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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for individuals with glioblastoma, a type of brain tumor that has returned after initial treatments like surgery and chemotherapy. Researchers aim to determine if using Bevacizumab (also known as Avastin) with focused ultrasound, a type of sound wave therapy, is safe and effective. Candidates for the trial include those whose glioblastoma has recurred after surgery or other treatments, particularly if their tumor is small or mostly removed and they are not currently on certain heart medications. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new therapy combination.

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 prior data suggests that Bevacizumab and the NaviFUS System are safe for treating brain tumors?

Research has shown that using Bevacizumab (BEV) with focused ultrasound (FUS) and microbubbles is safe for treating brain tumors. This method enhances drug delivery to the brain by temporarily opening the blood-brain barrier, a protective layer around the brain. As a result, medication can reach the tumor more easily without causing significant harm.

The focused ultrasound technique is noninvasive, eliminating the need for surgery and reducing potential risks. Patients generally tolerate BEV well when used with this method. Studies have not consistently reported major side effects, indicating that this treatment is relatively safe for patients with recurrent glioblastoma, a type of brain tumor. While any treatment can have side effects, current research supports the safety of this approach. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for brain tumors, which often include surgery, radiation, and traditional chemotherapy, bevacizumab combined with focused ultrasound offers a unique approach. Bevacizumab is an antibody that specifically targets and inhibits a protein called VEGF, which plays a crucial role in the growth of blood vessels that supply the tumor. The addition of focused ultrasound is particularly exciting because it may enhance the delivery of bevacizumab to the tumor site, potentially increasing its effectiveness. Researchers are hopeful that this combo could provide a more targeted attack on brain tumors with fewer side effects compared to conventional therapies.

What evidence suggests that Bevacizumab combined with focused ultrasound is effective for brain tumors?

This trial will investigate the combination of Bevacizumab (BEV) and the NaviFUS system for treating recurring glioblastoma (rGBM), a type of brain cancer. Research has shown that Bevacizumab may help treat rGBM, with one study indicating that 57% of patients experienced noticeable tumor shrinkage. However, long-term survival remains challenging, with only 11% of patients living for four years after treatment. The NaviFUS system uses focused ultrasound to potentially enhance the effects of BEV by accurately targeting brain tumors. Early findings suggest it might help some patients live longer and maintain stable conditions. This combination aims to improve outcomes for those with rGBM. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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+

Published Research Related to This Trial

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5581989/

Clinical Outcomes in Recurrent Glioblastoma with ... Bevacizumab (BEV) is a common treatment for recurrent glioblastoma (GBM). After progression on BEV, there is no consensus on subsequent therapy, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4733960/

Efficacy and safety of bevacizumab for the treatment of ... In addition, 57% of the patients (95% CI, 39–74%) demonstrated at least a partial response (PR), and the 4-year survival rate was demonstrated to be 11% in this ...

3. avastin.com avastin.com/hcp/rgbm/efficacy-data.html

Avastin® (bevacizumab) Clinical Trials | rGBM Treatment Single-agent Avastin outcomes were confirmed in a supportive study conducted by the National Cancer Institute ; Number of patients, 56 ; Primary, Objective ...

4. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-023-11043-6

Use of Bevacizumab in recurrent glioblastoma - BMC Cancer A phase II trial found that BEV plus ONA improved OS in patients with rGBM having unmethylated MGMT (mOS, ONA + BEV vs. PLA + BEV, 10.9 vs. 7.5 ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa1308573

A Randomized Trial of Bevacizumab for Newly Diagnosed ... First-line use of bevacizumab did not improve overall survival in patients with newly diagnosed glioblastoma. Progression-free survival was prolonged.

6. navifus.com navifus.com/2020/03/30/navifus-bevacizumab-clinical-trial-approved/

Combination NaviFUS System and Bevacizumab Clinical ... The NaviFUS System is noninvasive and can greatly reduce the risk of opening the blood-brain barrier (BBB) while simultaneously enhancing drug ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06329570?cond=Brain%20Tumor&term=focused%20ultrasound&aggFilters=status:not%20rec&rank=6

Safety and Efficacy of Bevacizumab in Combination With ... The study aims to demonstrate the high safety profile and effectiveness of BEV+FUS-MB targeted therapy for brain tumors. Any patient with a histological ...

8. mdpi.com mdpi.com/2072-6694/17/3/513

Clinical Trials of Focused Ultrasound for Brain Tumors We found a total of 30 early-stage clinical trials investigating FUS to treat a variety of brain tumors in pediatric patients, as well as adult patients.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT06329570

NCT06329570 | Safety and Efficacy of Bevacizumab in ... The study aims to demonstrate the high safety profile and effectiveness of BEV+FUS-MB targeted therapy for brain tumors. Any patient with a histological ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7327352/

Neuronavigation-guided focused ultrasound (NaviFUS) for ... Blood-brain barrier (BBB) limits over 95% of drugs' penetration into brain, which has been a major obstacle in treating patients with glioblastoma.