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

Phase 2

Recruiting

• Conditions: Lymphatic Malformation; Pediatric
• Interventions: Drug: rapamycin; Device: MRI; Biological: Rapamycin dosage

• Registration Number: NCT03243019
• Lead Sponsor: University Hospital, Lille

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-08-01
• Study First Submitted QC: 2017-08-03
• Study First Posted: 2017-08-08
• Study Start: 2018-06-25
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-16
• Last Update Posted: 2022-08-17
• Primary Completion: 2025-02
• Study Completion: 2025-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 28

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
SIROLIMUS	MRI	-
SIROLIMUS	Rapamycin dosage	-
SIROLIMUS	rapamycin	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Kinetic of rapamycin response	At 3, 6 and 12 months	MRI assessment of the volume
Rapamycin side effects	Monthly during 1 years	Side effect assessment using the NCI-CTC 3.0 scale
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

Trial Locations

Locations (2)

Hôpital Jeanne de Flandres, CHU; 🇫🇷 Lille, France

Hu Robert Debre Aphp - Paris; 🇫🇷 Paris, France