Bevacizumab Injection for Subdural Hematoma

(CHAI Trial)

Overseen By Hamza Shaikh, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: The Cooper Health System

Disqualifiers: Pregnancy, Intracranial pathology, Coagulation abnormalities, others

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: 8

140 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called bevacizumab (an injection) to determine its safety and effectiveness for people with chronic subdural hematomas, which are long-lasting blood buildups on the brain's surface. Researchers aim to find out if injecting this medication directly into certain brain arteries can reduce these blood buildups. The trial includes different groups, with some receiving treatment for blood on one side of the brain and others for both sides. Suitable participants have had a subdural hematoma for more than 10 days due to an injury. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that bevacizumab, when used to treat chronic subdural hematomas (cSDH), demonstrates positive safety results. In one study, patients who received bevacizumab injections into a specific artery in the brain did not experience major strokes or die within a month, suggesting the treatment was generally safe in the short term.

Bevacizumab is already FDA-approved for other conditions, which provides some reassurance about its safety. However, like any treatment, it can have side effects. In other uses, bevacizumab has been linked to negative effects, so monitoring patients closely is important.

The trial under consideration is in its early stages, meaning the treatment is still being tested for safety and effectiveness for this specific use. Participants play a key role in helping researchers learn more about the safety of bevacizumab for treating cSDH. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about bevacizumab injections for chronic subdural hematoma (cSDH) because it targets the condition in a new way. Unlike traditional treatments like surgery or corticosteroids, bevacizumab is a monoclonal antibody that blocks the vascular endothelial growth factor (VEGF), potentially reducing the abnormal blood vessel growth associated with cSDH. This could lead to less invasive treatment options and faster recovery times. The approach is being tested for both unilateral and bilateral cSDH, using different dosing strategies to optimize effectiveness.

What evidence suggests that bevacizumab infusion might be an effective treatment for chronic subdural hematomas?

Research has shown that bevacizumab, a drug that stops new blood vessels from growing, may help treat chronic subdural hematomas (cSDH). Studies have found that injecting bevacizumab into certain arteries can lead to positive outcomes for cSDH patients. For instance, some patients did not experience a recurrence or worsening of their hematomas, avoiding the need for additional surgery. This suggests that bevacizumab might help prevent the bleeding and fluid buildup common in this condition. The drug's ability to stop new blood vessel growth is considered important in reducing the size and pressure of these hematomas. Participants in this trial will receive different doses of bevacizumab, depending on whether they have unilateral or bilateral cSDH, to evaluate its effectiveness in these specific conditions. ^{1 2 3 4 6}

Who Is on the Research Team?

Jane Khalife, MD

Principal Investigator

The Cooper Health System

Manisha Koneru, MD

Principal Investigator

The Cooper Health System

Ajith J Thomas, MD

Principal Investigator

The Cooper Health System

Are You a Good Fit for This Trial?

This trial is for individuals with chronic subdural hematomas, a type of blood clot under the skull. Participants should be suitable candidates for arterial infusion procedures.

Inclusion Criteria

Can obtain informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization.

I have a chronic bleeding in my brain from an injury that happened over 10 days ago.

Exclusion Criteria

Patients with known hypersensitivity to bevacizumab

I need emergency surgery.

I have specific symptoms due to bleeding in my brain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Treatment Phase 1

Participants receive intra-arterial bevacizumab infusion to treat cSDH, with doses varying based on unilateral or bilateral condition

2 weeks

2 visits (in-person)

Treatment Phase 2

Continuation of bevacizumab infusion treatment with similar dosing as Phase 1

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of hematoma resolution and neurological symptoms

1 year

Multiple visits (in-person and virtual) at 3 months, 6 months, and 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab

Trial Overview The study tests two doses (2 mg/kg and 4 mg/kg) of Bevacizumab infused into arteries to treat chronic subdural hematomas. It aims to determine the safety and effectiveness of this treatment.

How Is the Trial Designed?

Group I: Phase 2 Unilateral cSDH/ 2mg/kg Arm Experimental Treatment 1 Intervention

During phase 2, single 2mg/kg dose of bevacizumab to treat unilateral cSDH

Group II: Phase 2 Bilateral cSDH/ 4mg/kg Arm Experimental Treatment 1 Intervention

During phase 2, two 2mg/kg doses (cumulatively 4mg/kg) of bevacizumab to treat bilateral cSDH

Group III: Phase 1 Unilateral cSDH/ 2mg/kg Arm Experimental Treatment 1 Intervention

During phase 1, single 2mg/kg dose of bevacizumab to treat unilateral cSDH

Group IV: Phase 1 Bilateral cSDH/ 4mg/kg Arm Experimental Treatment 1 Intervention

During phase 1, two 2mg/kg doses (cumulatively 4mg/kg) of bevacizumab to treat bilateral cSDH

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?

The Cooper Health System

Lead Sponsor

Trials

82

Recruited

35,600+

Society of Vascular and Interventional Neurology

Collaborator

Trials

2

Recruited

17,900+

Published Research Related to This Trial

Bevacizumab therapy, used for treating colon cancer, may be linked to the development and fluctuation of chronic subdural hematoma (CSDH) in patients, as seen in this 78-year-old man.

Neuroendoscope-assisted craniotomy proved to be an effective surgical method for the complete removal of organized CSDH, highlighting its utility in cases where simpler drainage methods are insufficient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroendoscope-assisted removal of an organized chronic subdural hematoma in a patient on bevacizumab therapy--case report. Takahashi, S., Yazaki, T., Nitori, N., et al.[2019]

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 study involving 18 rabbits, the VEGF inhibitor bevacizumab (BVZ) significantly prevented vasospasm in the basilar artery after inducing subarachnoid hemorrhage (SAH), as confirmed by magnetic resonance angiography (MRA).

