A Phase 2 Study of NanO2(TM) Combined With Radiation and Temozolomide in Patients With Newly Diagnosed GBM

Glioblastoma Multiforme Clinical Trial

— RESTORE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03862430
• Other study ID #: RESTORE-P2
• Status: Recruiting
• Phase: Phase 2
• Start date: March 31, 2023
• Est. completion date: September 30, 2025

Study information

• Verified date: May 2024
• Source: NuvOx LLC
• Contact: Evan Unger, MD
• Phone: 520-624-6688
• Email: eunger[@]nuvoxpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 87
• Est. completion date: September 30, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme

Intervention

Drug:
• NanO2TM
0.1 mL/kg NanO2 infusion
• Placebo Saline Infusion
Saline Infusion

Locations

Country	Name	City	State
United States	University Hospitals Seidman Cancer Center	Cleveland	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	Inova Schar Cancer Institute	Fairfax	Virginia
United States	Saint Luke's Cancer Institute	Kansas City	Missouri
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	UC Irvine Health- Chao Family Comprehensive Cancer Center	Orange	California
United States	Atlantic Health System	Summit	New Jersey
United States	Center for Neurosciences	Tucson	Arizona
United States	University of Arizona	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
NuvOx LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Response assessment for pseudoprogression	To determine the effect of NanO2 on the timing of pseudoprogression occurrence	22 Months
Secondary	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
Secondary	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
Secondary	Patient quality of life	To measure NanO2 treatment's impact on patient quality of life (score) by using FACT-Br	22 Months
Secondary	Caregiver quality of life	To measure NanO2 treatment's impact on caregiver quality of life (score) by using questionnaires form CQOLC	22 Months