Prospective Evaluation of the Efficacy of Sirolimus (Rapamune®) in the Treatment of Severe Arteriovenous Malformations

Arteriovenous Malformations Clinical Trial

— MAV-RAPA  

Official title:

Prospective Evaluation of the Efficacy of Sirolimus (Rapamune®) in the Treatment of Severe Arteriovenous Malformations

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02042326
• Other study ID #: PHRCN10-PR-DEVAUCHELLE
• Secondary ID: 2011-000321-69
• Status: Recruiting
• Phase: Phase 2
• Start date: September 12, 2014
• Est. completion date: September 2024

Study information

• Verified date: February 2023
• Source: Centre Hospitalier Universitaire, Amiens
• Contact: Bernard DEVAUCHELLE, MD, PhD
• Phone: +33322668325
• Email: devauchelle.bernard[@]chu-amiens.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of the study is to evaluate the efficacy and safety of sirolimus (oral form), to decrease the volume and symptoms due to superficial arteriovenous malformations (AVM). Sirolimus has properties that reduce the activity of the immune system (immunosuppressant), to fight against the proliferation of cancer cells (anti- tumor) and also reduce the proliferation of blood vessels (anti -vascular). Sirolimus is primarily used in transplant patients to prevent organ transplant rejection. Many animal and laboratory studies were carried out and demonstrate in particular the activity of sirolimus on vessels. It is this anti- vascular effect that could help treat arteriovenous malformations.

Description:

Anti-proliferative and anti-angiogenic properties of Sirolimus (Rapamycin®) are the basis of the rationale to use it in the treatment of arteriovenous malformations, for which the pathophysiology remains poorly understood. The interest of this class of drug is that inhibition of mTOR (mammalian target of rapamycin) may also block growth and / or angiogenic factors (other than VEGF) involved in the development of AVM. More specifically anti-VEGF drugs does not have that potential.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: September 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years and older

Eligibility

Inclusion Criteria:

• Patients (adults, adolescents and children older than 2 years), with arteriovenous malformation stage II + III or IV (according to Schöbinger's classification) : active or quiescent, marked or not by hemorrhagic phenomena.
• Patients (parents for minors) must sign a consent form established after clear information risks and expected benefits of the study.
• Patients (major and minor of childbearing age) must have effective contraception during the study period and continuing until 12 weeks after the end of treatment
• Negative pregnancy blood test for women of childbearing age.

Exclusion Criteria:

• Chronic or acquired immunosuppression :
• patients with transplanted organ or who received a hematopoietic stem cell
• patient with congenital immunodeficiency
• Patients implanted with chronic active infection associated with hepatitis B , hepatitis C or HIV
• Pregnant or nursing woman.
• Allergy to macrolides
• Allergy to peanut or soya
• Hypersensitivity to " Sirolimus " or any of the excipients of the investigational product
• Contraindications to performing an MRI
• Leukopenia below 1 000 /mm3
• Thrombocytopenia lower to 80,000 /mm3
• Anemia with Hb < 9 g/dl
• Elevated transaminase > 2.5 N
• History of cancer less than two years before the inclusion
• Surgery older than 2 months before inclusion
• Active infection (viral and bacterial ) on the date of inclusion
• Hypercholesterolemia > 7 mmol / l despite appropriate medical treatment
• Hyperlipidemia > 2 mmol / l despite appropriate medical treatment
• Uncontrolled diabetes
• Patients unable to follow a clinical study
• Major under guardianship, persons deprived of their liberty

Related Conditions & MeSH terms

• Arteriovenous Malformations
• Congenital Abnormalities
• Hemangioma

Intervention

Drug:
• Sirolimus
For patients with swallowing problems, and for children under 6 years and / or who have an inability to swallow tablets, the 1mg/ml solution form should be used.

Locations

Country	Name	City	State
Belgium	UCL	Bruxelles
France	CHU Amiens	Amiens
France	CHU Bordeaux	Bordeaux
France	CHU Dijon	Dijon
France	CHRU Lille	Lille
France	HCL Lyon	Lyon
France	APHM	Marseille
France	CHU Montpellier	Montpellier
France	CHU Nancy	Nancy
France	CHU Nice	Nice
France	APHP	Paris
France	CHU Strasbourg	Strasbourg
France	CHU Tours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire, Amiens

Countries where clinical trial is conducted

Belgium,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment efficacy at M12	The efficacy of treatment is a composite criteria based on: The proportion of patients with no evolution of the AVM during the study period,; The proportion of patients with a reduction in tumor volume of the AVM at least 30% of CT Angiography (CTA) criteria during the first year of the study (comparison of the volume of the AVM a year versus pre-inclusion).	After 12 months of treatment
Secondary	Treatment efficacy at M3		After 3 months of treatment
Secondary	Treatment efficacy at M6		After 6 months of treatment
Secondary	Treatment efficacy at M9		After 9 months of treatment
Secondary	Treatment tolerability	Number and description of serious advent events	One year
Secondary	Treatment Impact on Quality of life	Quality of life will be assessed before and at the end of the first year of treatment using a questionnaire given to patients. There is no questionnaire specifically tailored to vascular malformations in the literature. Thus the investigators adapted a document based on an evaluation of the quality of life for survivors of burn injury.	Before treatment initiation and after 12 months of treatment