Overseen ByJohn Boockvar, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Northwell Health
Must not be taking: Bevacizumab
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 tumors, glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA), 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, and 3-4 years for AA. Initial therapy consists of either surgical resection, external beam radiation or both. All patients experience a recurrence after first-line therapy, so improvements in both first-line and salvage therapy are critical to enhancing quality-of-life and prolonging survival. It is unknown if currently used intravenous (IV) therapies even cross the blood brain barrier (BBB). The investigators have shown in a previous phase I trial that a single Super-selective Intraarterial Cerebral Infusion (SIACI) of Bevacizumab (up to 15mg/kg) is safe and effective in the treatment of recurrent GBM. Therefore, this phase I/II clinical research trial is an extension of that trial in that the investigators seek to test the hypothesis that repeated dosing of intraarterial Bevacizumab is safe and effective in the treatment of recurrent malignant glioma. By achieving the aims of this study the investigators will also determine if IV therapy with Bevacizumab should be combined with repeated selected intraarterial Bevacizumab to improve progression free and overall survival. The investigators expect that this project will provide important information regarding the utility of repeated SIACI Bevacizumab therapy for malignant glioma, and may alter the way these drugs are delivered to the patients in the near future.
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.
What data supports the idea that Bevacizumab for Brain Cancer (also known as: Bevacizumab, Avastin) is an effective drug?
The available research shows that Bevacizumab may improve the quality of life for patients with glioblastoma, a type of brain cancer, but it does not necessarily extend overall survival. Some studies suggest that it helps in delaying the progression of the disease when combined with other treatments like radiotherapy and temozolomide, especially in certain patient subgroups. However, there are concerns that it might reduce the effectiveness of standard treatments and increase the risk of the cancer spreading by using normal blood vessels. Overall, while Bevacizumab can be beneficial in some ways, its effectiveness compared to other treatments is mixed.
12345What safety data is available for Bevacizumab in brain cancer treatment?
Bevacizumab, also known as Avastin, has a unique toxicity profile due to its antiangiogenic effects. In glioblastoma patients, there is a slightly higher risk of adverse events such as gastrointestinal perforation, venous thromboembolism, and intracranial hemorrhages compared to other tumor types. Safety concerns include stroke, bleeding events, and wound-healing complications, especially when combined with radiotherapy/temozolomide. A meta-analysis showed an increased risk of cerebrovascular events, including CNS ischemic events and CNS hemorrhage, with a relative risk of 3.28 compared to controls. The risk varies with dose and tumor type, with higher risks observed in metastatic colorectal cancer. Preventive and therapeutic measures are recommended to manage these risks.
16789Is the drug Bevacizumab a promising treatment for brain cancer?
Bevacizumab, also known as Avastin, is a drug that has shown promise in treating brain cancer, specifically glioblastoma. It has been approved in the USA for recurrent cases because it can improve the quality of life and has a higher response rate compared to other treatments. It works by targeting blood vessels that help tumors grow, which can slow down the progression of the disease.
12101112Eligibility Criteria
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 am 18 years old or older.
+2 more
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.
Trial Timeline
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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Group I: Arm 2Experimental Treatment1 Intervention
Group II: Arm 1Experimental Treatment1 Intervention
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Lenox Hill Brain Tumor CenterNew York, NY
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Who Is Running the Clinical Trial?
Northwell HealthLead Sponsor
Feinstein Institute for Medical ResearchCollaborator
References
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.
The paradoxical effect of bevacizumab in the therapy of malignant gliomas. [2021]One rationale behind the use of agents that inhibit vascular endothelial growth factor in the therapy of primary CNS malignancies is based upon the concept that normalization of tumor vasculature with a decrease in tumor interstitial pressure will improve access of cytoreductive drugs and improve radiotherapy efficacy due to increased oxygen delivery. However, several studies have raised the concern that these agents may both rapidly restore the low permeability characteristics of the blood-brain barrier and counteract the beneficial effect of pseudoprogression. The result may be decreased therapeutic efficacy while increasing infiltration by co-opting normal vessels. In this discussion, we examine both histologic and radiographic tumor progression in the context of antiangiogenic agents. Issues dealing with the safety of bevacizumab (Avastin®, Genentech, South San Francisco, CA) and its potential to decrease efficacy of standard radiochemotherapy when used to treat patients with newly diagnosed malignant glioma are emphasized.
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.
Bevacizumab-containing regimen in relapsed/progressed brain tumors: a single-institution experience. [2020]The aim of the study is to assess tumor response, treatment-related toxicities, progression-free survival (PFS), and overall survival (OS) in patients with relapsed/refractory brain tumors treated with bevacizumab-containing regimen.
Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. [2022]To evaluate single-agent activity of bevacizumab in patients with recurrent glioblastoma.
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.
