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}

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 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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

NCT02285959 Philadelphia, PA

Who Is Running the Clinical Trial?

Global Neurosciences Institute Lead Sponsor

References

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

Bevacizumab may improve quality of life, but not overall survival in glioblastoma: an epidemiological study. [2020] The vascular endothelial growth factor antibody bevacizumab (Avastin®), received approval for the treatment of recurrent glioblastoma in many countries including the USA and Switzerland, but not the European Union, in 2009. Here, we explored the hypothesis that the approval of bevacizumab improved outcome with glioblastoma on a population level.

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] The AVAglio (Avastin in Glioblastoma) and RTOG-0825 randomized, placebo-controlled phase III trials in newly diagnosed glioblastoma reported prolonged progression-free survival (PFS), but not overall survival (OS), with the addition of bevacizumab to radiotherapy plus temozolomide. To establish whether certain patient subgroups derived an OS benefit from the addition of bevacizumab to first-line standard-of-care therapy, AVAglio patients were retrospectively evaluated for molecular subtype, and bevacizumab efficacy was assessed for each patient subgroup.

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

Bevacizumab and chemotherapy for recurrent glioblastoma: a single-institution experience. [2022] Bevacizumab has been shown to be effective in the treatment of recurrent glioblastoma in combination with chemotherapy compared with historic controls but not in randomized trials.

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

The future of antiangiogenic treatment in glioblastoma. [2015] A major recent clinical research focus for glioblastoma has been the therapeutic evaluation of antiangiogenic agents. Several vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors and a soluble decoy VEGF receptor have demonstrated nominal benefit among patients. In contrast, bevacizumab, a humanized VEGF monoclonal antibody, exhibits evidence of apparent antitumor benefit, although these data remain controversial. In this review, we summarize how results of clinical trials evaluating bevacizumab to date influence the future of this therapeutic for recurrent and newly diagnosed glioblastoma patients.

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] To fully investigate the efficacy and safety of bevacizumab for glioblastoma.

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

Practical management of bevacizumab-related toxicities in glioblastoma. [2022] Bevacizumab, currently an option for treatment of different types of tumors including glioblastoma, has a peculiar toxicity profile related to its antiangiogenic effect. Because some bevacizumab-related adverse events can be life threatening, it is important to identify risk factors and to establish treatment protocols to minimize treatment-related morbidity and mortality. In glioblastoma patients, the risk of developing certain side effects, such as gastrointestinal perforation, venous thromboembolism, and intracranial hemorrhages, is slightly higher than in patients treated with bevacizumab for other tumor types. We performed a systematic review of the side effects of bevacizumab and their incidence, causal mechanisms, and available treatments. Finally, we identified risk factors and proposed preventive and therapeutic measures for these adverse events.

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] The proposed use of bevacizumab with radiotherapy/temozolomide for newly diagnosed glioblastoma raised potential safety concerns. Bevacizumab has been linked with stroke, bleeding events, and wound-healing complications in other tumor types; these events are of particular concern for glioblastoma (highly vascular tumors that are usually resected). Published data on the interaction of bevacizumab with radiotherapy/temozolomide are also limited. We report safety data from a phase III randomized trial (Avastin in Glioblastoma), focusing on these considerations.

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] We assessed the efficacy and safety of bevacizumab (BEV) through multiple lines in patients with recurrent glioblastoma who had progressed after first-line treatment with radiotherapy, temozolomide, and BEV.

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

Bevacizumab for glioblastoma. [2022] Individuals with glioblastoma are often characterized by older age, advanced neurologic manifestations at the primary stage, and unresectable tumors, and these factors are associated with poor treatment outcomes. Administration of bevacizumab (BV, Avastin(®)) promotes tumor regression and improves cerebral edema, and is expected to improve neurologic findings in many patients with malignant gliomas, including glioblastoma. Although the addition of BV to the conventional standard therapy (chemoradiotherapy with temozolomide) for newly diagnosed glioblastoma prolonged the progression-free survival time and the performance status of patients, it failed to extend overall survival time. However, more than 50% of glioblastoma patients show Karnofsky performance status ≤70 at initial presentation; therefore, BV should be used to improve or maintain their performance status as an initial treatment. Most of the adverse events of BV, except hypertension and proteinuria, occur as complications of glioblastoma, and explanation of the advantages and disadvantages of BV administration to patients is important. Herein, the efficacy, safety, and challenges of using BV for treating glioblastoma were reviewed.

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

Role of bevacizumab therapy in the management of glioblastoma. [2021] Glioblastoma is one of the most common primary brain tumors and one of the most difficult to treat. In population-based studies only 30% of patients will survive 1 year and in the most efficacious surgery, irradiation, and chemotherapy clinical trials approximately 20% will live 2 years. Bevacizumab is a recombinant, antivascular epidermal growth factor receptor (VEGF) monoclonal antibody with 6 VEGF-binding residues that binds to VEGF, preventing VEGF from binding to its target, VEGFR-1 and VEGFR-2, on endothelial cells. Through its binding to VEGF ligands bevacizumab reduces tumor angiogenesis and vasogenic brain edema; the consequences are that bevacizumab reduces the rate of glioblastoma tumor growth and its associated tumoral edema, thereby improving quality of life and survival for patients suffering from cerebral glioblastoma. In this review, we will summarize the studies that led to the use of bevacizumab in glioblastoma and the potential side-effects and complications that can be associated with its use and, finally, new opportunities for drug combinations with bevacizumab.