Clinical trial NCT02042326: Prospective Evaluation of the Efficacy of Sirolimus (Rapamune®) in the Treatment of Severe Arteriovenous Malformations
Official title: Prospective Evaluation of the Efficacy of Sirolimus (Rapamune®) in the Treatment of Severe Arteriovenous Malformations
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Arteriovenous Malformations
Keywords: Arteriovenous Malformations
Sirolimus
Maxillofacial Surgery
Lead sponsor: Centre Hospitalier Universitaire, Amiens
Sponsor class: OTHER
First posted: 2014-01-22
Enrollment: 50
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Treatment efficacy at M12
timeFrame: After 12 months of treatment
Secondary outcomes:
measure: Treatment efficacy at M3
timeFrame: After 3 months of treatment
measure: Treatment efficacy at M6
timeFrame: After 6 months of treatment
measure: Treatment efficacy at M9
timeFrame: After 9 months of treatment
measure: Treatment tolerability
timeFrame: One year
measure: Treatment Impact on Quality of life
timeFrame: Before treatment initiation and after 12 months of treatment
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: UCL
city: Amiens
country: France
facility: CHU Amiens
city: Bordeaux
country: France
facility: CHU Bordeaux
city: Dijon
country: France
facility: CHU Dijon
city: Lille
country: France
facility: CHRU Lille
city: Lyon
country: France
facility: HCL Lyon
city: Marseille
country: France
facility: APHM
city: Montpellier
country: France
facility: CHU Montpellier
city: Nancy
country: France
facility: CHU Nancy
city: Nice
country: France
facility: CHU Nice
city: Paris
country: France
facility: APHP
city: Strasbourg
country: France
facility: CHU Strasbourg
city: Tours
country: France
facility: CHU Tours
Study officials:
affiliation: CHU Amiens
name: Bernard DEVAUCHELLE, MD, PhD
role: STUDY_DIRECTOR
affiliation: HCL Lyon
name: Emmanuel MORELON, MD, PhD
role: STUDY_CHAIR
References: