MBM-02 (Tempol) is an HIF-1 and HIF-2 inhibitor that is being tested as an addition to standard of care treatment that includes radiotherapy and TMZ. MBM-02's ability to increase progression free survival and decrease side effects of TMZ and radiotherapy treatment will be assessed.
MBM-02 is an HIF-1 and HIF-2 inhibitor that has shown in animal models to turn back on the apoptosis process (cell death) in cancer. Hypoxia is well documented in most solid tumors (Vaupel et al., 1991). Acute, intermittent, and cycling hypoxia are associated with inadequate blood flow, whereas chronic hypoxia is the consequence of increased oxygen diffusion distance resulting from tumor expansion (Dewhirst et al., 2008). A study by Chen and colleagues (2015) showed that cycling hypoxia and chronic hypoxia are important tumor microenvironment phenomena that limit tumor response to chemotherapy in GBM. In hypoxic conditions observed in solid state tumors, the hypoxia inducible factors, HIF-1α and HIF-2α, are upregulated and transcribe a panel of genes associated with cancer survival and progression, such as vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor (PDGF), and glucose transporter 1 (GLUT1). These factors are essential for tumor survival, thereby increasing tumor progression and decreasing apoptosis. Without the functions of the HIF family of genes, solid-state tumors could not progress and would not survive. In both Chen et al. (2015) and Sourbier et al. (2012), researchers established that the active compound in MBM-02 is an inhibitor of both HIF-1α and HIF-2α. This is an open label multisite trial that will assess MBM-02's ability to increase progress free survival in patients receiving standard of care for glioblastoma.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
55
Study drug will be administered orally using the capsule formulation (200 mg). The study drug will be administered 7 days a week for the entire treatment period.
Georgetown
Washington D.C., District of Columbia, United States
Progression Free Survival
Clinical efficacy as measured by progression-free survival rate at six months (PFS-6). Progression-free survival will be defined as the number of days from the date of first dose to the date of earliest disease progression based on RANO criteria.
Time frame: baseline to 6 months
Overall Survival
Clinical efficacy as measured by the Overall Survival (OS) rate at 12 months, 18 months, and 24 months.
Time frame: baseline to 24 months
Thrombocytopenia
Reduction in thrombocytopenia as measured by platelet count.
Time frame: baseline to 12 months
Neutropenia
Reduction in neutropenia as measured by absolute neutrophil count
Time frame: baseline to 12 months
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