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

Study Overview
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Brief Summary
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This clinical trial is testing the safety and efficacy of NanO2TM administered via intravenous infusion in combination with standard radiation and chemotherapy. NanO2TM is being developed to increase the amount of oxygen delivered to tumors which is hoped to increase the effectiveness of radiation therapy.

Official Title
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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

Conditions
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Glioblastoma Multiforme

Intervention / Treatment
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* Drug: NanO2TM
* Drug: Placebo Saline Infusion


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NanO2TM<br>NanO2TM infusion in conjunction with Radiation Treatment and temozolomide | Drug: NanO2TM<br>* 0.1 mL/kg (2% w/vol emulsion)<br>* Other names: Dodecafluoropentane emulsion (DDFPe);|
| Placebo Comparator: Placebo<br>Placebo Saline infusion in conjunction with Radiation Treatment and temozolomide | Drug: Placebo Saline Infusion<br>* 0.1 mL/kg Saline Infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | To determine progression free survival (PFS) in newly-diagnosed glioblastoma patients after treatment with NVX-108 in combination with radiation and temozolomide (TMZ) | 22 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | To determine overall survival (OS) in newly-diagnosed glioblastoma patients after treatment with NanO2TM at the RD in combination with radiation and temozolomide.Neuro-oncology (RANO) criteria | 22 Months | 
| Response assessment by mRANO | To determine the objective response rate to study therapy using the modified Response Assessment in Neuro-oncology (mRANO) criteria | 22 Months | 
| Response assessment for pseudoprogression | To determine the effect of NanO2 on the timing of pseudoprogression occurrence | 22 Months | 
| To confirm that NanO2 re-oxygenation | Via TOLD MRI, we measure the oxygenation level in tumor tissue, to confirmd NanO2 treatment causes the re-oxygenation of hypoxic tissue | 22 Months | 
| To estimate the effect on the duration of functional independence | To estimate the effect on the duration of functional independence, as measured by the periodic measurement of Karnofsky Performance Scale | 22 Months | 
| Patient quality of life | To measure NanO2 treatment's impact on patient quality of life (score) by using FACT-Br | 22 Months | 
| Caregiver quality of life | To measure NanO2 treatment's impact on caregiver quality of life (score) by using questionnaires form CQOLC | 22 Months |