NanO2 for Glioblastoma

(RESTORE Trial)

Not currently recruiting at 11 trial locations

Overseen By Rong Wang, MBA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NuvOx LLC

Must be taking: Temozolomide

Must not be taking: Anticoagulants, Antiplatelets

Disqualifiers: Recurrent glioblastoma, Stroke, MI, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

What You Need to Know Before You Apply

What is the purpose of this trial?

This clinical trial tests a new treatment called NanO2TM, designed to boost oxygen delivery to tumors and enhance the effectiveness of radiation therapy. The study targets individuals with newly diagnosed glioblastoma, an aggressive brain cancer. Participants will receive either NanO2TM or a placebo alongside standard chemotherapy and radiation. This trial may suit someone recently diagnosed with glioblastoma who is about to begin radiation and chemotherapy. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those on certain anticoagulant or antiplatelet therapies, except for specific medications like low-dose aspirin and some others. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that NanO2TM is likely to be safe for humans?

Research has shown that NanO2TM has been promising in earlier studies. Previous trials indicate that patients generally tolerate NanO2TM well, with most not experiencing serious side effects. Another study found that a similar treatment, DDFPe, was safely administered to patients and helped increase oxygen levels in tumors. This is important because more oxygen can enhance the effectiveness of radiation therapy. Overall, existing evidence suggests that NanO2TM is safe for humans, with few side effects reported. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for glioblastoma?

Unlike the standard treatments for glioblastoma, which typically involve surgery, radiation, and the chemotherapy drug temozolomide, NanO2TM introduces a novel approach by enhancing oxygen delivery to tumors. This infusion works by increasing the oxygen levels within the tumor environment, potentially making cancer cells more vulnerable to radiation therapy. Researchers are excited about NanO2TM because it offers a new way to weaken cancer cells, potentially improving the effectiveness of existing treatments and offering hope for better outcomes in a condition known for being tough to treat.

What evidence suggests that NanO2TM might be an effective treatment for glioblastoma?

Research has shown that NanO2TM is designed to increase the oxygen supply to tumors, potentially enhancing the effectiveness of radiation therapy. In this trial, some participants will receive NanO2TM alongside radiation treatment and temozolomide, while others will receive a placebo saline infusion with the same treatments. Earlier studies demonstrated that NanO2TM improved low oxygen levels in patients with glioblastoma, a type of brain cancer. These studies used imaging to confirm that tumors received more oxygen, which is crucial for effective radiation treatment. This suggests that NanO2TM could enhance the effectiveness of standard radiation and chemotherapy for treating glioblastoma. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

Adults with newly diagnosed glioblastoma who can have MRI scans, have a life expectancy of at least 3 months, and are in good enough health to undergo radiation and chemotherapy. They must not be pregnant or breastfeeding, agree to use effective birth control, and cannot have had any prior treatment for glioblastoma or other significant medical conditions that could interfere with the trial.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document.

I agree to use effective birth control during and for 4 months after the study.

I had an MRI within the last week without increasing my steroid dose.

Exclusion Criteria

I do not have any serious bleeding in my brain.

I know I do not have HIV or hepatitis B/C.

My cancer has spread to the lining of my brain and cannot be safely targeted with radiation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive radiation therapy 5 days a week for 6 weeks, with either NanO2 or placebo infusions administered prior to radiation

6 weeks

5 visits per week (in-person)

Recovery

Participants undergo a recovery period following radiation therapy

4 weeks

Maintenance Chemotherapy

Participants receive six cycles of maintenance Temozolomide therapy on days 1 to 5 of each 28-day cycle

6 cycles of 28 days each

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 3 months for 3 years, then every 6 months for 2 years

What Are the Treatments Tested in This Trial?

Interventions

• NanO2TM

Trial Overview The trial is testing NanO2TM combined with standard radiation therapy and temozolomide chemotherapy. NanO2TM is designed to increase oxygen delivery to tumors which may enhance the effectiveness of radiation therapy against brain cancer.

How Is the Trial Designed?

Group I: NanO2TM Experimental Treatment 1 Intervention

NanO2TM infusion in conjunction with Radiation Treatment and temozolomide

Group II: Placebo Placebo Group 1 Intervention

Placebo Saline infusion in conjunction with Radiation Treatment and temozolomide

NanO2TM is already approved in United States, Canada for the following indications:

Approved in United States as NanO2 for:

• None approved; Orphan Drug Designation for glioblastoma and sickle cell anemia

Approved in Canada as NanO2 for:

• None approved; allowance for Phase Ib/II study in COVID-19 patients with respiratory distress

Who Is Running the Clinical Trial?

