Efficacy of Rapamycin in the Treatment of Cervico-facial Lymphatic Malformations (RAPAMALYMPH)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Pediatric; Lymphatic Malformation
• Intervention / Treatment: Drug: rapamycin; Device: MRI; Biological: Rapamycin dosage

• Study Type: Interventional
• Enrollment (Anticipated): 28
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Pierre Fayoux, MD; Phone Number: +33 3 20 44 50 67; Email: pierre.fayoux@chru-lille.fr

Study Locations

• France
  • Lille, France
    • Recruiting
    • Hôpital Jeanne de Flandres, CHU
    • Principal Investigator: pierre Fayoux, MD
  • Paris, France
    • Recruiting
    • Hu Robert Debre Aphp - Paris

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 16 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SIROLIMUS	Drug: rapamycin; oral administration; Device: MRI; cervicofacial MRI; Biological: Rapamycin dosage; Biological dosage of Rapamycin level

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Lille
• Collaborators: Ministry of Health, France
• Investigators: Principal Investigator: Pierre Fayoux, MD, University Hospital, Lille

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2018
• Primary Completion (Anticipated): February 1, 2025
• Study Completion (Anticipated): February 1, 2025

Study Registration Dates

• First Submitted: August 1, 2017
• First Submitted That Met QC Criteria: August 3, 2017
• First Posted (Actual): August 8, 2017

Study Record Updates

• Last Update Posted (Actual): August 17, 2022
• Last Update Submitted That Met QC Criteria: August 16, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: rapamycin; cervico-facial
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Lymphatic Diseases; Lymphatic Vessel Tumors; Congenital Abnormalities; Lymphangioma; Lymphatic Abnormalities; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: 2012_67; 2013-002800-15 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No