Efficacy of Rapamycin in the Treatment of Cervico-facial Lymphatic Malformations

Study Overview
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Brief Summary
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To evaluate the efficacy of Rapamycin in extended cervicofacial lymphatic malformations in pediatric patients. Rapamycin is administered oral for a 6 month period. The success rate is determined by volume reduction superior to 1/5e of the initial volume measured by MRI, impact on QOL and reduction of bleeding in case of mucosal involvement.

Official Title
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Evaluation of the Efficacy of Rapamycin in the Treatment of Cervico-facial Lymphatic Malformations of Poor Prognosis

Conditions
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Lymphatic Malformation, Pediatric

Intervention / Treatment
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* Drug: rapamycin
* Device: MRI
* Biological: Rapamycin dosage


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient from 0 to 18 years of age, presenting with poly-cystic suprahyoid or mediastinal lymphatic. with chronic pain or functional respiratory or swallowing impairment with a CDS score < 8 Curative treatment is not possible or associated with a high risk of morbidity ,mortality and functional and cosmetic impairment Karnofsky Score (> 10 years of age) or Lansky score (≤10 years of age) > 50% Biology Neutrophils count≥1.0 x 109/L Platelets count ≥ 100 x 109/L Hemoglobin ≥ 8 g/dL Bilirubin ≤ 1,5 ULN Transaminases < 2,5 ULN Serum albumin ≥ 2 g/dL. LDL cholesterol <160 mg/dL Triglycerides < 150 mg/dL Negative test of pregnancy if relevant Social security affiliation At least 2 months after a previous procedure on the malformation Exclusion Criteria: Non-respect of inclusion criteria Other immunosuppressive therapy or long-term general corticosteroid therapy without a 28-day washout period renal failure Liver failure Digestive disease leading to rapamycin malabsorption uncontrolled or severe infectious disease Patients requiring treatment interfering with CYP3A4 isoenzyme (rifampicin, rifabutin, carbamazepine, phenobarbital, phenytoin) or inhibiting CYP3A4 isoenzyme's activity (ketoconazole, voriconazole, itraconazole, telithromycin, clarithromycin, Diltiazem, Verapamil, nicardipine, clotrimazole, fluconazole , troleandomycin, bromocriptine, cimetidine, danazol, protease inhibitors) -patients requiring treatment by cisapride and metoclopramide Concomitant administration of mTOR inhibitor Peanuts or soya allergy Impossibility to receive informed consent Absence of social security affiliation refusal to sign consent Ongoing pregnancy or breastfeeding refusal to participate

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SIROLIMUS<br> | Drug: rapamycin<br>* oral administration<br>Device: MRI<br>* cervicofacial MRI<br>Biological: Rapamycin dosage<br>* Biological dosage of Rapamycin level<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate to rapamycin | Volumetric assessment by MRI. A response is considered as positive if volume decrease is superior to 1/5th of the initial volume. | At 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kinetic of rapamycin response | MRI assessment of the volume | At 3, 6 and 12 months | 
| Efficacy of rapamycin on clinical symptoms | Clinical and fiberscopy evaluation by scoring | At 3, 6 and 12 months | 
| Pediatric Quality of Life Inventory (PedsQL 4) Scales | Assesses health-related quality of life among children with chronic and acute diseases | Baseline, at 3, 6 and 12 months | 
| Biological response to rapamycin | biological effect of mTOR blockage by measuring pAKT, p70S6 kinase, pMEK, and VEGF C, VEGFR3 | Baseline and at 6 months | 
| Rapamycin side effects | Side effect assessment using the NCI-CTC 3.0 scale | Monthly during 1 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cervico-facial, rapamycin