Cetuximab + Bevacizumab for Brain Tumor
Recruiting in Palo Alto (17 mi)
Overseen byHeather McCrea, MD
Age: < 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: University of Miami
Disqualifiers: Pregnancy, Lactation, Significant medical conditions, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This study assesses the safety and efficacy of repeat monthly dosing of super-selective intra-arterial cerebral infusion (SIACI) of cetuximab and bevacizumab in patients \< 22 years of age.
Will I have to stop taking my current medications?
The trial requires that you stop chemotherapy at least three weeks before starting the treatment. If you are on steroids for brain-related issues, you can continue them as long as the dose is stable or decreasing for at least one week before joining the study. The protocol does not specify other medications, so it's best to discuss with the trial team.
What data supports the effectiveness of the drug combination Cetuximab and Bevacizumab for brain tumors?
Research shows that Cetuximab, when used alone, has been effective against certain brain tumors like glioblastoma multiforme (GBM), and Bevacizumab has shown promising results in improving survival rates in GBM patients. Additionally, a case study reported a complete remission of a relapsed brain tumor with the combination of Cetuximab and Bevacizumab, suggesting potential effectiveness.
12345Is the combination of Cetuximab and Bevacizumab safe for humans?
Bevacizumab can cause serious side effects like gastrointestinal perforation (a hole in the stomach or intestines), blood clots, and bleeding in the brain, especially in brain tumor patients. In a study with colorectal cancer patients, the combination of Cetuximab and Bevacizumab was generally well tolerated, with common side effects including rash, low magnesium levels, and fatigue.
678910How is the drug combination of Cetuximab and Bevacizumab unique for treating brain tumors?
The combination of Cetuximab and Bevacizumab for brain tumors is unique because Bevacizumab targets and neutralizes VEGF (a protein that promotes blood vessel growth), which is crucial for tumor survival and growth, while Cetuximab is an antibody that targets the epidermal growth factor receptor (EGFR), potentially offering a dual approach to inhibit tumor growth and improve patient outcomes.
311121314Eligibility Criteria
This trial is for patients under 22 with specific brain tumors that have come back or didn't respond to treatment. They need normal blood counts, liver and kidney function, and can't have had chemotherapy in the last three weeks. They must be able to perform daily activities at a certain level and not planning major surgery soon.Inclusion Criteria
Must have at least one confirmed and evaluable tumor site
Patients of reproductive age must agree to use a medically effective method of contraception during and for a period of three months after the treatment period. A pregnancy test will be performed on each premenopausal female of childbearing potential immediately prior to entry into the research study
I have a confirmed diagnosis of a specific type of brain tumor.
+9 more
Exclusion Criteria
Females 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. If they do not agree, they will be ineligible for the study
I do not have any major health or mental conditions that would make treatment risky for me.
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 monthly super-selective intra-arterial cerebral infusion of Cetuximab and Bevacizumab for up to one year
12 months
Monthly visits for infusion
Follow-up
Participants are monitored for safety and effectiveness after treatment
1 month
1 visit (in-person)
Participant Groups
The study tests monthly doses of cetuximab and bevacizumab delivered directly into the artery leading to the brain tumor in young patients. It aims to see how safe this method is and how well it works against aggressive brain tumors.
1Treatment groups
Experimental Treatment
Group I: SIACI of cetuximab and bevacizumabExperimental Treatment1 Intervention
Participants in this group will receive Cetuximab and Bevacizumab infusion into an artery each month for up to approximately one year.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Jackson Memorial HospitalMiami, FL
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Who Is Running the Clinical Trial?
University of MiamiLead Sponsor
References
Long term responses with cetuximab therapy in glioblastoma multiforme. [2021]Glioblastoma multiforme (GBM) is responsible for most of the deaths associated with primary brain tumors. Standard treatment includes maximal surgical resection followed by chemotherapy and concomitant radiotherapy. Most patients, however, recur shortly after treatment. Second line treatment has little efficacy and the majority of patients die soon from the disease. Recent advances in molecular biology have implicated the epidermal growth factor receptor (EGFR) signaling pathways in the progression and resistance to standard therapies for GBM. This has prompted the evaluation of EGFR tyrosine- kinase inhibitors with encouraging results. Cetuximab is a monoclonal antibody targeted against the extra cellular domain of the EGFR with activity against different tumor types, either alone or in combination with chemotherapy and/or radiation therapy. Here we describe three patients with recurrent, heavily pretreated, EGFR expressing GBM who responded to treatment with single agent cetuximab.
Anti-epidermal growth factor receptor monoclonal antibody cetuximab augments radiation effects in glioblastoma multiforme in vitro and in vivo. [2019]Previously, we demonstrated that the anti-epidermal growth factor receptor (EGFR) antibody cetuximab alone was effective against EGFR-amplified glioblastoma multiforme (GBM) cells in vivo and in vitro. The purpose of the present work was to study further the effectiveness of cetuximab as a monotherapy as well as combining it with radiation therapy or chemotherapy.
