Bevacizumab for Glioblastoma

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Global Neurosciences Institute

Disqualifiers: Pregnancy, Lactation, Significant medical conditions

No Placebo Group

Breakthrough Therapy

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

The high-grade malignant brain tumor glioblastoma multiforme (GBM) comprise the majority of all primary brain tumors in adults. This group of tumors also exhibits the most aggressive behavior, resulting in median overall survival durations of only 9-12 months for GBM. Initial therapy consists of surgical resection, external beam radiation or both. Currently, all patients experience a recurrence after this first-line therapy, so improvements in both first-line and salvage therapy are critical to enhancing quality-of-life and prolonging survival. Superselective Intraarterial Cerebral Infusion (SIACI) is a technique that can effectively increase the concentration of drug delivered to the brain while sparing the body of systemic side effects. This technique threads a tiny catheter through the patient's femoral artery in the leg, up through the body and neck and into the brain. Once the catheter reaches the brain, chemotherapy is released to the blood vessels that feed the tumor.

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 data supports the effectiveness of the drug Bevacizumab (Avastin) for treating glioblastoma?

Research shows that Bevacizumab may improve the quality of life for glioblastoma patients and can help delay the progression of the disease, although it does not significantly extend overall survival. Some studies suggest that certain subgroups of patients might benefit more from this drug when combined with other treatments. ^{1 2 3 4 5}

Is Bevacizumab safe for treating glioblastoma?

Bevacizumab, also known as Avastin, has been linked to some serious side effects like stroke, bleeding, and wound-healing problems, especially in glioblastoma patients. These side effects can be life-threatening, so it's important to identify risk factors and manage them carefully. ^{1 4 6 7 8}

How is the drug Bevacizumab different from other treatments for glioblastoma?

Bevacizumab (Avastin) is unique because it targets and binds to a protein called VEGF, which helps tumors form new blood vessels. By blocking this protein, Bevacizumab reduces tumor growth and brain swelling, potentially improving quality of life, although it does not extend overall survival for most patients. ^{1 2 7 9 10}

Research Team

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• Bevacizumab (Monoclonal Antibodies)

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.

Participant Groups

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 Japan, Canada for the following indications:

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+

Findings from Research

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]

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, 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]

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]

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 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 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 (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]

References

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

Bevacizumab may improve quality of life, but not overall survival in glioblastoma: an epidemiological study. [2020]

2. United States 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. [2022]

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

Bevacizumab and chemotherapy for recurrent glioblastoma: a single-institution experience. [2022]

4. England pubmed.ncbi.nlm.nih.gov

The future of antiangiogenic treatment in glioblastoma. [2015]

5. England 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. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Practical management of bevacizumab-related toxicities in glioblastoma. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Bevacizumab, temozolomide, and radiotherapy for newly diagnosed glioblastoma: comprehensive safety results during and after first-line therapy. [2022]

8. England 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. [2020]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Bevacizumab for glioblastoma. [2022]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Role of bevacizumab therapy in the management of glioblastoma. [2021]