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

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to evaluate how bevacizumab (Avastin), combined with the Optune device (NovoTTF-200A Device), affects meningiomas, a type of brain tumor. Bevacizumab may inhibit tumor growth by cutting off its blood supply, while Optune uses electric fields to slow cell division in the tumor. This trial targets individuals whose meningioma has recurred after standard treatments, such as surgery and radiation. Participants should have previously tried other therapies but not bevacizumab, and must have a specific type of tumor growth confirmed by scans like MRI or CT. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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 prior data suggests that this combination of bevacizumab and Optune is safe for treating meningiomas?

Research has shown that bevacizumab is usually well-tolerated by patients with meningiomas, a type of brain tumor. In studies, about 86% of patients did not experience disease progression for at least six months. Some side effects occurred, but they were manageable and did not cause serious problems for most patients.

Regarding the Optune device, studies indicate it is generally safe. Patients using this device for brain tumors did not encounter any new or unexpected safety issues, suggesting it does not cause severe side effects.

Both treatments have shown promise in previous studies and are considered safe for many patients. However, individual experiences can vary, so discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Bevacizumab and electric field therapy for treating meningioma because it offers a novel approach compared to conventional treatments like surgery, radiation, and chemotherapy. Bevacizumab is an antibody that blocks blood vessel growth in tumors, cutting off their nutrient supply, while electric field therapy uses the Optune device to disrupt cancer cell division with electric fields. This dual method not only targets the tumor's blood supply but also directly interferes with the cancer cells' ability to multiply, offering a potentially more comprehensive attack on the tumor. This innovative combination could lead to improved outcomes for patients with meningioma by addressing the disease on multiple fronts.

What evidence suggests that this combination of bevacizumab and electric field therapy might be effective for meningioma?

Research has shown that bevacizumab can help keep meningiomas stable. Meningiomas are tumors that form in the protective layers around the brain and spinal cord. Some studies found that about 73% of patients had tumors that did not grow for over a year after receiving this treatment. Bevacizumab stops the growth of blood vessels, cutting off the tumor's supply of nutrients and oxygen. In this trial, participants will receive bevacizumab alongside Optune, a device that uses electric fields to target the tumor. Optune has been linked to better survival rates in brain tumor patients by slowing down how quickly tumor cells divide. Together, these treatments aim to stop or slow the growth of meningiomas. ^{1 2 6 7 8}

Who Is on the Research Team?

Priya U. Kumthekar

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

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.

Patients must be able to comply with all protocol requirements

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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, 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 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]

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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6057170/

Role of bevacizumab for treatment-refractory meningiomas Results analyzed from the studies (61 patients) demonstrated median overall PFS of 16.8 months (range: 6.5-22 months) and that 73% of patients were progression ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9364983/

Efficacy of Bevacizumab in High-Grade Meningiomas This study retrospectively analyzed the clinical data of 139 patients and demonstrated that BV could improve PFS and OS at 12 and 36 months ...

3. academic.oup.com academic.oup.com/noa/article/6/1/vdae128/7732110

Effect of bevacizumab on refractory meningiomas: 3D ... Bevacizumab was shown to be effective by both assessment methods. According to RANO criteria, the rate of progression-free survival at 6 months ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01125046

Bevacizumab in Treating Patients With Recurrent or ... PURPOSE: This phase II trial is studying how well bevacizumab works in treating patients with recurrent or progression meningiomas. Detailed Description.

5. ascopubs.org ascopubs.org/doi/10.1200/jco.2015.33.15_suppl.2055

Phase II trial of bevacizumab in patients with surgery and ... Conclusions: Treatment of progressive meningioma with BEV commonly leads to disease stabilization. The results are promising compared to a ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3404217/

Bevacizumab therapy for adults with recurrent/progressive ... Progression-free survival at 6 months was 86 % and was comparable regardless of meningioma grade and whether bevacizumab was administered as monotherapy or in ...

7. academic.oup.com academic.oup.com/noa/article/4/1/vdac123/6672581

A multi-institutional phase II trial of bevacizumab for recurrent ... The study results suggest BEV is an active agent and should be considered for use in patients with refractory meningiomas. The current study ...

8. redjournal.org redjournal.org/article/S0360-3016(15)01544-8/fulltext

Outcomes for Patients With Intracranial Meningiomas ... Mean overall survival from diagnosis was 234 months. Mean overall survival after initiation of bevacizumab treatment and after first radiation treatment for ...