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)

• ClinicalTrials.gov Identifier: NCT03862430
• Recruitment Status: Recruiting
• First Posted: March 5, 2019
• Last Update Posted: January 24, 2024
• Sponsor: NuvOx LLC
• Information provided by (Responsible Party): NuvOx LLC

Tracking Information

• First Submitted Date: March 1, 2019
• First Posted Date: March 5, 2019
• Last Update Posted Date: January 24, 2024
• Actual Study Start Date: March 31, 2023
• Estimated Primary Completion Date: June 30, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 13, 2023)

Progression-Free Survival (PFS) [ Time Frame: 22 months ]

To determine progression free survival (PFS) in newly-diagnosed glioblastoma patients after treatment with NVX-108 in combination with radiation and temozolomide (TMZ)

Original Primary Outcome Measures (submitted: March 1, 2019)

• Progression-Free Survival (PFS) [ Time Frame: 22 months ]
  To determine progression free survival (PFS) in newly-diagnosed glioblastoma patients after treatment with NVX-108 in combination with radiation and temozolomide (TMZ)
• Overall Survival [ Time Frame: 22 months ]
  To determine overall survival (OS) in newly-diagnosed glioblastoma patients after treatment with NVX-108 at the RD in combination with radiation and temozolomide.

Current Secondary Outcome Measures (submitted: March 8, 2023)

• Overall Survival [ Time Frame: 22 Months ]
  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
• Response assessment by mRANO [ Time Frame: 22 Months ]
  To determine the objective response rate to study therapy using the modified Response Assessment in Neuro-oncology (mRANO) criteria
• Response assessment for pseudoprogression [ Time Frame: 22 Months ]
  To determine the effect of NanO2 on the timing of pseudoprogression occurrence
• To confirm that NanO2 re-oxygenation [ Time Frame: 22 Months ]
  Via TOLD MRI, we measure the oxygenation level in tumor tissue, to confirmd NanO2 treatment causes the re-oxygenation of hypoxic tissue
• To estimate the effect on the duration of functional independence [ Time Frame: 22 Months ]
  To estimate the effect on the duration of functional independence, as measured by the periodic measurement of Karnofsky Performance Scale
• Patient quality of life [ Time Frame: 22 Months ]
  To measure NanO2 treatment's impact on patient quality of life (score) by using FACT-Br
• Caregiver quality of life [ Time Frame: 22 Months ]
  To measure NanO2 treatment's impact on caregiver quality of life (score) by using questionnaires form CQOLC

Original Secondary Outcome Measures (submitted: March 1, 2019)

Objective Response Rate to study therapy [ Time Frame: 22 Months ]

To determine the objective response rate to study therapy using Response Assessment in Neuro-oncology (RANO) criteria

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief 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:
• 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

Brief 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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Glioblastoma Multiforme

Intervention

• Drug: NanO2TM
  0.1 mL/kg NanO2 infusion
  Other Name: Dodecafluoropentane emulsion (DDFPe)
• Drug: Placebo Saline Infusion
  Saline Infusion
  Other Name: 0.9N NaCl

Study Arms

• Experimental: NanO2TM
  NanO2TM infusion in conjunction with Radiation Treatment and temozolomide
  Intervention: Drug: NanO2TM
• Placebo Comparator: Placebo
  Placebo Saline infusion in conjunction with Radiation Treatment and temozolomide
  Intervention: Drug: Placebo Saline Infusion

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 29, 2021): 87
• Original Estimated Enrollment (submitted: March 1, 2019): 84
• Estimated Study Completion Date: September 30, 2025
• Estimated Primary Completion Date: June 30, 2025 (Final data collection date for primary outcome measure)

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Evan Unger, MD; 520-624-6688; eunger@nuvoxpharma.com

Contact: Rong Wang, MBA; 520-624-6688; rwang@nuvoxpharma.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03862430
• Other Study ID Numbers: RESTORE-P2
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: NuvOx LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: NuvOx LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: NuvOx LLC
• Verification Date: January 2024