Bevacizumab for Brain Cancer

Overseen By John Boockvar, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Northwell Health

Must not be taking: Bevacizumab

Disqualifiers: Pregnancy, Lactation, Significant medical conditions

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: Unknown

Duration: 6 months

54 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of repeated doses of Bevacizumab (also known as Avastin) for treating aggressive brain tumors like glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA). Researchers aim to determine if administering this drug directly into the brain’s blood supply can extend patients' lives and improve their well-being. Individuals with a confirmed diagnosis of recurrent or resistant GBM or AA, who have not received more than two previous infusions of Bevacizumab, may qualify for this trial. As a Phase 1, Phase 2 trial, this research seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking advancements in brain tumor treatment.

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

The trial protocol does not specify if you need to stop your current medications. Please consult with the trial coordinators for more details.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that bevacizumab, a treatment for certain brain tumors, has been studied for its safety in people. In earlier studies, some risks were linked to bevacizumab. For instance, serious blood clots occurred in 5% of patients who received the treatment with chemotherapy, compared to 2% of those who did not. Additionally, reports indicated over 3,000 different side effects in patients.

However, bevacizumab is already used for other conditions, suggesting some known safety. Studies on brain tumors indicate that while there are risks, bevacizumab is often used because it can help delay disease progression.

Overall, the treatment presents both benefits and risks, and deciding to join a trial should involve considering both aspects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Bevacizumab is unique because it targets the blood vessels that supply nutrients to brain tumors, essentially starving the cancer cells. Unlike traditional chemotherapy, which attacks rapidly dividing cells indiscriminately, Bevacizumab specifically inhibits a protein called VEGF (vascular endothelial growth factor), which plays a key role in tumor angiogenesis — the process of new blood vessel formation. Researchers are excited about Bevacizumab because it offers a more targeted approach, potentially reducing side effects and improving outcomes for patients with brain cancer.

What evidence suggests that Bevacizumab might be an effective treatment for brain cancer?

Research has shown that Bevacizumab can help treat recurrent glioblastoma, an aggressive brain cancer. In a study of 995 patients, those who received Bevacizumab lived without their cancer worsening for about 4.2 months, and their overall survival improved after treatment. Another study found that 57% of patients experienced at least some reduction in tumor size. The 4-year survival rate for these patients was 11%, which is significant given the disease's aggressiveness. In this trial, participants will receive Bevacizumab in different experimental arms. These findings suggest that Bevacizumab is a promising option for people with recurring brain tumors. ^{1 6 7 8 9}

Who Is on the Research Team?

John Boockvar, MD

Principal Investigator

Feinstein Institute for Medical Research

Are You a Good Fit for This Trial?

Adults with relapsed or refractory high-grade brain tumors like GBM and AA, who have not had more than two cycles of Bevacizumab treatment. Participants must be able to perform daily activities (Karnofsky performance status ≥70%), have at least one confirmed tumor site, and agree to use contraception during the study.

Inclusion Criteria

I have a confirmed diagnosis of a specific type of brain tumor that has returned or is not responding to treatment.

I am mostly independent and can care for myself.

I have at least one tumor confirmed by biopsy.

Exclusion Criteria

Patients with significant inter-current medical or psychiatric conditions that would place them at increased risk or affect their ability to receive or comply with treatment or post-treatment clinical monitoring

I have received more than 2 cycles of Bevacizumab at 10mg/kg.

I am not pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive repeated intraarterial delivery (SIACI) of Bevacizumab, with one arm also receiving biweekly IV Bevacizumab. IA therapy is repeated upon MRI progression.

6 months

Biweekly visits for IV therapy, additional visits for IA therapy as needed

Follow-up

Participants are monitored for safety and effectiveness after treatment, including progression-free survival and overall survival assessments.

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab

Trial Overview The trial is testing repeated doses of intraarterial Bevacizumab for safety and effectiveness in treating recurrent malignant glioma. It aims to see if this method improves survival compared to standard intravenous therapy by delivering the drug directly into arteries supplying the tumor.

How Is the Trial Designed?

Group I: Arm 2 Experimental Treatment 1 Intervention

Group II: Arm 1 Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Northwell Health

Lead Sponsor

Trials

481

Recruited

470,000+

Feinstein Institute for Medical Research

Collaborator

Trials

22

Recruited

5,700+

Published Research Related to This Trial

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 (Avastin) received accelerated FDA approval for treating glioblastoma multiforme (GBM) based on its ability to produce partial responses in 25.9% of patients in one trial and 19.6% in another, with median response durations of approximately 4.2 and 3.9 months, respectively.

While bevacizumab shows efficacy in GBM treatment, it is associated with significant adverse events, including serious risks like CNS hemorrhage and thromboembolic events, highlighting the need for careful patient monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA drug approval summary: bevacizumab (Avastin) as treatment of recurrent glioblastoma multiforme. Cohen, MH., Shen, YL., Keegan, P., et al.[2022]

Inhibiting vascular endothelial growth factor (VEGF) with agents like bevacizumab is intended to normalize tumor blood vessels, potentially improving drug delivery and radiotherapy effectiveness for primary CNS tumors.

However, concerns have emerged that these agents may restore the blood-brain barrier's low permeability too quickly, which could reduce the effectiveness of standard treatments like radiochemotherapy and increase tumor infiltration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The paradoxical effect of bevacizumab in the therapy of malignant gliomas. Thompson, EM., Frenkel, EP., Neuwelt, EA.[2021]

Bevacizumab, an anti-VEGF therapy, may not be effective against brain metastases from non-small cell lung carcinoma (NSCLC) due to their significantly higher proportion of mature blood vessels compared to primary tumors, which suggests resistance to this treatment.

