Electric Field Therapy + Bevacizumab for Meningioma

Recruiting at 6 trial locations

Overseen By Study Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Northwestern University

Must not be taking: Bevacizumab, Immunosuppressants, others

Disqualifiers: Infratentorial disease, Hypertension, Stroke, others

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

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

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

Compensation: Varies

Number of Visits: 5

Duration: 6 months

27 Participants Needed

Trial Summary

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

The trial requires a 4-week period without taking any systemic treatments before joining. You cannot take other investigational drugs or anti-cancer therapies during the trial.

What data supports the effectiveness of the drug Bevacizumab for treating meningioma?

Research suggests that Bevacizumab, which blocks a protein that helps tumors grow blood vessels, may help shrink meningiomas (a type of brain tumor) and reduce swelling around them, especially in more aggressive cases. This is based on findings from studies on patients with difficult-to-treat meningiomas. ^{1 2 3 4 5}

Is Electric Field Therapy + Bevacizumab safe for treating meningioma?

Bevacizumab, used in combination with other treatments, has been generally safe for patients with meningioma, with most side effects being mild, such as minor bleeding, nausea, and diarrhea. Serious side effects were rare, but included intestinal perforation and central nervous system bleeding in isolated cases. ^{2 3 6 7 8}

How is the treatment with Electric Field Therapy and Bevacizumab unique for meningioma?

This treatment combines Bevacizumab, which targets blood vessel growth in tumors, with Electric Field Therapy, which disrupts cancer cell division. This dual approach is novel for meningioma, especially for cases that do not respond to surgery or radiation. ^{1 3 4 9 10}

What is the purpose of this trial?

The purpose of this research study is to determine the effects bevacizumab (the study drug) combined with Optune (the study device) tumor treatment field therapy has on meningiomas. Bevacizumab is considered investigational because the US Food and Drug Administration (FDA) has not approved its use for the treatment of meningiomas. The study drug is a medication that blocks the growth of new blood vessels. It is thought that the study drug may interfere with the growth of new blood vessels and therefore might stop tumor growth, and possibly shrink the tumor by keeping it from receiving nutrients and oxygen supplied by the blood vessels. Optune is also considered investigational because the US FDA has not approved its use for the treatment of meningiomas. Optune is a device that the patient will wear and use for at least 18 hours of each day. It delivers alternating electrical current to the patient's brain tumor and by doing so interrupts a process called mitosis. Mitosis needs to occur in order for cell division to occur and allows tumors to grow. By slowing this process, we hypothesize that meningioma growth may also be slowed.

Research Team

Priya U. Kumthekar

Principal Investigator

Northwestern University

Eligibility Criteria

This trial is for adults with Grade 2 or 3 meningioma that has come back or gotten worse after standard treatments, including surgery and radiation. They must have a life expectancy of at least 12 weeks, be able to perform daily activities (Karnofsky performance status >=60%), and have good organ function. Women who can get pregnant and men with partners who can get pregnant must use birth control. People can't join if they've had recent surgeries, are on certain other treatments, have specific medical devices implanted, are sensitive to hydrogels, have uncontrolled blood pressure or bleeding disorders, or are pregnant/nursing.

Inclusion Criteria

You are expected to live for at least 12 more weeks.

If you are capable of becoming pregnant, you need to have a recent negative pregnancy test before joining the study.

Patients must be able to comply with all protocol requirements

Exclusion Criteria

My cancer affects the lower part of my brain or spine.

I have been treated with bevacizumab before.

I have not had a stroke or mini-stroke in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive bevacizumab intravenously and undergo electric field therapy using Optune daily over 18 hours. Courses repeat every 28 days.

6 months

Visits every 2 weeks for IV treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 3 months for 2 years.

24 months

Follow-up visits every 3 months

Treatment Details

Interventions

• Bevacizumab
• NovoTTF-200A Device

Trial Overview The study tests the combination of Bevacizumab (a drug blocking new blood vessel growth) and Optune (a device delivering electric fields to the brain) in treating recurrent/progressive meningiomas. Bevacizumab isn't FDA-approved for this cancer type yet; it aims to starve tumors by cutting off their blood supply. Optune is worn daily for at least 18 hours and disrupts tumor cell division.

Participant Groups

Group I: Treatment (bevacizumab, electric field therapy) Experimental Treatment 4 Interventions

Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 of courses 1-4. Beginning on day 1 of course 5, patients may choose to receive bevacizumab IV every 3 weeks or remain on the every 2-week schedule. Patients also undergo electric field therapy using Optune (formerly NovoTTF-200A System) daily over 18 hours. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

NovoCure Ltd.

Industry Sponsor

Trials

64

Recruited

6,100+

Ashley Cordova

NovoCure Ltd.

Chief Executive Officer

Bachelor of Science in Material Engineering from Ben-Gurion University of the Negev, Israel

Uri Weinberg

NovoCure Ltd.

Chief Medical Officer since 2020

MD from an unspecified institution

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 7 NF2 patients receiving bevacizumab, 36% of meningiomas showed a decrease in size, indicating that this treatment may help slow or reverse the growth of NF-related meningiomas.

Despite some positive effects, there is a significant risk of side effects, including a previously reported fatal case of intracerebral hemorrhage, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of bevacizumab on intracranial meningiomas in patients with neurofibromatosis type 2 - a retrospective case series. Alanin, MC., Klausen, C., Caye-Thomasen, P., et al.[2019]

Bevacizumab showed some potential as a palliative treatment for aggressive pituitary adenomas in three patients who had exhausted standard therapies, with one patient experiencing disease stabilization for 18 months.