NuvOx LLC

Lead Sponsor

Trials

7

Recruited

610+

Published Research Related to This Trial

Gadofluorine is an effective gadolinium-based contrast agent that can label malignant glioma cells in vitro without the need for additional agents, enhancing their visibility in MRI scans.

The use of Gadofluorine does not adversely affect glioma cell proliferation or migration, making it a safe option for cellular labeling in research and potentially in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro labeling of glioma cells with gadofluorine M enhances T1 visibility without affecting glioma cell growth or motility. Nolte, IS., Gungor, S., Erber, R., et al.[2021]

5-aminolevulinic acid (5-ALA) is used in glioblastoma surgery to make tumors fluorescent, enhancing their visibility during surgical procedures.

When 5-ALA is transformed into protoporphyrin IX (PPIX), it emits red light under blue light stimulation, allowing surgeons to more accurately identify and remove tumor tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Glioblastoma, innovations in surgery]. Picart, T., Guyotat, J.[2023]

Intratracheal (IT) administration of perfluorocarbon (PFC) nanoparticles resulted in significant accumulation within lung tumors, demonstrating a localized delivery method that maintains high concentrations of the treatment directly at the tumor site for over 72 hours.

The study found that IT delivery of PFC nanoparticles did not adversely affect rabbit behavior or respiratory function, indicating a safe profile for this method of drug delivery in lung cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local Intratracheal Delivery of Perfluorocarbon Nanoparticles to Lung Cancer Demonstrated with Magnetic Resonance Multimodal Imaging. Wu, L., Wen, X., Wang, X., et al.[2018]

The HMC-FMX nanoparticle platform enables effective visualization of glioblastoma multiforme (GBM) tumors during surgery by crossing the blood-brain barrier and selectively accumulating in the tumor, which is crucial for complete tumor resection.

This platform not only aids in tumor visualization but also facilitates the delivery of chemotherapeutic drugs like paclitaxel and cisplatin directly into GBM tumors, leading to reduced tumor size and improved survival rates in mouse models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Near Infrared Fluorescent Nanoplatform for Targeted Intraoperative Resection and Chemotherapeutic Treatment of Glioblastoma. Reichel, D., Sagong, B., Teh, J., et al.[2023]

PFCE nanodroplets loaded with a cisplatin prodrug (PFCE@cisPt(iv)-Lip) effectively enhance tumor oxygenation, which is crucial for improving the efficacy of concurrent chemo-radiotherapy in solid tumors.

In mouse models, this treatment not only significantly suppressed tumor growth and prolonged survival but also did so without causing major toxic side effects, indicating its potential for safe clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perfluorocarbon nanodroplets stabilized with cisplatin-prodrug-constructed lipids enable efficient tumor oxygenation and chemo-radiotherapy of cancer. [2021]

Perfluorocarbon (PFC)-based oxygen nanoemulsions have shown significant efficacy in various medical applications, including improving oxygen delivery after heart attacks and strokes, protecting organs during surgery, and enhancing cancer therapies.

Recent advancements in PFC nanoemulsions, such as size-adjustable formulations and phase-shift technologies, allow for controlled oxygen delivery and targeted therapies, potentially improving safety and efficacy in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic oxygen delivery by perfluorocarbon-based colloids. Krafft, MP., Riess, JG.[2021]

Human neural stem cells (NSCs) can be effectively labeled with (19)F for magnetic resonance imaging (MRI), allowing for precise tracking and quantification in both laboratory and in vivo settings, with minimal impact on cell viability and function.

The study demonstrated that (19)F MRI can successfully visualize and correlate the location and density of implanted NSCs in the brain, providing a promising method for monitoring stem cell therapies aimed at treating neurological disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo tracking of human neural stem cells with 19F magnetic resonance imaging. Boehm-Sturm, P., Mengler, L., Wecker, S., et al.[2021]

5-ALA, used in fluorescence-guided surgery for glioblastoma, labels both neoplastic and nonneoplastic cells, raising questions about its specificity for identifying cancerous cells during surgery.

While 5-ALA effectively highlights GBM tumor tissue compared to normal brain tissue, its labeling is not exclusive to cancer cells, suggesting the need for further research to evaluate its effectiveness against other potential alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-cell analysis of 5-aminolevulinic acid intraoperative labeling specificity for glioblastoma. Liu, Z., Mela, A., Argenziano, MG., et al.[2023]

Using fluorine-19 MRI, researchers tracked the accumulation of perfluorocarbon nanoemulsions (PFCNEs) in tumors, finding that a concentration of 2-3 mg/mL significantly improved the effectiveness of high intensity focused ultrasound (HIFU) treatments.

