TOPical sirolimus in linGUal microkystic lymphatic malformation

Phase 2

Completed

Conditions: Lingual microcystic lymphatic malformations (LMLMs) are rare congenital vascular malformations, presenting as clusters of cysts filled with lymph fluid or blood. They are responsible for a heavy burden even with small well-limited lesions because of oozing, bleeding, infections, or even speech, chewing or breathing impairment. Pain and aesthetic prejudice are also frequently reported

Registration Number: 2024-515955-39-01

Lead Sponsor: Centre Hospitalier Regional Universitaire De Tours

Brief Summary: To evaluate the efficacy and safety of a 1mg/mL sirolimus solution applied once daily on the anterior part of lingual microcystic lymphatic malformation of any stage in children and adults after 4, 8, 12, 16, 20 and 24 weeks of treatment as compared to usual care (no treatment).

Detailed Description: Not available

Recruitment & Eligibility

Status: Ended

Sex: Not specified

Target Recruitment: 12

Inclusion Criteria

≥ 5 years of age

Lingual microcystic lymphatic malformation of any stage (Wiegand 2009) assessed by clinical examination and head-and-neck MRI imaging prior to study enrolment, with or without underlying syndromic malformation (CLAPO for instance)

Participants covered by or having the rights to social security

Written informed consent obtained from participant and participant’s legal representative if participant is under 18

Ability for participant to comply with the requirements of the study

Compliance with the French mandatory immunization program

Exclusion Criteria

Patients with a lymphatic malformation requiring a continued background therapy (involving deep organs)

Known allergy to one of the components of the sirolimus solution

Soy bean or Peanut allergy

Pregnant or breastfeeding women

Women of child-bearing potential (including teenagers) not using a reliable contraceptive method until the end of the study and three month after the end of the study or sirolimus discontinuation

Already involved in another therapeutic trial

Secondary lymphatic malformations (lymphangiectasia post-radiotherapy, etc)

Previous treatment with systemic or topical mTOR inhibitors within 6 months before inclusion (half-life of oral sirolimus is 60 hours in adults according to Rapamune ® Summary of Product Characteristics)

Previous treatment with oral or topical steroids within 10 days before inclusion (half-life of corticosteroids is 12-36 hours)

Immunosuppression (immunosuppressive disease or immunosuppressive treatment)

Ongoing neoplasia

Active chronic infectious disease (HBV, HCV, HIV, etc)

Local necrosis

Local fungal, viral (HSV, VZV, etc) or bacterial infection on the site of the LMLM (based on clinical examination)

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The primary outcome will consist in the evaluation of global severity of the LMLM using PGA (Physical Global Assessment) 0 to 5 score, by three independent blinded experts, on monthly standardized photographs. A 1-point improvement versus baseline in PGA scale would already have a clinical relevance. Our primary analysis will focus on change in PGA after topical application of Sirolimus for 12 weeks		The primary outcome will consist in the evaluation of global severity of the LMLM using PGA (Physical Global Assessment) 0 to 5 score, by three independent blinded experts, on monthly standardized photographs. A 1-point improvement versus baseline in PGA scale would already have a clinical relevance. Our primary analysis will focus on change in PGA after topical application of Sirolimus for 12 weeks

Secondary Outcome Measures

Name	Time	Method
Investigator-assessed PGA at weeks 0, 4, 8, 12, 16, 20 and 24		Investigator-assessed PGA at weeks 0, 4, 8, 12, 16, 20 and 24
Assessment by the patient regarding severity of oozing, bleeding, sialorrhea, eating impairment, taste modification, aesthetic impairment, pain and global discomfort, each using a numeric scale from 0 to 10 (0: clear, 10: very severe), at weeks 0, 4, 8, 12, 16, 20 and 24		Assessment by the patient regarding severity of oozing, bleeding, sialorrhea, eating impairment, taste modification, aesthetic impairment, pain and global discomfort, each using a numeric scale from 0 to 10 (0: clear, 10: very severe), at weeks 0, 4, 8, 12, 16, 20 and 24
Global evolution compared to baseline, assessed by the patient from -10 to 10 (-10 = severe worsening, 0 = no change, 10 = complete recovery), at weeks 4, 8, 12, 16, 20 and 24		Global evolution compared to baseline, assessed by the patient from -10 to 10 (-10 = severe worsening, 0 = no change, 10 = complete recovery), at weeks 4, 8, 12, 16, 20 and 24
Global Quality of life assessment (DLQI or children’s DLQI for minors aged 5 to 16), at baseline, time of switch to treatment and W24		Global Quality of life assessment (DLQI or children’s DLQI for minors aged 5 to 16), at baseline, time of switch to treatment and W24
Measurement of the lesion (length, width, thickness) by the investigator, at baseline, time of switch to treatment and W24		Measurement of the lesion (length, width, thickness) by the investigator, at baseline, time of switch to treatment and W24
Time to obtain optimal results		Time to obtain optimal results
Safety: Assessment of tolerance of topical sirolimus: record of local adverse events at each visit, before and after the patient has crossed over to the intervention		Safety: Assessment of tolerance of topical sirolimus: record of local adverse events at each visit, before and after the patient has crossed over to the intervention
Safety : record of general adverse events at each visit, before and after the patient has crossed over to the intervention, physical examination, systolic and diastolic blood pressure measurement		Safety : record of general adverse events at each visit, before and after the patient has crossed over to the intervention, physical examination, systolic and diastolic blood pressure measurement
Safety: Assessment of sirolimus blood passage by measuring residual sirolimus blood concentration: after 4 weeks of treatment, then 8 weeks, then every 8 weeks until W24		Safety: Assessment of sirolimus blood passage by measuring residual sirolimus blood concentration: after 4 weeks of treatment, then 8 weeks, then every 8 weeks until W24
Safety: Evaluation of biological safety at weeks 8, 16 and 24 of exposure compared to baseline (we will perform biological measurements that are required for assessing safety of oral sirolimus: complete blood count, liver (ASAT, ALAT, GGT) and renal (serum creatinine) functions, lipids [cholesterol i.e. total cholesterol, HDL and LDL calculation according to Friedwald's formula and triglycerides] and glycaemia)		Safety: Evaluation of biological safety at weeks 8, 16 and 24 of exposure compared to baseline (we will perform biological measurements that are required for assessing safety of oral sirolimus: complete blood count, liver (ASAT, ALAT, GGT) and renal (serum creatinine) functions, lipids [cholesterol i.e. total cholesterol, HDL and LDL calculation according to Friedwald's formula and triglycerides] and glycaemia)

Trial Locations

Locations (3): Centre Hospitalier Regional Universitaire De Tours
🇫🇷
Tours, France
Hopital Necker Enfants Malades
🇫🇷
Paris, France
Centre Hospitalier Universitaire D Orleans
🇫🇷
Orleans Cedex 2, France
Centre Hospitalier Regional Universitaire De Tours
🇫🇷Tours, France
Annabel MARUANI
Site contact
0247479076
annabel.maruani@univ-tours.fr