Intravenous bevacizumab for symptomatic brain arteriovenous malformations
Evaluation of the Efficacy and Safety of Anti-angiogenic Therapy With Intravenous Bevacizumab in Patients With Symptomatic Cerebral Arteriovenous Malformations
This trial will try IV bevacizumab versus placebo to reduce symptoms in adults with symptomatic, high-grade cerebral arteriovenous malformations who are not candidates for surgery or radiosurgery.
Quick facts
| Phase | Phase2; Phase3 |
|---|---|
| Study type | Interventional |
| Enrollment | 54 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Fondation Ophtalmologique Adolphe de Rothschild Research network |
| Drugs / interventions | bevacizumab |
| Locations | 1 site (Paris, Île-de-France Region) |
| Trial ID | NCT06264531 on ClinicalTrials.gov |
What this trial studies
This phase 2/3 interventional trial gives eligible adults with symptomatic Spetzler-Martin grade III–V cerebral AVMs intravenous bevacizumab or a placebo to test safety and clinical benefit. The rationale is that many AVMs show inflammation and high VEGF-driven angiogenesis, and bevacizumab blocks VEGF signaling. Participants must have disabling symptoms and meet objective severity thresholds (for example MoCA, NIHSS, epilepsy or headache scores) and normal basic labs. Outcomes will include measures of neurological function, symptom scales, and safety monitoring over the treatment and follow-up period at the coordinating center in Paris.
Who should consider this trial
Good fit: Adults (≥18) with symptomatic cerebral AVMs graded III–V by Spetzler and Martin, with disabling symptoms (mRS>1), meeting the study's objective severity scores, ineligible for endovascular, surgical, or radiosurgical therapy, and with normal bone marrow, liver, and kidney function are ideal candidates.
Not a fit: Patients who are candidates for definitive interventional treatment, those with symptoms that are solely sequelae of prior bleeding, pregnant patients, those with abnormal labs, or with known allergy to bevacizumab are unlikely to benefit or are excluded.
Why it matters
Potential benefit: If successful, this approach could reduce neurological symptoms and slow or stabilize abnormal vessel growth by blocking VEGF-driven angiogenesis in inoperable AVMs.
How similar studies have performed: Pathology studies have shown VEGF upregulation in AVM tissue but clinical use of anti-VEGF therapy for cerebral AVMs is largely novel with limited prior clinical evidence.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Patient over 18 years of age * With a symptomatic cerebral AVM (chronic headache, focal neurological deficit, cognitive impairment, epilepsy) of Spetzler and Martin grade III, IV or V. * Whose symptoms are sufficiently severe to allow significant improvement with treatment: * MoCA score ≤ 25 and/or * NIHSS score ≥ 4 and/or * Epilepsy Balance Score ≥ 2 and/or * HIT-6 score ≥ 48 * With functional signs and symptoms not sequellar to a previous bleeding episode AND disabling (mRS\>1) * Ineligible for therapeutic intervention (endovascular or neurosurgery or radiosurgery) * With normal bone marrow, liver and kidney function * For women of childbearing potential: negative pregnancy test within 14 days of inclusion and effective contraception for up to 6 months after the end of treatment * Having received informed consent to participate in the study * Affiliated or beneficiary of a social security scheme Exclusion Criteria: * Known allergy to bevacizumab or an excipient. * Hypersensitivity to Chinese hamster ovary (CHO) cell products or other recombinant human or humanized antibodies. * Contraindication to cerebral MRI * Absolute or relative contraindication to gadolinium injection * Proteinuria ≥ 2+ on urine dipstick (patients with proteinuria ≥2+ on urine dipstick will need to have proteinuria ≤ 1g protein on 24-hour urine to be eligible) * Uncontrolled hypertension (PAS \>150 and/or PAD \> 100 mmHg) * History of hypertensive crisis or hypertensive encephalopathy * Congestive heart failure (New York Heart Association Grade II or higher) * Previous myocardial infarction or unstable angina in the preceding 12 months * Symptomatic peripheral vascular disease * Vascular disease (aortic aneurysm, aortic dissection) * Major surgery, open biopsy or major traumatic lesion within 4 weeks prior to inclusion, or anticipation of the need for major surgery during the study. * Biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to inclusion * History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess in the 6 months prior to inclusion * Significant unhealed wound, ulcer or bone fracture * Thrombotic episode within 6 months prior to inclusion * Atrial fibrillation * Patient under legal protection * Pregnant or breast-feeding women
Where this trial is running
Paris, Île-de-France Region
- Hfar — Paris, Île-de-France Region, France (Recruiting)
Study contacts
- Study coordinator: Jean-Philippe Désilles, MD, PhD
- Email: jpdesilles@for.paris
- Phone: 01 48 03 64 54
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.