Stage 1: Marizomib + Bevacizumab in WHO Gr IV GBM; Stage 2: Marizomib Alone; Stage 3: Combination of Marizomib and Bevacizumab

Glioblastoma Clinical Trial

Official title:
Phase 1, Multicenter, Open-label, Dose-escalation, Combination Study of Marizomib and Bevacizumab in Bevacizumab-Naïve Subjects With WHO Grade IV Malignant Glioma Followed by Phase 2 Studies of Single Agent Marizomib and Combination Marizomib and Bevacizumab, and Phase 1 Dose-Escalation Study of Enterally-administered Marizomib With Bevacizumab

Status Completed

Clinical Trial Summary

This is a Phase 1/2 clinical trial to evaluate a new combination of drugs, marizomib (MRZ) and bevacizumab (BEV; Avastin®), for the treatment of WHO Grade IV malignant glioma. The study population includes subjects who are in first or second relapse and who have not previously received any bevacizumab or other anti-angiogenic agent or proteasome inhibitor for treatment of malignant glioma. Part 1 Phase 1 evaluates the combination of MRZ and BEV, while Part 2 Phase 2 evaluates single-agent MRZ. Part 3 (Phase 2) includes a combination MRZ using intra-patient dose escalation, and BEV at a fixed dose. Part 4 Phase 1 evaluates MRZ through enteral administration, and BEV at a fixed dose. Part 5 Phase 1 evaluates the repeat-dose pharmacokinetics of MRZ administered IV with ECG.

Clinical Trial Description

One of the few treatment options currently FDA approved for recurrent WHO Grade IV malignant glioma is BEV. Additional treatment options are needed for these subjects. Published literature indicates that targeting the proteasome in glioma cells has shown significant anti-tumor activity. MRZ is a novel, second generation proteasome inhibitor that prevents the breakdown of proteins involved in signal transduction which blocks growth and survival of cancer cells. In-vitro studies of multiple glioma cell lines were highly sensitive to MRZ. MRZ had relatively little effect on neural stem/progenitor cells suggesting minimal neurotoxicity while significantly affecting both malignant glioma stem cells and glioma cell lines. Parts 1 and 2 of this trial have been completed with the Recommended Part 3 (Phase 2) Dose established at 0.8 mg/m2. Part 3 of this trial is enrolling at the MRZ RP2D determined in Phase 1 to assess the combination of MRZ and BEV activity and safety. Parts 1, 2, 3 and 4 of this trial have been completed with the Recommended Dose established at 0.8 mg/m2. Part 5 of this trial is enrolling. ;

Study Design

Related Conditions & MeSH terms

Clinical Trial Details

NCT number	NCT02330562
Study type	Interventional
Source	Celgene
Contact
Status	Completed
Phase	Phase 1/Phase 2
Start date	April 15, 2015
Completion date	June 2, 2021

View Details

See also
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
Withdrawn	`NCT03980249` - Anti-Cancer Effects of Carvedilol With Standard Treatment in Glioblastoma and Response of Peripheral Glioma Circulating Tumor Cells	Early Phase 1
Not yet recruiting	`NCT04552977` - A Trail of Fluzoparil in Combination With Temozolomide in Patients With Recurrent Glioblastoma	Phase 2
Terminated	`NCT02905643` - Discerning Pseudoprogression vs True Tumor Growth in GBMs