NanO2 for Glioblastoma

(RESTORE Trial)

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

87 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment NanO2 for glioblastoma?

Research on similar treatments, like perfluorocarbon nanoparticles, shows they can be effectively delivered to tumors and enhance imaging and drug delivery, as seen in lung cancer studies. Additionally, perfluorocarbon nanoemulsions have been shown to improve tumor ablation in other cancer treatments, suggesting potential benefits for glioblastoma. ^{1 2 3 4 5}

Is NanO2 safe for use in humans?

Research on perfluorocarbon nanoparticles, similar to NanO2, shows they have been used safely in various medical applications, including improving lung function in infants and enhancing cancer treatments, without causing significant side effects. Studies indicate that these nanoparticles do not impact behavior or cause harmful changes in blood tests when administered in animals. ^{1 2 6 7 8}

What makes the drug NanO2 unique for treating glioblastoma?

NanO2, also known as Dodecafluoropentane, is unique because it is a perfluorocarbon (a type of chemical compound) that can enhance oxygen delivery to tissues, potentially improving the effectiveness of treatments like radiation therapy for glioblastoma, a type of brain cancer. Unlike traditional treatments, it may offer a novel mechanism by increasing oxygen levels in tumor tissues, which can make cancer cells more susceptible to treatment. ^{1 9 10 11 12}

What is the purpose of this trial?

This trial is testing a new treatment that delivers more oxygen to tumors. It aims to help patients with a specific type of brain cancer by making radiation therapy more effective. By increasing oxygen levels in the tumor, the treatment helps radiation work better at killing cancer cells.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. Australia pubmed.ncbi.nlm.nih.gov

Local Intratracheal Delivery of Perfluorocarbon Nanoparticles to Lung Cancer Demonstrated with Magnetic Resonance Multimodal Imaging. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Near Infrared Fluorescent Nanoplatform for Targeted Intraoperative Resection and Chemotherapeutic Treatment of Glioblastoma. [2023]

3. Australia pubmed.ncbi.nlm.nih.gov

Tracking Perfluorocarbon Nanoemulsion Delivery by 19F MRI for Precise High Intensity Focused Ultrasound Tumor Ablation. [2018]

4. Denmark pubmed.ncbi.nlm.nih.gov

[Chemotherapeutic wafers in treatment of malignant cerebral glioma. Assessment of a Cochrane review]. [2013]

5. China pubmed.ncbi.nlm.nih.gov

Neuronavigation-guided focused ultrasound (NaviFUS) for transcranial blood-brain barrier opening in recurrent glioblastoma patients: clinical trial protocol. [2022]

6. England pubmed.ncbi.nlm.nih.gov

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

7. Netherlands pubmed.ncbi.nlm.nih.gov

Therapeutic oxygen delivery by perfluorocarbon-based colloids. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

In vivo tracking of human neural stem cells with 19F magnetic resonance imaging. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

5-Aminolevulinic Acid-Protoporphyrin IX Fluorescence-Guided Surgery of High-Grade Gliomas: A Systematic Review. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Single-cell analysis of 5-aminolevulinic acid intraoperative labeling specificity for glioblastoma. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

In vitro labeling of glioma cells with gadofluorine M enhances T1 visibility without affecting glioma cell growth or motility. [2021]

12. France pubmed.ncbi.nlm.nih.gov

[Glioblastoma, innovations in surgery]. [2023]