Clinical trial NCT03243019: Efficacy of Rapamycin in the Treatment of Cervico-facial Lymphatic Malformations
Official title: Evaluation of the Efficacy of Rapamycin in the Treatment of Cervico-facial Lymphatic Malformations of Poor Prognosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Lymphatic Malformation
Pediatric
Keywords: cervico-facial
rapamycin
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
First posted: 2017-08-08
Enrollment: 28
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Response rate to rapamycin
timeFrame: At 3 months
Secondary outcomes:
measure: Kinetic of rapamycin response
timeFrame: At 3, 6 and 12 months
measure: Efficacy of rapamycin on clinical symptoms
timeFrame: At 3, 6 and 12 months
measure: Pediatric Quality of Life Inventory (PedsQL 4) Scales
timeFrame: Baseline, at 3, 6 and 12 months
measure: Biological response to rapamycin
timeFrame: Baseline and at 6 months
measure: Rapamycin side effects
timeFrame: Monthly during 1 years
Other outcomes:
Locations:
city: Lille
country: France
facility: Hôpital Jeanne de Flandres, CHU
city: Paris
country: France
facility: Hu Robert Debre Aphp - Paris
Study officials:
affiliation: University Hospital, Lille
name: Pierre Fayoux, MD
role: PRINCIPAL_INVESTIGATOR
References: