Lymphatic Malformation, Pediatric
Conditions
Keywords
cervico-facial, rapamycin
Brief summary
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.
Interventions
DRUGrapamycin
oral administration
DEVICEMRI
cervicofacial MRI
BIOLOGICALRapamycin dosage
Biological dosage of Rapamycin level
Sponsors
University Hospital, Lille
Ministry of Health, France
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 18 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response rate to rapamycin | At 3 months | Volumetric assessment by MRI. A response is considered as positive if volume decrease is superior to 1/5th of the initial volume. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Kinetic of rapamycin response | At 3, 6 and 12 months | MRI assessment of the volume |
| Efficacy of rapamycin on clinical symptoms | At 3, 6 and 12 months | Clinical and fiberscopy evaluation by scoring |
| Pediatric Quality of Life Inventory (PedsQL 4) Scales | Baseline, at 3, 6 and 12 months | Assesses health-related quality of life among children with chronic and acute diseases |
| Biological response to rapamycin | Baseline and at 6 months | biological effect of mTOR blockage by measuring pAKT, p70S6 kinase, pMEK, and VEGF C, VEGFR3 |
| Rapamycin side effects | Monthly during 1 years | Side effect assessment using the NCI-CTC 3.0 scale |
Countries
France
Contacts
CONTACTPierre Fayoux, MD
PRINCIPAL_INVESTIGATORPierre Fayoux, MD
University Hospital, Lille
Outcome results
None listed