Efficacy and Safety of the Mammalian Target of Rapamycin (mTor Rapamycin) Inhibitor in Vascular Malformations

Clinical Study on Efficacy and Safety of the mTor Rapamycin Inhibitor Found in the Complex Vascular Malformations

The phosphatidylinositol 3-kinase (PI3Kinase)/Protein Kinase B (AKT)/mammalian target of rapamycin (mTor) pathway plays a role on the development and the 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 lymphatic-vascular organisations suggesting an appealing therapeutic target to treat patients with complex vascular malformations.

The aim of this clinical study is to prospectively evaluate the efficacy and the safety of the Rapamycin, an mTOR inhibitor, to treat children and adults with microcystic lymphatic malformations, general lymphatics abnormalities (GLA) or complex vascular malformations for which conventional therapies as surgery or sclerotherapy are ineffective or associated with high risk of important complications.

Inclusion Criteria:

• Patients with complex vascular abnormalities to be threat by a systemic therapy
• Patients must have adequate liver function (LDL-cholesterol, triglycerides,…)
• Patients must have adequate organ function: neutrophils >1500/mm³, Hb > 8,0 g et platelets> 50.000/mm³ (no platelets limits for the Kasabach Merritt syndrome)
• Patients must have adequate renal function(normal creatinin depending on the age), clearance > 70 ml/min/1.73m² and Urin Protein Creatinine ratio <0.3 g.
• Karnofsky or Landry > 50

Exclusion Criteria:

• Dental equipments or prosthesis interfering onto a radiological examen
• Other uncontrolled medical condition (uncontrolled diabetes, hypertension…)
• Concomitant drugs such as inhibitors/inducers of cytochrome P450 3A4 (CYP3A4)
• Immunocompromised patients, including known seropositivity for HIV
• Digestive problems modifying the absorption of Rapamycin (gastric tube feeding accepted)
• Pregnant or nursing (lactating) women
• Prior treatment with phosphatidylinositol 3-kinase (PI3K) and/or mTOR inhibitors