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NOT YET RECRUITING

NCT07075757

PHASE1

In Situ Injection of Anti-angiogenics in Patients With Brain Arteriovenous Malformations Not Eligible for Exclusion Treatment

Sponsor: Assistance Publique - Hôpitaux de Paris

View on ClinicalTrials.gov

Summary

Brain arteriovenous malformations (bAVMs) are rare aggressive vascular malformations affecting mostly young and healthy adults. The most frequent revealing condition (in almost 50% of cases) is an intra-cerebral hemorrhage, which is a considerable source of disability and mortality. The only way to prevent a bleeding or a rebleeding is to perform an exclusion treatment (endovascular embolization, microsurgery, stereotactic radiosurgery, or a combination of these techniques). The major drawback of these treatments is the risk of severe complications, which can reach 20%, especially in patients presenting a bAVM with complex angio-architecture (i.e., grade IV to V in the Spetzler Martin grading scale). There is a growing evidence about the strong implication of angiogenesis (mainly mediated by the type A vascular endothelial growth factor \[VEGF-A\]) on the size and growth of the bAVM and even in the occurrence of bleeding events. Our hypothesis is that an in situ injection of bevacizumab, a monoclonal antibody inhibiting VEGF-A, in patients with bAVM deemed not suitable for exclusion treatment may be safe and help to reduce the nidus volume.

Official title: In Situ Injection of Anti-angiogenics in Patients With Brain Arteriovenous Malformations Not Eligible for Exclusion Treatment: Phase I Trial

Key Details

Gender

All

Age Range

18 Years - 65 Years

Study Type

INTERVENTIONAL

Enrollment

Start Date

2025-10-01

Completion Date

2028-11-01

Last Updated

2025-07-20

Healthy Volunteers

Conditions

Brain Arteriovenous Malformations

Interventions

DRUG

Single in situ intra-arterial injection of bevacizumab

3 Escalating doses of an in situ intra-arterial injection of Bevacizumab (5 mg/kg, 7.5 mg/kg, 10 mg/kg)

Inclusion Criteria: 1. Age ≥18 and \< 65 years at the time of inclusion 2. bAVM (i.e.: located in the brain, brain stem or cerebellum) 3. Spetzler-Martin grade IV - V on a brain MRI performed less than 2 months before inclusion 4. History of rupture and/or with intractable symptoms related to the bAVM (i.e.: intractable seizure, steal phenomenon, compressive symptoms) 5. bAVM deemed unsuitable for exclusion invasive treatment 6. Adequate bone marrow function at inclusion : * Hemoglobin (Hb) levels more than 13.5 g/dL in males and Hb levels more than 12.5 g/dL in females. * Platelet count ≥ 150 G/L * Leukocytes count ≥ 3000/μL * Neutrophils count ≥ 1500/μL 7. Normal liver function (alanine transaminase \[ALT\] \< 56 UI/L and aspartate aminotransferase \[AST\] \< 40 UI/L) at inclusion 8. Normal renal function (creatinine clearance ≥ 30 ml/min calculated with the Cockcroft-Gault formula) at inclusion 9. Complete COVID-19 vaccinal scheme, according to the French recommendations 10. Affiliation to French Healthcare system (AME excluded) 11. Signed informed consent Exclusion Criteria: 1. Diffuse bAVM (like proliferative angiopathy) that cannot be assessed in terms of volume by cross-sectional imaging on MRI 2. Inability/contraindication to undergo MRI (Pacemaker, iron metallic items, cochlear implants, claustrophobia) 3. Coagulation disorders (prothrombin time \< 50% or Platelet count \< 150 G/L) 4. Any congenital predisposition to coagulation disorder 5. Any disease requiring full anticoagulation 6. History of cancer, except baso-cellular carcinoma 7. Congestive cardiac failure 8. Pre-existing coronary disease 9. Unstable medical or psychiatric illness 10. Any history of clinically significant thrombotic episode within the last 6 months 11. Any history of atrial fibrillation 12. Proteinuria (albumin excretion rate \> 30 mg/day) 13. Blood hypertension grade ≥ II (CTACE v5.0, 2017) 14. Past history of a gastro-intestinal fistula 15. Past history of a vaginal fistula 16. Past history of open surgery within the last 28 days 17. Infectious syndrome within the last month 18. Any other contra-indication to bevacizumab administration 19. Any contra-indication to general anesthesia 20. Pregnancy or lactating woman 21. Woman without efficacy contraception (combined hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner, sexual abstinence) all along study participation, and until 6 months after the bevacizumab administration, for woman of childbearing potential 22. Seropositivity for HIV, HCV or HBV 23. Severe and proven allergy to iodinated contrast material or Gadolinium 24. Participation in another interventional clinical trial evaluating a health product or any randomized clinical trial 25. Patients under legal protection (tutorship or curatorship) and patient deprived of freedom

Locations (5)

CHU de Limoges, Hôpital Dupuytren

Limoges, France

CHU de Nancy, Hôpital Central

Nancy, France

APHP, Hôpital Pitié-Salpêtrière

Paris, France

Centre Hospitalier Sainte-Anne