Lingual microcystic lymphatic malformations (LMLM) in children and adults MedDRA version: 20.0 Level: LLT Classification code 10003229 Term: Arteriovenous malformations System Organ Class: 100000004850
Conditions
Interventions
Trade Name: RAPAMUNE
Product Name: Sirolimus 1mg/mL
Product Code: L04AA10
Pharmaceutical Form: Oral liquid
Sponsors
CHRU TOURS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients = 5 years - Lingual microcystic lymphatic malformation Wiegand stage I or IIa (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 Are the trial subjects under 18? yes Number of subjects for this age range: 12 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: -Patients with a lymphatic malformation requiring a continued background therapy (involving deep organs) -Secondary lymphatic malformations (lymphangiectasia post-radiotherapy, etc) -Previous treatment with systemic or topical mTOR inhibitors within 12 months before inclusion (half-life of oral sirolimus is 60 days in adults). -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)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 -Already involved in another therapeutic trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the efficacy and safety of a 1mg/mL sirolimus solution applied once daily on mild to moderate lingual microcystic lymphatic malformation in children and adults after 4, 8, 12, 16, 20 and 24 weeks of treatment as compared to usual care (no treatment).;Secondary Objective: evaluate patient-reported global efficacy of the application of 1mg/mL sirolimus solution on mild to moderate lingual microcystic lymphatic malformation in children and adults. -Evaluate patient-reported specific efficacy of the application of 1mg/mL sirolimus solution on mild to moderate LMLM in children and adults, versus usual care, on the following symptoms: oozing, bleeding, sialorrhea, eating impairment, taste modification, aesthetic impairment, pain and global discomfort. -Evaluate quality of life of patients before and after treatment with topical sirolimus. -Assess time to optimal results. - Safety: by measuring systemic passage of sirolimus and assessing tolerance (local tolerance and general safety data). ;Primary end point(s): 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 ;Timepoint(s) of evaluation of this end point: At week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - 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. - Global evolution 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. - Measurement of the lesion (length, width, thickness) by the investigator, at baseline, time of switch to treatment and W24. - Time to obtain optimal results - Safety: - Assessment of tolerance of topical sirolimus: record of local side effects at each visit after the patient has crossed over to the intervention - General side effects, physical examination, systolic and diastolic blood pressure measurement. - 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 - 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 and triglycerides] and glycaemia) ;Timepoint(s) of evaluation of this end point: - 1. at weeks 0, 4, 8, 12, 16, 20 and 24 -2. at weeks 0, 4, 8, 12, 16, 20 and 24. -3 at weeks 4, 8, 12, 16, 20 and 24. -QOL at baseline, time of switch to treatment and W24. -Measurement of the lesion at baseline, time of switch to treatment and W24. -Time to obtain optimal results - Assessment of tolerance of topical sirolimus: record of local side effects at each visit after the patien | — |
Countries
France
Contacts
Public ContactARC DRCI - Wiebe de JONG
CHRU TOURS
Outcome results
None listed