BVZ also reduced apoptosis in the artery wall, suggesting that it may help protect against damage following SAH, highlighting its potential therapeutic role in managing vascular complications after such events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What is the restorative effect of VEGF inhibitor bevacuzimab against subarachnoid hemorrhage in an experimental model? Demirci, AY., Güvenç, Y., Özeren, E., et al.[2023]

A 55-year-old woman with metastatic colorectal cancer developed a subarachnoid hemorrhage after treatment with bevacizumab, a drug that inhibits vascular endothelial growth factor, suggesting a possible link between the medication and the hemorrhage.

The patient's neurological symptoms and increased blood flow velocities in the brain resolved with medical treatment within 10 days, indicating that while bevacizumab may have contributed to the hemorrhage, effective management can lead to recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pretruncal subarachnoid hemorrhage and high cerebral blood flow velocities with bevacizumab therapy. Baizabal-Carvallo, JF., Alonso-Juárez, M., Salas, I.[2016]

Bevacizumab (Avastin) received accelerated FDA approval for treating glioblastoma multiforme (GBM) based on its ability to produce partial responses in 25.9% of patients in one trial and 19.6% in another, with median response durations of approximately 4.2 and 3.9 months, respectively.

While bevacizumab shows efficacy in GBM treatment, it is associated with significant adverse events, including serious risks like CNS hemorrhage and thromboembolic events, highlighting the need for careful patient monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA drug approval summary: bevacizumab (Avastin) as treatment of recurrent glioblastoma multiforme. Cohen, MH., Shen, YL., Keegan, P., et al.[2022]

In a study of 21 patients treated with bevacizumab and anticoagulation for a median of 72 days, there were no major lobar hemorrhages, indicating that anticoagulation may be safe in this context.

While some patients experienced small, asymptomatic hemorrhages, the study suggests that anticoagulation does not increase the risk of significant bleeding when using bevacizumab, contrasting with cases of symptomatic hemorrhages in patients not on anticoagulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of anticoagulation use and bevacizumab in patients with glioma. Nghiemphu, PL., Green, RM., Pope, WB., et al.[2022]

A patient with glioblastoma multiforme experienced a traumatic subarachnoid hemorrhage (SAH) while being treated with bevacizumab, but showed no signs of vasoconstriction, a potential complication associated with the drug.

Bevacizumab was safely resumed five weeks after the SAH without any recurrence of bleeding or vasoconstriction, marking the first documented case of continuing this treatment post-SAH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab for glioblastoma multiforme after traumatic subarachnoid hemorrhage. Lukas, RV., Goldenberg, F., Nicholas, MK.[2018]

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 study of 115 patients with chronic subdural hematoma (CSDH), higher concentrations of vascular endothelial growth factor (VEGF) in hematoma fluid were significantly associated with specific MRI types, indicating a potential biomarker for assessing CSDH severity.

Patients with type 1 CSDH, which had the highest VEGF levels, showed a higher recurrence rate compared to those with type 4, suggesting that VEGF concentration could help predict the likelihood of CSDH recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correlation of vascular endothelial growth factor with magnetic resonance imaging in chronic subdural hematomas. Li, F., Hua, C., Feng, Y., et al.[2018]

Bevacizumab, a monoclonal antibody targeting VEGF, has shown efficacy in treating malignant tumors and was successfully used in a case of chronic subdural hematoma (CSDH) associated with recurrent glioblastoma, suggesting a potential therapeutic role for CSDH.

The presence of high levels of VEGF in the outer membrane of CSDH indicates that VEGF may play a significant role in the development and recurrence of CSDH, warranting further investigation into its mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case of complete clearance of chronic subdural hematoma accompanied by recurrent glioblastoma multiforme after administration of bevacizumab. Suzuki, K., Kawataki, T., Kanemaru, K., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11580117/

Bevacizumab: The future of chronic subdural hematoma - PMC Bevacizumab's ability to inhibit excessive neovascularization suggests it may have a potential role in treating chronic subdural hematomas (cSDH).

2. ahajournals.org ahajournals.org/doi/10.1161/SVIN.124.001409

Intra‐arterial Selective Bevacizumab Administration in the ... Our experience demonstrates initial, positive results with intra‐arterial injection of bevacizumab into the middle meningeal artery. There has ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06510582

Chronic Subdural Hematoma Treatment With Intra-Arterial ... The goal of this clinical trial is to test whether infusing bevacizumab into the middle meningeal arteries can be used to treat chronic subdural hematomas (cSDH) ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S187887502400994X

Investigation of the Efficacy of Bevacizumab Treatment in ... Wang et al. reported that in a subdural hematoma model, a 3 mg/kg dose of Ato was significantly more effective compared to an 8 mg/kg dose in rats.20 Weis et al ...

5. jnis.bmj.com jnis.bmj.com/content/16/Suppl_1/A42.1

O-055 Selective middle meningeal artery bevacizumab ... Conclusions For all hemispheres treated, there were no hematoma recurrence or progression requiring surgical drainage or MMAE within 3 months except one who ...

6. journals.sagepub.com journals.sagepub.com/doi/abs/10.1177/15910199241298727

Bevacizumab: The future of chronic subdural hematoma This literature review explores the connection between bevacizumab and cSDH, focusing on the pharmacological, safety, and delivery aspects of ...