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

Pediatric Clinical Trial

— RAPAMALYMPH  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03243019
• Other study ID #: 2012_67
• Secondary ID: 2013-002800-15
• Status: Recruiting
• Phase: Phase 2
• Start date: June 25, 2018
• Est. completion date: February 2025

Study information

• Verified date: August 2022
• Source: University Hospital, Lille
• Contact: Pierre Fayoux, MD
• Phone: 3 20 44 50 67
• Email: pierre.fayoux[@]chru-lille.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 28
• Est. completion date: February 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Congenital Abnormalities
• Lymphangioma
• Lymphatic Abnormalities
• Lymphatic Malformation
• Pediatric

Intervention

Drug:
• rapamycin
oral administration

Device:
• MRI
cervicofacial MRI

Biological:
• Rapamycin dosage
Biological dosage of Rapamycin level

Locations

Country	Name	City	State
France	Hôpital Jeanne de Flandres, CHU	Lille
France	Hu Robert Debre Aphp - Paris	Paris

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Lille	Ministry of Health, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Kinetic of rapamycin response	MRI assessment of the volume	At 3, 6 and 12 months
Secondary	Efficacy of rapamycin on clinical symptoms	Clinical and fiberscopy evaluation by scoring	At 3, 6 and 12 months
Secondary	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
Secondary	Biological response to rapamycin	biological effect of mTOR blockage by measuring pAKT, p70S6 kinase, pMEK, and VEGF C, VEGFR3	Baseline and at 6 months
Secondary	Rapamycin side effects	Side effect assessment using the NCI-CTC 3.0 scale	Monthly during 1 years