The phosphatidylinositol 3-kinase (PI3Kinase)/Protein Kinase B (AKT)/mammalian target of rapamycin (mTor) pathway plays a role on the development and the venous/lymphatic vascular organisations. The investigators want to study the efficacy and the safety of Rapamycin, an mTor inhibitor.
The complex vascular malformations induce chronical pains and organic dysfunctions causing significant morbidity and mortality. Therefore, the investigators need to establish guidelines in order to treat these pathologies. Standard treatments such as surgery or interventional radiology are of limited efficacy and related to a high level of recurrences as well as complications. Recent preclinical studies have shown the important role of the PI3Kinase/AKT/mTor pathway on the development and the venous/lymphatic vascular organisations suggesting an appealing therapeutic target to treat patients with venous, lympathic or complex vascular malformations. Investigators will realize a multicentric phase III study enrolling a higher number of patients to statistically evaluate the efficacy and the safety of the Rapamycin, an mTOR inhibitor, in the treatment of children and adults with vascular malformations for which conventional therapies such as surgery or sclerotherapy are ineffective or associated with high risk of important complications. Nearly 250 patients (200 adults and 50 children) will be enrolled in several european centers.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
250
evaluate the efficacy and safety of sirolimus in these patients
Cliniques Universitaires Saint-Luc, Université Catholique de Louvain Bruxelles
Brussels, Brussels Capital, Belgium
RECRUITINGCHU Caen
Caen, Brittany Region, France
RECRUITINGUniversitätsklinikum Freiburg
Freiburg im Breisgau, Germany
NOT_YET_RECRUITINGSelf-assesment (or parent assesment), using visual anagogic scale (0-10) of efficacy of sirolimus
* Global treatment efficacy * Pain * Local complications/symptoms (bleeding, skin tension, esthetic and functional impairment)
Time frame: every 3 months, up to 2-year period.
Number of enrolled patients with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: every month during the first three months and then every three months for a 2-year-treatment period
Self assessment of quality of life change induced by sirolimus
Measured by quality of life questionnaire (adapted to MOS SF-36 survey).
Time frame: every 3 months, up to 2-year period.
Volumetric changes of the malformation on sirolimus, based on magnetic resonance imaging (MRI) 12 months after sirolimus onset.
Relative change of volume of the vascular malformation between the baseline MRI (before sirolimus onset) and the 12-month MRI (during sirolimus treatment)
Time frame: At 12 month
Efficacy of sirolimus
Change in plasma levels fibrinogen and/ or D-dimers, reflecting improvement in an abnormal intravascular coagulation consumption
Time frame: every three months, up to 2-year period
Efficacy of sirolimus measured on digital photographs
Qualitative assessment of efficacy on digital photographs
Time frame: every three months, up to 2-year period
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