A Phase II Double-blind, RandomizEd, Prospective, Placebo Controlled STudy of NanO2TM Combined With Radiation and Temozolomide in Patients With Newly-diagnosed Glioblastoma multiformE: (RESTORE)

This is an interventional treatment trial for Glioblastoma Multiforme Read More

Inclusion Criteria:

1. Histologically-confirmed newly-diagnosed primary and secondary glioblastoma multiforme.
2. No prior treatment for glioblastoma apart from surgical resection.
3. Planned for 60 Gy of focal radiation administered in 30 fractions, concurrently with temozolomide chemotherapy.
4. 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).
5. Aged 18 years and older.
6. ECOG Performance Status 0-2.
7. Life expectancy of at least 3 months.
8. If receiving glucocorticoid therapy, the dose must be stable or decreasing over at least 7 days prior to study enrolment.
9. Archived tumor tissue (10 slides per patient) available for central review.
10. Able to undergo gadolinium-enhanced MRI (Gd-MRI) scans.
11. Baseline MRI performed within 28 days before starting study treatment, while on a stable glucocorticoid dose for at least 7 days before and during the imaging study.

12. 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) < 3 x ULN
13. 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. Should a study participant or their partner become pregnant or suspect a pregnancy they should inform the treating physician immediately.
14. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. Recurrent Glioblastoma
2. Presence of multifocal glioblastoma
3. Presence of leptomeningeal disease that cannot be encompassed within a feasible and safe radiation field.
4. Intracranial bleeding, except for stable grade 1 hemorrhage or a post-operative bleed that is clearing.
5. Has not recovered from the adverse effects of surgical resection or biopsy, except for neurological deficits.
6. Subjects who have received any other investigational agent for the treatment of GBM within 4 weeks before enrollment (Phase 0 compounds - e.g. microdoses of dye or drug are eligible).
7. Stroke or transient ischemic attack requiring hospitalization within 6 months before enrollment.
8. 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).
9. Known History of Congenital long QT syndrome (12-lead EKG is not required).
10. Clinically-significant chronic obstructive pulmonary disease or asthma.
11. Active major infection requiring treatment.
12. 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.
13. Known infection with human immunodeficiency virus or hepatitis B or C virus (testing is not required).
14. Current anticoagulant or antiplatelet therapy, except for prophylactic doses of low molecular weight heparins, low-dose aspirin, rivaroxaban (Xarelto®), apixaban (Eliquis®), or dabigatran (PRADAXA®).
15. History of allergic reactions attributed to compounds of similar chemical composition to NVX-108.
16. Women who are pregnant or breast feeding.
17. Inability to comply with study procedures
18. 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.
19. Known hypersensitivity to any temozolomide component or to dacarbazine (DTIC).