Bevacizumab for Glioblastoma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Global Neurosciences Institute

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: 3

Duration: Varies based on individual response

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to deliver the drug bevacizumab (Avastin) directly to the brain for treating glioblastoma, an aggressive brain cancer. Using Superselective Intraarterial Cerebral Infusion, a special catheter technique, doctors aim to deliver more of the drug to the tumor while reducing side effects on the rest of the body. This trial may suit individuals with a confirmed diagnosis of recurrent glioblastoma after surgery. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking medical advancements.

Will I have to stop taking my current medications?

The trial requires that you stop any IV chemotherapy for three weeks and any external beam radiation for four weeks before starting the treatment. The protocol does not specify about other medications, so it's best to discuss your current medications with the trial team.

What prior data suggests that this technique is safe for delivering Bevacizumab to the brain?

Research has shown that delivering Bevacizumab directly into the brain's blood vessels is safe for treating recurring aggressive brain tumors, such as glioblastoma. Earlier studies found that this method did not cause major side effects or treatment-related deaths.

One study demonstrated that using Bevacizumab in this manner was both safe and effective for patients with recurring glioblastoma. Another study confirmed that this treatment improved survival rates without causing severe side effects.

These findings suggest that delivering Bevacizumab directly into the brain's blood vessels is well-tolerated by patients, offering a safer option for those with aggressive brain tumors like glioblastoma. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for glioblastoma, which often include surgery, radiation, and oral chemotherapy, Bevacizumab offers a unique approach by targeting blood vessel growth within the tumor. This treatment is administered directly into the arteries, which could potentially deliver the drug more effectively to the tumor site. Researchers are excited because this method of delivery might enhance the drug's effectiveness and reduce side effects compared to traditional intravenous methods.

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

This trial will investigate the use of intra-arterial bevacizumab for glioblastoma. Studies have shown that bevacizumab effectively stops the growth of new blood vessels, which is crucial for slowing tumor growth. Past research on recurring glioblastoma found that delivering bevacizumab directly into the arteries was safe and showed promising results. Specifically, patients treated this way experienced longer periods without cancer progression. This method also targets the drug directly to the brain, potentially reducing side effects in other parts of the body. These findings suggest that using bevacizumab in this manner could be a promising option for treating glioblastoma. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

Adults over 18 with a specific brain cancer called Glioblastoma Multiforme that has come back after surgery can join. They should be in good enough health to understand the study and give consent, have normal blood clotting, not have had recent chemotherapy or radiation, and agree to use birth control.

Inclusion Criteria

Pre-enrollment coagulation parameters (PT and PTT) must be adequate

Patients must be able to understand and give written informed consent. Informed consent must be obtained at the time of patient screening

I haven't had IV chemotherapy in the last 3 weeks or radiation in the last 4 weeks.

Exclusion Criteria

Women of childbearing potential and fertile men will be informed as to the potential risk of procreation while participating in this research trial and will be advised that they must use effective contraception during and for a period of three months after the treatment period

I am not pregnant or breastfeeding.

Patients with significant intercurrent 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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive repeated intra-arterial bevacizumab injections at 15 mg/kg every 3 weeks

Varies based on individual response

Injections every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab

Trial Overview

The trial is testing Bevacizumab delivered directly to the brain tumor through an artery. This method aims to increase drug concentration at the tumor site while reducing whole-body side effects by using a catheter from the leg artery up into the brain.

How Is the Trial Designed?

Group I: Intra Arterial Bevacizumab Experimental Treatment 1 Intervention

Repeated Intra Arterial bevacizumab injections at 15 mg/kg every 3 weeks

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?

Global Neurosciences Institute

Lead Sponsor

Trials

3

Recruited

140+

Published Research Related to This Trial

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]

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 retrospective analysis of 123 patients with recurrent glioblastoma, those treated with bevacizumab showed significant improvements in both progression-free survival (PFS) and overall survival (OS) compared to a control group.

Older patients (55 years and above) and those with poorer performance status benefited the most from bevacizumab treatment, suggesting that age-related biological differences in glioblastoma may influence treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab and chemotherapy for recurrent glioblastoma: a single-institution experience. Nghiemphu, PL., Liu, W., Lee, Y., et al.[2022]

Bevacizumab (BV) can promote tumor regression and reduce cerebral edema in glioblastoma patients, improving their performance status, although it does not extend overall survival time.