Increased risk of cerebrovascular events in patients with cancer treated with bevacizumab: a meta-analysis. [2021]Arterial ischemia and hemorrhage are associated with bevacizumab, an inhibitor of vascular endothelial growth factor that is widely used to treat many types of cancers. As specific types of arterial ischemia and hemorrhage, cerebrovascular events such as central nervous system (CNS) ischemic events and CNS hemorrhage are serious adverse events. However, increased cerebrovascular events have not been uniformly reported by previous studies. New randomized controlled trials (RCTs) have been reported in recent years and we therefore conducted an up-to-date meta-analysis of RCTs to fully characterize the risk of cerebrovascular events with bevacizumab. We searched the databases of PubMed, Web of Science, and the American Society of Clinical Oncology conferences to identify relevant clinical trials up to February 2014. Eligible studies included prospective RCTs that directly compared patients with cancer treated with and without bevacizumab. A total of 12,917 patients from 17 RCTs were included in our analysis. Patients treated with bevacizumab had a significantly increased risk of cerebrovascular events compared with patients treated with control medication, with a relative risk of 3.28 (95% CI, 1.97-5.48). The risks of CNS ischemic events and CNS hemorrhage were increased compared with control, with RRs of 3.22 (95% CI, 1.71-6.07) and 3.09 (95% CI, 1.36-6.99), respectively. Risk varied with the bevacizumab dose, with RRs of 3.97 (95% CI, 2.15-7.36) and 1.96 (95% CI, 0.76-5.06) at 5 and 2.5 mg/kg/week, respectively. Higher risks were observed in patients with metastatic colorectal cancer (RR, 6.42; 95% CI, 1.76-35.57), and no significant risk was observed in other types of tumors. In conclusion, the addition of bevacizumab significantly increased the risk of cerebrovascular events compared with controls, including CNS ischemic events and CNS hemorrhage. The risk may vary with bevacizumab dose and tumor type.
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.
Safety of bevacizumab in patients with non-small-cell lung cancer and brain metastases. [2022]Patients with non-small-cell lung cancer (NSCLC) and brain metastases have previously been excluded from trials of bevacizumab because of suspected risk of CNS hemorrhage. This phase II trial, AVF3752g (PASSPORT), specifically addressed bevacizumab safety (incidence of grade > or = 2 CNS hemorrhage) in patients with NSCLC and previously treated brain metastases.
Bevacizumab for the treatment of glioblastoma. [2022]Glioblastoma (GB) is the most common adult malignant primary brain tumor that arises from glial precursor cells. Survival in GB is variable ranging from 6 to 20 months notwithstanding current standard of care (SOC) treatment. Therapy has improved, but nonetheless GB is still invariably recurrent and incurable. Treatment options at recurrence include re-operation with or without carmustine (BCNU) wafer implantation (Gliadel), re-irradiation and standard/experimental chemo- or targeted therapy. Recurrent GB radiographic response rates to cytotoxic chemotherapy are less than 10% and median 6-month progression-free survival (PFS6) is 15%. With the recognition of the importance of tumor angiogenesis and the development of targeted therapy based on angiogenic inhibition, two pivotal trials of the VEGF-directed monoclonal antibody, bevacizumab (BEV, Avastin), were conducted in recurrent GB. Based upon the results of these two prospective US trials (median radiographic response rate: 25%; PFS6: 40%), BEV as a single agent was granted accelerated approval in the USA for recurrent GB. This review is a summary of current literature and clinical trials research in the role of BEV for the treatment of newly diagnosed and recurrent GB and potential future use of anti-angiogenic therapies in the management of GB.
Vascular phenotypes in primary non-small cell lung carcinomas and matched brain metastases. [2021]Anti-angiogenic therapy with bevacizumab (an anti-vascular endothelial growth factor (VEGF) antibody) predominantly targets immature blood vessels. Bevacizumab has shown a survival benefit in non-small cell lung carcinoma (NSCLC) and has recently been demonstrated to be safe in patients with brain metastases. However, it is not known whether bevacizumab is effective against brain metastases or whether metastases are representative of their primary in terms of VEGF expression, hypoxia, proliferation and vascular phenotype. The aim of this study was to evaluate these factors in a series of matched primary NSCLCs and brain metastases.
FDA drug approval summary: bevacizumab (Avastin) as treatment of recurrent glioblastoma multiforme. [2022]On May 5, 2009, the U.S. Food and Drug Administration granted accelerated approval to bevacizumab injection (Avastin; Genentech, Inc., South San Francisco, CA) as a single agent for patients with glioblastoma multiforme (GBM) with progressive disease following prior therapy. The approval was based on durable objective responses (independent radiologic review with stable or decreasing corticosteroid use). Two trials evaluating bevacizumab, 10 mg/kg by i.v. infusion every 2 weeks, were submitted. One trial also randomized patients to bevacizumab plus irinotecan treatment. All patients had received prior surgery, radiotherapy, and temozolomide. Patients with active brain hemorrhage were excluded. One trial enrolled 78 independently confirmed GBM patients. Partial responses were observed in 25.9% (95% confidence interval [CI], 17.0%-36.1%) of the patients. The median response duration was 4.2 months (95% CI, 3.0-5.7 months). The second trial enrolled 56 GBM patients. Partial responses were observed in 19.6% (95% CI, 10.9%-31.3%) of the patients. The median response duration was 3.9 months (95% CI, 2.4-17.4 months). Safety data were provided for the first study. The most frequently reported bevacizumab adverse events of any grade were infection, fatigue, headache, hypertension, epistaxis, and diarrhea. Grade 3-5 bevacizumab-related adverse events included bleeding/hemorrhage, central nervous system (CNS) hemorrhage, hypertension, venous and arterial thromboembolic events, wound-healing complications, proteinuria, gastrointestinal perforation, and reversible posterior leukoencephalopathy. The attribution of certain adverse events (e.g., CNS hemorrhage, wound-healing complications, and thromboembolic events) to either bevacizumab, underlying disease, or both could not be determined because of the single-arm, noncomparative study design.