The study demonstrated that the amount of PFCNE delivered directly influences the extent of tumor ablation, with histological analysis revealing varying levels of tissue necrosis based on PFCNE concentration, highlighting the potential of 19F MRI for optimizing tumor treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tracking Perfluorocarbon Nanoemulsion Delivery by 19F MRI for Precise High Intensity Focused Ultrasound Tumor Ablation. Shin, SH., Park, EJ., Min, C., et al.[2018]

Implantation of chemotherapeutic wafers after the surgical removal of malignant gliomas can lead to a median survival increase of 2 months compared to standard treatment, based on two controlled randomized studies.

However, this treatment did not show any benefit for patients with recurrent tumors, indicating that its efficacy may be limited to first-time surgical interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chemotherapeutic wafers in treatment of malignant cerebral glioma. Assessment of a Cochrane review]. Kosteljanetz, M., Poulsen, HS.[2013]

The NaviFUS device, which combines focused ultrasound with microbubbles, is being tested for its safety and feasibility in opening the blood-brain barrier in patients with recurrent glioblastoma, with a total of 6 patients enrolled in this first-in-human trial.

The study aims to assess the minimal side effects of this method and its potential to enhance the delivery of chemotherapy, paving the way for a future phase 2 trial to improve tumor control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuronavigation-guided focused ultrasound (NaviFUS) for transcranial blood-brain barrier opening in recurrent glioblastoma patients: clinical trial protocol. Chen, KT., Lin, YJ., Chai, WY., et al.[2022]

Fluorescence-guided surgery using protoporphyrin IX (PpIX) has become a standard treatment for malignant gliomas, significantly increasing the rate of gross total resections compared to traditional methods.

While this technique offers high specificity in identifying tumor boundaries, its sensitivity is lower in areas of poor tumor infiltration, indicating a need for further improvement in detecting infiltrative tumor cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5-Aminolevulinic Acid-Protoporphyrin IX Fluorescence-Guided Surgery of High-Grade Gliomas: A Systematic Review. Guyotat, J., Pallud, J., Armoiry, X., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02189109?term=AREA%5BBasicSearch%5D(nuvox-)&rank=5

The Effects of NVX-108 as a Radiation Sensitizer in ... NVX-108 is being developed to increase the amount of oxygen delivered to tumors which is hoped to increase the effectiveness of radiation therapy. Official ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37609003/

Dodecafluoropentane Emulsion as a Radiosensitizer in ... This study shows that DDFPe can be safely administered to patients, and it is the first-in-human study to show reversal of hypoxia in GBM as measured by TOLD ...

3. clin.larvol.com clin.larvol.com/trial-detail/NCT02189109

The Effects of NVX-108 as a Radiation Sensitizer in ... In this study, NanO2 was administered prior to each fraction of chemoradiation, and imaging validated reversal of tumor hypoxia.

4. asco.org asco.org/abstracts-presentations/ABSTRACT146212

An oxygenation agent and radiation sensitizer ... Data will be presented summarizing current safety, PK and preliminary efficacy results, as well as our progress in qualifying TOLD MRI as a potential ...

5. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/433855

A Study of NanO2™ Combined With Radiation and ... NanO2TM is being developed to increase the amount of oxygen delivered to tumors which is hoped to increase the effectiveness of radiation therapy. Read more.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03862430

NCT03862430 | A Study of NanO2™ Combined With ... This clinical trial is testing the safety and efficacy of NanO2TM administered via intravenous infusion in combination with standard radiation and chemotherapy.

7. reporter.nih.gov reporter.nih.gov/search/M0tw3toZIEG-OdFls5d6hQ/project-details/10654516

Project Details - NIH RePORTER Expected outcome: Successful completion of the Aims proposed in this study should confirm that NVX-108 re-oxygenates GBM and show improved survival in ...

8. britishjournalofcancerresearch.com britishjournalofcancerresearch.com/a-phase-double-blind-randomized-prospective-placebo-controlled-study-of-tm-combined-with-radiation-and-temozolomide-in-patients-with-newly-diagnosed-glioblastoma-multiforme-restore

A phase 2 Double-Blind, RandomizEd, Prospective ... Current results from the Phase Ib study of NanO2 in GBM subjects indicate that there are minimal adverse events in subjects, and a trend of improvement in the ...