The Effects of NVX-108 as a Radiation Sensitizer in Glioblastoma

Inclusion criteria

• Histologically-confirmed newly-diagnosed glioblastoma multiforme.
• No prior treatment for glioblastoma apart from surgical resection.
• No prior treatment for glioblastoma apart from surgical resection.
• Planned for 60 Gray of focal radiation administered in 30 fractions, concurrently with temozolomide chemotherapy.
• Manageable risks associated with potential radiation necrosis in the radiation field, based on size of the field and proximity to eloquent brain regions (as assessed by the investigator).
• Aged 18-70 years.
• ECOG performance status 0-2.
• Life expectancy of at least 3 months.
• If receiving glucocorticoid therapy, the dose must be stable over at least 7 days prior to study enrollment.
• Archived tumor tissue available for central review.
• Able to undergo gadolinium-enhanced MRI (Gd-MRI) scans.
• Baseline MRI performed within 14 days before starting study treatment, while on a stable glucocorticoid dose for at least 5 days before and during the imaging study.
• Adequate hematologic, renal and hepatic function, as defined by:

Absolute neutrophil count (ANC) ≥ 1.5 109/L Platelet count ≥ 100 109/L Hemoglobin ≥ 90 g/L International normalized ratio (INR) and activated partial thromboplastin time (APTT) < 1.5 upper limit of normal (ULN) Plasma creatinine< 1.5 ULN Total bilirubin within normal limits (< 2.5 ULN if Gilbert's syndrome) AST and ALT < 2.5 ULN

• Patients who are women of childbearing potential or men (unless vasectomised) must agree to use a highly-effective method of birth control, such as hormonal contraceptive implants, combined oral contraceptives, an intrauterine device, a double-barrier method (eg. condom with a diaphragm) or abstinence, from study entry until 4 months after completing study therapy. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion criteria

• Presence of leptomeningeal disease or multifocal glioblastoma that cannot be encompassed within a feasible and safe radiation field.
• Intracranial bleeding, except for stable grade 1 hemorrhage.
• Has not recovered from the adverse effects of surgical resection or biopsy, except for neurological deficits.
• Patients who have received any other investigational agent within 4 weeks before enrollment.
• Stroke or transient ischemic attack within 6 months before enrollment.
• Myocardial infarction within 6 months before enrollment, unstable angina, New York Heart Association class II or greater congestive heart failure, or uncontrolled hypertension (systolic BP > 160 mmHg and/or diastolic BP > 100 mmHg).
• Congenital long QT syndrome.
• Clinically-significant chronic obstructive pulmonary disease or asthma.
• Active major infection requiring treatment.
• A history of other malignancies, except adequately treated non-melanoma skin cancer, curatively treated in-situ cancer or other solid tumors curatively treated with no evidence of disease for ≥ 2 years.
• Known infection with human immunodeficiency virus or hepatitis B or C virus.
• Current anticoagulant or antiplatelet therapy, except for prophylactic doses of low molecular weight heparins or low-dose aspirin.
• History of allergic reactions attributed to compounds of similar chemical composition to NVX-108.
• Women who are pregnant or breast feeding.
• Inability to comply with study procedures.
• History or evidence of any other clinically-significant condition that, in the opinion of the investigator, would pose a risk to subject safety or interfere with study procedures, evaluation or completion.