Last updated on August 2018

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

Brief description of study

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.

Detailed Study 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, and 3 of this trial have been completed with the Recommended Dose established at 0.8 mg/m2. Part 4 of this trial is enrolling.

Clinical Study Identifier: NCT02330562

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Daniela Bota, MD, PhD

Comprehensive Brain Tumor Program at the University of California, Irvine Medical Center
Irvine, CA United States
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Santosh Kesari, MD, PhD

John Wayne Cancer Institute at the Providence Saint John's Health Center
Santa Monica, CA United States
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Howard A Fine, MD

Brain Tumor Center at NewYork Presbyterian Hospital/Weill Cornell Medical Center
New York, NY United States
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Annick Desjardins, MD

The Preston Robert Tisch Brain Tumor Center at the Duke University Medical Center
Durham, NC United States
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Warren Mason, MD

Gerry and Nancy Pencer Brain Tumour Centre at Princess Margaret Hospital
Toronto, ON Canada
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