The study found that while hypoxia markers were similar between primary tumors and brain metastases, other factors like VEGF expression and microvessel density differed, indicating that brain metastases may not respond to anti-angiogenic therapies in the same way as the original tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vascular phenotypes in primary non-small cell lung carcinomas and matched brain metastases. Jubb, AM., Cesario, A., Ferguson, M., et al.[2021]

In a retrospective analysis of the AVAglio trial involving 921 glioblastoma patients, those with IDH1 wild-type proneural tumors showed a significant overall survival (OS) benefit from bevacizumab treatment compared to placebo, with an OS of 17.1 months versus 12.8 months.

While patients with mesenchymal and proneural tumors experienced progression-free survival (PFS) benefits from bevacizumab, only the proneural subtype demonstrated a corresponding OS advantage, highlighting the importance of molecular subtypes in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patients With Proneural Glioblastoma May Derive Overall Survival Benefit From the Addition of Bevacizumab to First-Line Radiotherapy and Temozolomide: Retrospective Analysis of the AVAglio Trial. Sandmann, T., Bourgon, R., Garcia, J., et al.[2022]

In a study of 48 patients with recurrent glioblastoma, single-agent bevacizumab demonstrated significant biological activity, with 71% of patients achieving a radiographic response and a median progression-free survival of 16 weeks.

However, the combination of bevacizumab with irinotecan showed no objective responses, highlighting that while bevacizumab is effective as a standalone treatment, its efficacy may not extend when combined with certain other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. Kreisl, TN., Kim, L., Moore, K., et al.[2022]

Bevacizumab (BEV) has shown a median radiographic response rate of 25% and a 6-month progression-free survival (PFS6) rate of 40% in patients with recurrent glioblastoma, leading to its accelerated approval in the USA for this indication.

Despite improvements in treatment options, glioblastoma remains a challenging and incurable condition, with current therapies yielding low response rates and variable survival outcomes, highlighting the need for ongoing research into effective treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab for the treatment of glioblastoma. Chowdhary, S., Chamberlain, M.[2022]

In a study of 12 patients with relapsed/refractory brain tumors treated with a combination of bevacizumab and irinotecan, the treatment showed promising results with two complete responses and two partial responses after three months, along with a median progression-free survival of 11 months.

The treatment was well tolerated, with low toxicity reported, and 42% of patients remained progression-free at two years, indicating that this regimen could be a viable option for managing difficult-to-treat brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab-containing regimen in relapsed/progressed brain tumors: a single-institution experience. Schiavetti, A., Varrasso, G., Mollace, MG., et al.[2020]

In a phase III trial involving 911 patients with newly diagnosed glioblastoma, those treated with bevacizumab had a longer safety follow-up (12.3 months) and a higher completion rate of maintenance temozolomide (64.6%) compared to placebo (36.9%).

While bevacizumab was associated with a higher incidence of adverse events such as arterial thromboembolic events (5.9% vs 1.6%) and wound-healing complications (6.9% vs 4.7%), these did not hinder patients' ability to receive standard treatment or undergo subsequent surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab, temozolomide, and radiotherapy for newly diagnosed glioblastoma: comprehensive safety results during and after first-line therapy. Saran, F., Chinot, OL., Henriksson, R., 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]

In a phase II trial involving 115 patients with non-small-cell lung cancer (NSCLC) and treated brain metastases, the addition of bevacizumab to chemotherapy or erlotinib showed a low incidence of serious CNS hemorrhage, with no cases of grade 2 or higher reported among 106 safety-evaluable patients.

The study suggests that bevacizumab is safe for use in this patient population, as it was well-tolerated with a median treatment duration of 6.3 months and only a small percentage of patients (24.5%) discontinuing due to adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of bevacizumab in patients with non-small-cell lung cancer and brain metastases. Socinski, MA., Langer, CJ., Huang, JE., et al.[2022]

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 ... A previous review (995 patients) estimated a progression free survival (PFS) on BEV of 4.2 months (SD±2.1) with an overall survival (OS) after progression on ...

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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 ...

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Avastin® (bevacizumab) Clinical Trials | rGBM Treatment Single-agent Avastin outcomes were confirmed in a supportive study conducted by the National Cancer Institute ; Primary, Objective response rate · 19.6%, 10.9– ...

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A systematic review and external pseudodata-based analysis In this study, we conducted an external control-based reassessment of the bevacizumab efficacy in newly diagnosed GBM (ndGBM) against the standard Stupp ...

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Benefits and Risks of Treatment for recurrent gliobastoma ... Serious to life threatening blood clots in the veins of the body were seen in 5% of patients receiving Avastin with chemotherapy compared to 2% of patients ...

7. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1595642/full

Comparative safety analysis of bevacizumab and alkylating ... Results: In the context of glioblastoma treatment, 3,323 adverse reports were associated with bevacizumab, 5,283 with temozolomide, and 427 with ...

8. ascopubs.org ascopubs.org/doi/10.1200/jco.2010.28.15_suppl.2008

Updated safety and survival of patients with relapsed ... Results: Median OS at last follow-up (15 July 2009) was 9.3 mo (95% CI 8.2–11.8) in the BV arm and 8.9 mo (95% CI 7.9–11.9) in the BV+IR arm.

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0967586819321721

Impact of adverse events of bevacizumab on survival ... Our results indicate that the development of AEs to bevacizumab or bevacizumab-containing regimens is associated with unfavorable glioma-related survival ...