NanO2 treatment combined with radiation and chemotherapy for glioblastoma

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 study is testing if adding a new oxygen treatment to standard radiation and chemotherapy can help people with newly diagnosed glioblastoma feel better and improve their outcomes.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 87 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: NuvOx LLC (Industry-sponsored)
• Drugs / interventions: chemotherapy, radiation
• Locations: 12 sites (Tucson, Arizona and 11 other locations)
• Trial ID: NCT03862430 on ClinicalTrials.gov

What this trial studies

This clinical trial is evaluating the safety and effectiveness of NanO2TM, an oxygen-enhancing treatment, when administered intravenously alongside standard radiation therapy and Temozolomide chemotherapy in patients with newly diagnosed glioblastoma multiforme. Participants will be randomly assigned to receive either NanO2 infusions or saline infusions before radiation therapy, which will occur five days a week for six weeks. Following radiation, patients will undergo a recovery period and then receive maintenance chemotherapy for six cycles. The study includes regular follow-ups for up to five years to monitor outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with newly diagnosed glioblastoma multiforme who meet specific health criteria.

Not a fit: Patients with contraindications to MRI or those with a life expectancy of less than three months may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve the effectiveness of radiation therapy for glioblastoma patients, potentially leading to better survival rates.

How similar studies have performed: While the use of oxygen-enhancing treatments in conjunction with radiation therapy is a novel approach, similar studies have shown promise in improving treatment outcomes for cancer patients.

Eligibility criteria

Inclusion Criteria:

1. Histologically confirmed, newly diagnosed primary or secondary glioblastoma multiforme.
2. Treatment plan includes 60 Gy of focal radiation administered in 30 fractions, concurrently with temozolomide chemotherapy.
3. 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).
4. Aged 18 years and older.
5. Karnofsky Performance Status ≥ 70
6. Life expectancy of at least 3 months.
7. Able to undergo gadolinium-enhanced MRI (Gd-MRI) scans.
8. 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.
9. Adequate hematologic, renal and hepatic function, as defined by:

   1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
   2. Platelet count ≥ 75 x 109/L
   3. Hemoglobin ≥ 10.0 g/dl
   4. Serum creatinine \< 1.5 x ULN
   5. Total bilirubin within normal limits (≤ 2.5 x ULN if Gilbert's syndrome)
   6. Aspartate transaminase (AST) and Alanine transaminase (ALT) \< 2.5 x ULN
10. 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.
11. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

1. Recurrent Glioblastoma
2. Prior treatment for glioblastoma apart from surgical resection.
3. 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.
4. Presence of leptomeningeal disease that cannot be encompassed within a feasible and safe radiation field.
5. Intracranial bleeding, except for stable grade 1 hemorrhage or a post-operative bleed that is clearing.
6. Has not recovered from the adverse effects of surgical resection or biopsy, except for neurological deficits.
7. Subjects who have received any other investigational agent within 4 weeks before enrollment
8. Stroke or transient ischemic attack requiring hospitalization within 6 months before enrollment.
9. 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).
10. Known History of Congenital long QT syndrome (12-lead EKG is not required).
11. Clinically significant chronic obstructive pulmonary disease or asthma.
12. Active major infection requiring treatment.
13. 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.
14. Known infection with human immunodeficiency virus or hepatitis B or C virus (testing is not required).
15. Current anticoagulant or antiplatelet therapy, except for prophylactic doses of low molecular weight heparins, low-dose aspirin, rivaroxaban (Xarelto®), apixaban (Eliquis®), or dabigatran (Pradaxa®).
16. History of allergic reactions attributed to compounds of similar chemical composition to NanO2.
17. Women who are pregnant or breast feeding.
18. Inability to comply with study procedures.
19. 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.
20. Known hypersensitivity to any temozolomide component or to dacarbazine (DTIC).

Where this trial is running

Tucson, Arizona and 11 other locations

• Center for Neurosciences — Tucson, Arizona, United States (Recruiting)
• University of Arizona — Tucson, Arizona, United States (Recruiting)
• UC Irvine Health- Chao Family Comprehensive Cancer Center — Orange, California, United States (Recruiting)
• Providence St. John's Cancer Institute — Santa Monica, California, United States (Recruiting)
• Yale Cancer Center — New Haven, Connecticut, United States (Recruiting)
• St. Francis Medical Center, OSF Healthcare — Peoria, Illinois, United States (Recruiting)
• Ochsner Clinic Foundation — New Orleans, Louisiana, United States (Recruiting)
• Saint Luke's Cancer Institute — Kansas City, Missouri, United States (Recruiting)
• Atlantic Health System — Summit, New Jersey, United States (Recruiting)
• Duke University Medical Center — Durham, North Carolina, United States (Recruiting)
• University Hospitals Seidman Cancer Center — Cleveland, Ohio, United States (Recruiting)
• Inova Schar Cancer Institute — Fairfax, Virginia, United States (Recruiting)

Study contacts

• Study coordinator: Evan Unger, MD

Conditions Glioblastoma Multiforme