Bevacizumab + Focused Ultrasound for Brain Tumors

Overseen By Arthur Lung, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: NaviFUS Corporation

Must not be taking: Anticoagulants, Antiplatelets

Disqualifiers: Multifocal tumors, Cardiovascular disease, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: up to 34 weeks

10 Participants Needed

Trial Summary

What is the purpose of this trial?

This will be a prospective, open-label, single-arm pilot study to investigate the safety and efficacy of Bevacizumab (BEV) in combination with microbubble (MB)-mediated FUS in patients with recurrent GBM. BEV represents the physician's best choice for the standard of care (SoC) in rGBM after previous treatment with surgery (if appropriate), standard radiotherapy with temozolomide chemotherapy, and with adjuvant temozolomide.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on corticosteroids, you must be on a stable or decreasing dose for at least 1 week before starting the trial. Additionally, you cannot be on anticoagulant or antiplatelet therapy within 1 week prior to beginning treatment.

What data supports the effectiveness of the treatment Bevacizumab + Focused Ultrasound for brain tumors?

Research shows that focused ultrasound can significantly enhance the delivery of bevacizumab into the brain, improving its effectiveness in treating brain tumors like glioblastoma. Additionally, focused ultrasound has been shown to safely open the blood-brain barrier, allowing better drug delivery to the brain. ^{1 2 3 4 5}

Is the combination of Bevacizumab and Focused Ultrasound safe for treating brain tumors?

Bevacizumab can cause serious side effects like bleeding in the brain and blood clots, especially in brain tumor patients. Focused ultrasound has been shown to be safe in animal studies, allowing drugs to reach the brain without harming normal functions. However, the safety of combining these treatments in humans needs more research. ^{5 6 7 8 9}

How is the treatment Bevacizumab + Focused Ultrasound for brain tumors different from other treatments?

This treatment is unique because it uses focused ultrasound to temporarily open the blood-brain barrier (a protective layer around the brain) to allow better delivery of Bevacizumab, a drug that targets blood vessel growth in tumors, directly into the brain, potentially enhancing its effectiveness against brain tumors. ^{1 2 3 5 10}

Eligibility Criteria

This trial is for patients with recurrent Glioblastoma Multiforme (rGBM) who have already undergone treatments like surgery, radiotherapy, and chemotherapy with temozolomide. It's not specified here, but typically participants should be in stable health otherwise.

Inclusion Criteria

Body mass index (BMI) ≥ 17 kg/m2

Patients should have a life expectancy ≥ 12 weeks

The central of FUS exposure region is located close to the cortex, with a minimum distance of at least 30 mm beneath the skull bone

Exclusion Criteria

Patients who have radiographic evidence of multifocal enhancing tumors

Patients with implanted electronic device in the brain

Patients who have psychiatric illness/social situations that would limit compliance with study requirements

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Treatment

Participants receive Bevacizumab in combination with microbubble-mediated FUS every 2 weeks up to 34 weeks or until progression

up to 34 weeks

Bi-weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 52 weeks

Regular follow-up visits

Survival Follow-up

Overall survival is monitored via phone interviews every 3 months

up to 24 months

Treatment Details

Interventions

• Bevacizumab
• NaviFUS System

Trial Overview The study is testing the safety and effectiveness of Bevacizumab (BEV), a standard treatment for rGBM, when combined with a new technique using microbubbles and Focused Ultrasound (FUS). This combination aims to improve outcomes for patients.

Bevacizumab is already approved in European Union, United States, Japan, Canada for the following indications:

Approved in European Union as Avastin for:

• Colorectal cancer
• Breast cancer
• Non-small cell lung cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in United States as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Glioblastoma
• Renal cell carcinoma
• Cervical cancer
• Ovarian cancer

Approved in Japan as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in Canada as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Who Is Running the Clinical Trial?

NaviFUS Corporation

Lead Sponsor

Trials

10

Recruited

120+

NaviFUS US LLC

Collaborator

Trials

2

Recruited

20+

Findings from Research

A study of 310 glioblastoma patients from 2010 to 2014 found that the use of bevacizumab did not improve overall survival compared to patients treated before its approval, with median survival remaining similar at 13.5 months for IDH wild-type tumors.

However, patients receiving bevacizumab experienced a significant reduction in corticosteroid use during second-line treatment, suggesting a potential clinical benefit in managing treatment side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab may improve quality of life, but not overall survival in glioblastoma: an epidemiological study. Gramatzki, D., Roth, P., Rushing, EJ., et al.[2020]

Bevacizumab, used to treat glioblastoma and other tumors, has a unique toxicity profile that can lead to serious side effects like gastrointestinal perforation and intracranial hemorrhages, particularly in glioblastoma patients.

The study systematically reviewed these adverse events, identifying risk factors and suggesting preventive and therapeutic measures to reduce treatment-related complications, emphasizing the need for careful monitoring in patients receiving this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practical management of bevacizumab-related toxicities in glioblastoma. Brandes, AA., Bartolotti, M., Tosoni, A., et al.[2022]

Bevacizumab significantly increases the risk of cerebrovascular events, including CNS ischemic events and CNS hemorrhage, with a relative risk of 3.28 based on a meta-analysis of 17 randomized controlled trials involving 12,917 patients.

The risk of cerebrovascular events varies with the dose of bevacizumab and is particularly high in patients with metastatic colorectal cancer, indicating that careful monitoring is needed for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased risk of cerebrovascular events in patients with cancer treated with bevacizumab: a meta-analysis. Zuo, PY., Chen, XL., Liu, YW., et al.[2021]

References

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

Focused Ultrasound Enhances Central Nervous System Delivery of Bevacizumab for Malignant Glioma Treatment. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

From Focused Ultrasound Tumor Ablation to Brain Blood Barrier Opening for High Grade Glioma: A Systematic Review. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Antiangiogenic-targeting drug-loaded microbubbles combined with focused ultrasound for glioma treatment. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Bevacizumab may improve quality of life, but not overall survival in glioblastoma: an epidemiological study. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Focused ultrasound mediated blood-brain barrier opening is safe and feasible in a murine pontine glioma model. [2023]

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

Practical management of bevacizumab-related toxicities in glioblastoma. [2022]

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

Increased risk of cerebrovascular events in patients with cancer treated with bevacizumab: a meta-analysis. [2021]

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

Emerging Therapeutic Strategies for Brain Tumors. [2022]

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

Bevacizumab Use and the Risk of Arterial and Venous Thromboembolism in Patients with High-Grade Gliomas: A Nested Case-Control Study. [2020]

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

Neuronavigation-guided focused ultrasound for transcranial blood-brain barrier opening and immunostimulation in brain tumors. [2022]