Despite some initial positive responses, the overall effectiveness of bevacizumab remains uncertain due to the advanced disease stage of the patients and the limited duration of treatment, highlighting the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab in Aggressive Pituitary Adenomas - Experience with 3 Patients. Osterhage, K., Rotermund, R., Droste, M., et al.[2021]

Bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, shows promise in treating refractory meningioma, leading to both reduction in brain edema and actual tumor shrinkage, particularly in patients with higher-grade tumors (WHO grades II-III).

The review highlights the importance of the VEGF pathway in meningioma angiogenesis and suggests that further research into anti-VEGF therapies could provide effective treatment options for patients with relapsed or metastatic meningioma who have not responded to surgery or radiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic therapy for relapsed/refractory meningioma: Is there potential for antiangiogenic agents? Dasanu, CA., Samara, Y., Codreanu, I., et al.[2019]

Bevacizumab and imatinib effectively reduced meningioma-induced neovascularization in a rat corneal angiogenesis assay, indicating their potential as antiangiogenic treatments.

The study suggests that targeting angiogenic pathways in meningiomas with these drugs could improve patient prognosis by suppressing tumor-induced blood vessel formation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiangiogenic Molecules Suppressed Meningioma-Induced Neovascularization: A Corneal Angiogenesis Study. Tatarli, N., Ceylan, D., Oksal, MD., et al.[2022]

Bevacizumab, an anti-angiogenic agent, shows promise in improving progression-free survival (PFS) in patients with treatment-refractory meningiomas, with a median PFS of 16.8 months based on a review of 92 patients across 11 studies.

The study highlights the need for larger randomized controlled trials to further evaluate the overall survival benefits and safety of bevacizumab in treating recurrent or progressive meningiomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of bevacizumab for treatment-refractory meningiomas: A systematic analysis and literature review. Franke, AJ., Skelton, WP., Woody, LE., et al.[2023]

In a phase II trial involving 17 patients with recurrent meningioma, the combination of everolimus and bevacizumab resulted in stable disease for 88% of participants, with a median progression-free survival (PFS) of 22 months, indicating promising efficacy for this treatment in challenging cases.

The treatment was generally well-tolerated, with only four patients experiencing significant toxicity, suggesting that this combination therapy could be a viable option for patients with limited chemotherapy alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of bevacizumab and everolimus as treatment for patients with refractory, progressive intracranial meningioma. Shih, KC., Chowdhary, S., Rosenblatt, P., et al.[2022]

In a study of 10 patients (ages 14 to 70) treated with antiangiogenic agents like bevacizumab and pazopanib for vestibular schwannomas and meningiomas, the treatment showed safety with only minor side effects and no severe toxicities.

Some patients experienced positive outcomes, such as stable or improved disease status, particularly in those with neurofibromatosis type 2 (NF2), suggesting that antiangiogenic agents may be effective in managing nonmalignant brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiangiogenic agents for nonmalignant brain tumors. Hawasli, AH., Rubin, JB., Tran, DD., et al.[2022]

In a study of 14 patients with recurrent meningiomas treated with bevacizumab, 86% experienced progression-free survival at 6 months, indicating promising efficacy regardless of tumor grade or treatment combination.

Bevacizumab was generally safe, with most side effects being mild, although there were instances of serious complications like CNS hemorrhage and intestinal perforation, suggesting careful monitoring is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab therapy for adults with recurrent/progressive meningioma: a retrospective series. Lou, E., Sumrall, AL., Turner, S., et al.[2022]

Bevacizumab, a monoclonal antibody targeting VEGF-A, has shown promise in treating recurrent high-grade meningiomas, as demonstrated by a patient who experienced significant visual field recovery after 3 cycles of treatment.

High-grade meningiomas are more aggressive and have a higher tendency to recur compared to lower-grade tumors, making effective treatment options like bevacizumab crucial for improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement in Visual Fields After Treatment of Intracranial Meningioma With Bevacizumab. Ly, KI., Hamilton, SR., Rostomily, RC., et al.[2015]

Bevacizumab has shown some effectiveness in managing recurrent meningiomas, particularly in cases that are multifocal or near critical structures, suggesting it could be a valuable treatment option.

The search for new systemic therapies, including targeted therapies and immunotherapy, is ongoing, but there is caution due to past failures in treating central nervous system diseases and challenges in trial development for these slow-growing tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multimodality Therapy of Patients with Refractory Meningiomas. Ahmad, H., Schiff, D.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Effect of bevacizumab on intracranial meningiomas in patients with neurofibromatosis type 2 - a retrospective case series. [2019]

2. Germany pubmed.ncbi.nlm.nih.gov

Bevacizumab in Aggressive Pituitary Adenomas - Experience with 3 Patients. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Systemic therapy for relapsed/refractory meningioma: Is there potential for antiangiogenic agents? [2019]

4. Turkey pubmed.ncbi.nlm.nih.gov

Antiangiogenic Molecules Suppressed Meningioma-Induced Neovascularization: A Corneal Angiogenesis Study. [2022]

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

Role of bevacizumab for treatment-refractory meningiomas: A systematic analysis and literature review. [2023]

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

A phase II trial of bevacizumab and everolimus as treatment for patients with refractory, progressive intracranial meningioma. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Antiangiogenic agents for nonmalignant brain tumors. [2022]

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

Bevacizumab therapy for adults with recurrent/progressive meningioma: a retrospective series. [2022]

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

Improvement in Visual Fields After Treatment of Intracranial Meningioma With Bevacizumab. [2015]

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

Multimodality Therapy of Patients with Refractory Meningiomas. [2020]