977 -
A Trail of Fluzoparil in Combination With Temozolomide in Patients With Recurrent Glioblastoma
|
Phase 2 | |
| Withdrawn |
NCT03980249 -
Anti-Cancer Effects of Carvedilol With Standard Treatment in Glioblastoma and Response of Peripheral Glioma Circulating Tumor Cells
|
Early Phase 1 | |
| Withdrawn |
NCT02876003 -
Efficacy and Safety of G-202 in PSMA-Positive Glioblastoma
|
Phase 2 |