A Study of NanO2™ Combined With Radiation and Temozolomide in Patients With Newly Diagnosed GBM

All study participants will receive standard care for GBM including Temozolomide and radiation therapy. Subjects will be randomized on a 2 to 1 basis to receive either NanO2 infusions or saline infusions immediately prior to standard radiation therapy. Radiation therapy is performed 5 days a week for 6 weeks.

Radiation therapy is followed 28 days of recovery, and then six cycles of maintenance Temozolomide therapy on days 1 to 5 of six 28 day cycles.

Follow up will be every 3 months for 3 years, and then every 6 months for another 2 years.

Inclusion criteria

• Histologically confirmed, newly diagnosed primary or secondary glioblastoma multiforme.
• Treatment plan includes 60 Gy 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 years and older.
• Karnofsky Performance Status ≥ 70
• Life expectancy of at least 3 months.
• Able to undergo gadolinium-enhanced MRI (Gd-MRI) scans.
• Baseline MRI performed within 7 days before starting study treatment while on a stable or decreasing glucocorticoid dose for at least 7 days before and during the imaging study.
• Adequate hematologic, renal and hepatic function, as defined by:

• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelet count ≥ 75 x 109/L
• Hemoglobin ≥ 10.0 g/dl
• Serum creatinine < 1.5 x ULN
• Total bilirubin within normal limits (≤ 2.5 x ULN if Gilbert's syndrome)
• Aspartate transaminase (AST) and Alanine transaminase (ALT) < 2.5 x ULN
• Women of childbearing potential or men with child-bearing potential partners (unless vasectomized) must agree to use a highly-effective method of birth control from study entry until 4 months after completing study therapy.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion criteria

• Recurrent Glioblastoma
• Prior treatment for glioblastoma apart from surgical resection.
• Presence of multi-focal glioblastoma disease that cannot be encompassed into a radiation treatment field that would be safely treated to the prescribed radiation dose.
• Presence of leptomeningeal disease that cannot be encompassed within a feasible and safe radiation field.
• Intracranial bleeding, except for stable grade 1 hemorrhage or a post-operative bleed that is clearing.
• Has not recovered from the adverse effects of surgical resection or biopsy, except for neurological deficits.
• Subjects who have received any other investigational agent within 4 weeks before enrollment
• Stroke or transient ischemic attack requiring hospitalization within 6 months before enrollment.
• Myocardial infarction (MI) within 6 months before enrolment, unstable angina, New York Heart Association (NYHA) class II or greater congestive heart failure, or uncontrolled hypertension (systolic BP > 160 mmHg and/or diastolic BP > 100 mmHg).
• Known History of Congenital long QT syndrome (12-lead EKG is not required).
• 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 cancers 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 (testing is not required).
• Current anticoagulant or antiplatelet therapy, except for prophylactic doses of low molecular weight heparins, low-dose aspirin, rivaroxaban (Xarelto®), apixaban (Eliquis®), or dabigatran (Pradaxa®).
• History of allergic reactions attributed to compounds of similar chemical composition to NanO2.
• 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.
• Known hypersensitivity to any temozolomide component or to dacarbazine (DTIC).