suPERficial slow-flow vascular malFORMations treated with sirolimUS

Phase 1

• Conditions: vascular malformations; MedDRA version: 18.0 Level: PT Classification code 10074979 Term: Vascular malformation System Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

• Registration Number: EUCTR2015-001096-43-FR
• Lead Sponsor: CHRU de Tours

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-07-23
• Last Update Posted: 10 December 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 50

Inclusion Criteria

* Patients aged from 6 years to 18 years (when submitting the intention letter, we aimed to include children from 12 months to 18 years. The minimal age was changed in the current protocol to children up to 6 years, because our protocol requires repeated MRI, which is non invasive imaging but requires sedation under the age of 5-6 years. We thus found too invasive to perform repeated sedations in toddlers)
* With a slow-flow VM confirmed by MRI, included or not into a genetic disorder, among the following:
- microcystic lymphatic malformation
- mixed micro- and macrocystic malformation
- venous malformation
- combined lymphatic and venous malformation
* Malformation voluminous (defined as = 5 % of body surface) and complicated (pain, functional impairment, bleeding, seepage)
* Extended to the underlying subcutaneous tissue, to the fascias, the muscles and/or the underlying bone
* MRI of the VM performed within 8 months
* Vaccination schedule updated
* Informed, written consent of the subject’s parents or the 18 years old subject (see §9.3 Screening and baseline visits)
* Cooperative parent or subject, aware of the necessity and duration of controls so that perfect adhesion to the protocol could be expected
* Subjects or subject’s parents covered by or having the rights to social security
Are the trial subjects under 18? yes
Number of subjects for this age range: 45
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 5
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Non Inclusion criteria linked to the condition
?Slow-flow VMs which are only macrocystic lymphatic malformations
?Visceral life-threatening involvement
Non inclusion criteria linked to sirolimus
?Patients who received prior per os treatment with an mTOR inhibitor
?Immunosuppression (immunosuppressive disease or immunosuppressive treatment)
?Known chronic infectious disease
?History of cancer in the 2 previous years
?Brest feeding or pregnant women, or women on childbearing age without effective contraception, up to 12 weeks after treatment discontinuation
?Known allergy to mTOR inhibitor
?Concomitant treatment that inhibits or activates CYP3A4, and P-gp glycoprotein, cytotoxic drugs, antilymphocyte immunoglobulines and metoclopramide
?Intolerance to fructose, intolerance or malabsorption to glucose, galactose, metabolic insufficiency in sucrase-isomaltase, metabolic defect in lactase
?Known allergy to peanuts or soyabean
?Liver insufficiency (elevated transaminases > 2.5 N)
?Anemia with Hb < 9 g/dl
?Leukopenia < 1000/mm3
?Thrombocytopenia < 80 000/mm3
?Hypercholesterolemia (LDL-cholesterol = 2g/l)
?Patients with risk of opportunistic infections
?Live attenuated vaccine up to 3 months after sirolimus discontinuation
Other non inclusion criteria
?Contraindication of MRI
?Known allergy to lidocaïne (only for patients who accept genetic analysis1)
?Subject already participating to a therapeutic study

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified