Ignite Creation Date:
2025-12-24 @ 6:34 PM
Ignite Modification Date:
2025-12-30 @ 1:00 PM
Study NCT ID:
NCT07075757
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-07-20
First Post:
2025-07-10
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
In Situ Injection of Anti-angiogenics in Patients With Brain Arteriovenous Malformations Not Eligible for Exclusion Treatment
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Study Overview
Official Title:
In Situ Injection of Anti-angiogenics in Patients With Brain Arteriovenous Malformations Not Eligible for Exclusion Treatment: Phase I Trial
Status:
NOT_YET_RECRUITING
Status Verified Date:
2025-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
BLITZ
Brief 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.
Detailed Description:
The main objective of this trial is to evaluate the tolerance of 3 escalating doses of an in situ intra-arterial injection of bevacizumab in patients with a brain arteriovenous malformation (bAVM) considered non-suitable for an exclusion treatment to determine the Maximum Tolerated Dose (MTD) using the Dose-Limiting Toxicity rate (DLT) at 30 days after the injection. The dose limiting toxicity (DLT) is defined as the occurrence within 30 days of the in-situ injection of bevacizumab of one of the following events: Symptomatic venous/arterial thromboembolic events (symptomatic pulmonary embolism, symptomatic deep venous thrombosis, symptomatic ischemic stroke related to an arterial occlusion); Severe cytopenia defined as follows: Anemia defined as hemoglobin (Hb) level less than 8.0 g/dL (grade ≥ III, according to the CTCAE v5.0, 2017) Thrombocytopenia \< 50 G/L (grade ≥ III, according to the CTCAE v5.0, 2017), Neutropenia \< 1000/μL (grade ≥ IV according to the CTCAE v5.0, 2017); hypertension grade ≥ III (CTCAE v5.0, 2017); symptomatic intracranial hemorrhage resulting in transcient or permanent neurological deficit; any bleeding requiring transfusion; leukoencephalopathy grade ≥ III (CTCAE v5.0, 2017); Onset of intractable seizures ≥ Grade III (CTCAE v5.0, 2017); thrombo-embolic complication during the endovascular procedure leading to permanent deficit or to death; Intracranial arterial perforation with the microcatheter or the microguide wire during the endovascular procedure resulting in severe symptomatic hemorrhage (disability or death); any other serious adverse reaction (any untoward medical occurrence in a subject, to whom the medicinal product is administered, and which have a causal relationship with this treatment) resulting in any disability or death.
The secondary objectives and endpoints are to evaluate 1) the tolerance of 3 escalating doses of an in situ intra-arterial injection of bevacizumab in patients with a bAVM considered non-suitable for an exclusion treatment up to 12 months of follow-up; 2) To evaluate the efficacy of an in situ intra-arterial injection of bevacizumab in patients with a bAVM considered non-suitable for an exclusion treatment in terms of :Nidus volume size reduction at 6 and 12 months, Occurrence of cerebral bleeding events up to 12 months, Occurrence of seizures up to 12 months
The secondary objectives and endpoints are to evaluate 1) the tolerance of 3 escalating doses of an in situ intra-arterial injection of bevacizumab in patients with a bAVM considered non-suitable for an exclusion treatment up to 12 months of follow-up; 2) To evaluate the efficacy of an in situ intra-arterial injection of bevacizumab in patients with a bAVM considered non-suitable for an exclusion treatment in terms of :Nidus volume size reduction at 6 and 12 months, Occurrence of cerebral bleeding events up to 12 months, Occurrence of seizures up to 12 months
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 2023-506991-28-00 | CTIS | None | View |