Efficacy and Safety of Anti-angiogenic Therapy With IV Bevacizumab in Patients With Symptomatic Cerebral Arteriovenous Malformations

Sponsor
Fondation Ophtalmologique Adolphe de Rothschild
Study ID
NCT06264531
Phase
PHASE2/PHASE3
Status
Recruiting
Apply to this trial

Conditions

  • Cerebral AV Malformation

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Bevacizumab — DRUG
    Bevacizumab 5 mg/kg as a slow infusion over 90 minutes every 14 days for a total of 6 injections
  • Placebo — DRUG
    NaCl 0.9% slow infusion over 90 minutes every 14 days for a total of 6 injections

Study Details

Brain arteriovenous malformations (AVMs) are responsible for hemorrhagic strokes, particularly in children and young adults. They can also be responsible for chronic neurological disorders: motor or sensory deficits, disturbances of higher functions, epilepsy or disabling headaches. The management of brain AVMs is complex and requires a multidisciplinary approach in an expert center. Available therapies include endovascular embolization, neurosurgical resection and/or radiosurgery. These procedures carry a risk of neurological complications, and are reserved for small AVMs located at a distance from highly functional cerebral structures. To date, no drug therapy is recommended if interventional treatment is not possible. Several studies on resected brain AVM tissue have demonstrated that these malformations are the site of significant evolutionary inflammatory and neo-angiogenesis processes. Other studies have specifically shown that VEGF (vascular endothelial growth factor) levels are increased in AVMs. More recently, a pre-clinical study showed that anti-angiogenic treatment with Bevacizumab reduced vascular proliferation within AVMs in mice. Finally, a Phase II clinical trial in patients with Rendu-Osler disease (a genetic vascular disorder characterized by recurrent epistaxis, cutaneous telangiectasia and the presence of visceral AVMs) showed a clinical benefit of IV Bevacizumab on the symptomatology of these vascular malformations, with a reduction in the risk of hemorrhage and the extent of hepatic arteriovenous shunts. A randomized Phase III trial is currently underway (NCT03227263) to assess the efficacy of IV Bevacizumab in Rendu-Osler disease. The aim of our study is to assess the efficacy of IV Bevacizumab on the disabling symptoms associated with symptomatic brain AVMs.

Key Dates

First listed
Feb 20, 2024
Start date
Jan 16, 2026
Status verified
Jan 2026
Primary completion
Jan 15, 2028
Completion
Jan 15, 2029

Study Design

Enrollment
54 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: bevacizumab
    Bevacizumab 5 mg/kg as a slow infusion over 90 minutes every 14 days for a total of 6 injections
  • Placebo Comparator: placebo
    NaCl 0.9% as a slow infusion over 90 minutes every 14 days for a total of 6 injections

Primary Outcome Measure

Proportion of patients showing at least one of the following improvements : cognition, neurological symptoms, epilepsy symptoms, headaches. [ Time Frame: month 6 ]

Central Contacts