Despite its benefits, BV is associated with adverse events, primarily hypertension and proteinuria, which need to be carefully explained to patients, especially since many present with advanced neurologic symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab for glioblastoma. Narita, Y.[2022]

Bevacizumab, a monoclonal antibody that targets VEGF, has been shown to reduce tumor growth and associated brain swelling in glioblastoma patients, potentially improving their quality of life and survival rates.

Despite its benefits, the review highlights the importance of understanding the potential side effects and complications of bevacizumab, as well as exploring new drug combinations to enhance its efficacy in treating glioblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of bevacizumab therapy in the management of glioblastoma. Peak, SJ., Levin, VA.[2021]

Bevacizumab significantly improves progression-free survival (PFS) in glioblastoma patients, both in first-line and second-line treatments, but does not extend overall survival (OS).

The use of bevacizumab is associated with increased risks of hypertension, proteinuria, thromboembolic events, and infections, highlighting the need for careful monitoring of blood pressure during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Bevacizumab for Treating Glioblastoma: A Systematic Review and Meta-Analysis of Phase II and III Randomized Controlled Trials. Xie, X., Bao, S., Zhao, H., et al.[2023]

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]

In a phase II trial involving 296 patients with recurrent glioblastoma, continuing treatment with bevacizumab (BEV) after first-line therapy did not show a survival benefit compared to placebo, with median survival times of 6.4 months for BEV and 5.5 months for placebo.

The study found no new safety concerns with BEV treatment, as the incidence of severe treatment-related adverse events was similar between the BEV and placebo groups (19% vs. 15%), indicating that BEV can be safely administered through multiple lines of therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Phase II Trial (TAMIGA) Evaluating the Efficacy and Safety of Continuous Bevacizumab Through Multiple Lines of Treatment for Recurrent Glioblastoma. Brandes, AA., Gil-Gil, M., Saran, F., et al.[2020]

Bevacizumab, a monoclonal antibody targeting VEGF, shows a meaningful increase in progression-free survival for newly diagnosed glioblastoma patients, but it does not improve overall survival, highlighting the need for further research.

In recurrent glioblastoma patients, while bevacizumab has shown improved radiographic response and progression-free survival in uncontrolled trials, its effect on overall survival is still being evaluated in an ongoing randomized phase III trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The future of antiangiogenic treatment in glioblastoma. Chinot, OL., Reardon, DA.[2015]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3743246/

Intra-Arterial Delivery of Bevacizumab after Blood-Brain ...

Overall, our data indicate that a single treatment with SIACI BV after BBBD followed by IV BV shows promising results for PFS and comparable results for OS when ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01269853

Study Details | NCT01269853 | Repeated Super-selective ...

A single Super-selective Intraarterial Cerebral Infusion (SIACI) of Bevacizumab (up to 15mg/kg) is safe and effective in the treatment of recurrent GBM.

3.

sciencedirect.com

sciencedirect.com/science/article/pii/S0150986125001099

Efficacy and safety of intra-arterial chemoperfusion as ...

Patients who are diagnosed with glioblastoma have a median overall survival (OS) of 15.5 months if total resection was performed and 5.9 months without.

4.

frontiersin.org

frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.950167/full

A systematic review on intra-arterial cerebral infusions of ...

Results coming from studies, as well as clinical series, have shown that bevacizumab effectively inhibits the formation of new blood vessels and affects the ...

5.

jnis.bmj.com

jnis.bmj.com/content/early/2024/07/30/jnis-2024-021789.full.pdf

arterial carboplatin and bevacizumab in the C6 rat glioma ...

Utilizing our previously developed rat glioma model of. GBM with endovascular access, we now aim to analyze the efficacy of intra- arterial (IA).

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6088330/

Use of bevacizumab in recurrent glioblastoma - PMC

Phase II clinical trials utilizing bevacizumab-containing regimens improved 6-month progression-free survival to 42.6–50.3% in comparison to historical Phase II ...

7.

jnis.bmj.com

jnis.bmj.com/content/16/11/1152

Safety and feasibility of intra-arterial delivery of teniposide to ...

27 These findings indicated that superselective arterial infusion of teniposide might be effective and safe in glioma patients. In conclusion, this small series ...