Bevacizumab in glioblastoma multiforme. [2015]Bevacizumab is a humanized IgG1 monoclonal antibody that selectively binds with high affinity to human VEGF and neutralizes VEGF' s biologic activity. Malignant gliomas are characterized by extensive microvascular proliferation and produce VEGF. Preclinical data indicate that angiogenesis is essential for the proliferation and survival of malignant glioma cells. Promising response rates, progression-free survival rates at 6 months and median overall survival in patients with recurrent glioblastoma multiforme (GBM) have been reported with bevacizumab, both in retrospective analyses and in prospective Phase II studies. In the pivotal randomized but noncomparative Phase II trial, a non-negligible percentage of patients survived beyond 1 and 2 years after the start of bevacizumab administration. However, randomized Phase III trial data on bevacizumab in recurrent GBM are lacking. Currently, bevacizumab is being studied in combination with temozolomide and radiation in previously untreated GBM patients in two large randomized Phase III trials.
Durable complete remission of a brainstem glioma treated with a combination of bevacizumab and cetuximab. [2021]Treatment of a relapsed glioma is a clinical challenge nowadays. New active treatments are required to treat these difficult diseases. Here we present a durable complete remission of a relapsed glioblastoma that has achieved a complete radiologic response with the combination of cetuximab and bevacizumab, in a third-line setting, that has offered a progression-free survival of 20 months. We consider here both potential mechanisms for the explanation of this result. First, the potential target of the cancer stem cells (CSCs) with these two antibodies, and second, the potential recruitment of the immune system to directly pursue the CSCs.
Stratified phase II trial of cetuximab in patients with recurrent high-grade glioma. [2022]To evaluate the antitumor activity and toxicity of single-agent cetuximab in patients with recurrent high-grade glioma (HGG) after failure of surgery, radiation therapy, and chemotherapy.
Bevacizumab use for recurrent high-grade glioma at McGill University Hospital. [2019]Bevacizumab, a humanized recombinant anti-vascular endothelial growth factor antibody, was approved in Canada in 2010 for the treatment of high-grade glioma. We report the effectiveness and safety of bevacizumab in the treatment of patients with recurrent high-grade gliomas at a single institution.
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.
Dual EGFR inhibition in combination with anti-VEGF treatment in colorectal cancer. [2022]Preclinical studies demonstrate that epidermal growth factor receptor (EGFR) signals through both kinase-dependent and independent pathways and that combining a small-molecule EGFR inhibitor, EGFR antibody, and/or anti-angiogenic agent is synergistic. We conducted a dose-escalation, phase I study combining erlotinib, cetuximab, and bevacizumab. The subset of patients with metastatic colorectal cancer was analyzed for safety and antitumor activity. Forty-one patients with heavily pretreated metastatic colorectal cancer received treatment on a range of dose levels. The most common treatment-related grade ≥2 adverse events were rash (68%), hypomagnesemia (37%), and fatigue (15%). Thirty of 34 patients (88%) treated at the full FDA-approved doses of all three drugs tolerated treatment without drug-related dose-limiting effects. Eleven patients (27%) achieved stable disease (SD) ≥6 months and three (7%) achieved a partial response (PR) (total SD>6 months/PR= 14 (34%)). Of the 14 patients with SD≥6 months/PR, eight (57%) had received prior sequential bevacizumab and cetuximab, two (5%) had received bevacizumab and cetuximab concurrently, and four (29%) had received prior bevacizumab but not cetuximab or erlotinib (though three had received prior panitumumab). The combination of bevacizumab, cetuximab, and erlotinib was well tolerated and demonstrated antitumor activity in heavily pretreated patients with metastatic colorectal cancer.
Retrospective study on bevacizumab in the treatment of non-small cell lung cancer with brain metastases. [2020]Bevacizumab was demonstrated to have efficacy in patients with non-small cell lung cancer (NSCLC) and brain metastases. However, cerebral toxicities were a major concern. This study aims to investigate the efficacy and risk factors of toxicity of bevacizumab in brain metastases.
Understanding and managing the possible adverse effects associated with bevacizumab. [2020]The adverse events associated with bevacizumab therapy are characterized, and the underlying pathophysiology, risk factors, frequency, and management of these events are described.
Bevacizumab and irinotecan in children with recurrent or refractory brain tumors: toxicity and efficacy trends. [2022]Bevacizumab, a monoclonal antibody targeting the vascular endothelial growth factor, has proven efficacy in some adult tumors; it is now proposed as a new therapeutic strategy for refractory or recurrent brain tumors in some children, either alone or combinated.
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.
Intracranial hemorrhage in patients with cancer treated with bevacizumab: the Memorial Sloan-Kettering experience. [2022]Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor approved for recurrent glioblastoma (GBM), metastatic breast, colorectal and non-small-cell lung cancers (NSCLC). There has been a potentially increased risk of intracranial hemorrhage (ICH) in patients receiving bevacizumab.
Safety and efficacy of bevacizumab with hypofractionated stereotactic irradiation for recurrent malignant gliomas. [2022]Preclinical studies suggest that inhibition of vascular endothelial growth factor (VEGF) improves glioma response to radiotherapy. Bevacizumab, a monoclonal antibody against VEGF, has shown promise in recurrent gliomas, but the safety and efficacy of concurrent bevacizumab with brain irradiation has not been extensively studied. The objectives of this study were to determine the safety and activity of this combination in malignant gliomas.