<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03243019</url>
  </required_header>
  <id_info>
    <org_study_id>2012_67</org_study_id>
    <secondary_id>2013-002800-15</secondary_id>
    <nct_id>NCT03243019</nct_id>
  </id_info>
  <brief_title>Efficacy of Rapamycin in the Treatment of Cervico-facial Lymphatic Malformations</brief_title>
  <acronym>RAPAMALYMPH</acronym>
  <official_title>Evaluation of the Efficacy of Rapamycin in the Treatment of Cervico-facial Lymphatic Malformations of Poor Prognosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Lille</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ministry of Health, France</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Lille</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate the efficacy of Rapamycin in extended cervicofacial lymphatic malformations in&#xD;
      pediatric patients. Rapamycin is administered oral for a 6 month period.&#xD;
&#xD;
      The success rate is determined by volume reduction superior to 1/5e of the initial volume&#xD;
      measured by MRI, impact on QOL and reduction of bleeding in case of mucosal involvement.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 25, 2018</start_date>
  <completion_date type="Anticipated">February 2025</completion_date>
  <primary_completion_date type="Anticipated">February 2025</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Response rate to rapamycin</measure>
    <time_frame>At 3 months</time_frame>
    <description>Volumetric assessment by MRI. A response is considered as positive if volume decrease is superior to 1/5th of the initial volume.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Kinetic of rapamycin response</measure>
    <time_frame>At 3, 6 and 12 months</time_frame>
    <description>MRI assessment of the volume</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy of rapamycin on clinical symptoms</measure>
    <time_frame>At 3, 6 and 12 months</time_frame>
    <description>Clinical and fiberscopy evaluation by scoring</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pediatric Quality of Life Inventory (PedsQL 4) Scales</measure>
    <time_frame>Baseline, at 3, 6 and 12 months</time_frame>
    <description>Assesses health-related quality of life among children with chronic and acute diseases</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biological response to rapamycin</measure>
    <time_frame>Baseline and at 6 months</time_frame>
    <description>biological effect of mTOR blockage by measuring pAKT, p70S6 kinase, pMEK, and VEGF C, VEGFR3</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rapamycin side effects</measure>
    <time_frame>Monthly during 1 years</time_frame>
    <description>Side effect assessment using the NCI-CTC 3.0 scale</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">28</enrollment>
  <condition>Lymphatic Malformation</condition>
  <condition>Pediatric</condition>
  <arm_group>
    <arm_group_label>SIROLIMUS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>rapamycin</intervention_name>
    <description>oral administration</description>
    <arm_group_label>SIROLIMUS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>MRI</intervention_name>
    <description>cervicofacial MRI</description>
    <arm_group_label>SIROLIMUS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Rapamycin dosage</intervention_name>
    <description>Biological dosage of Rapamycin level</description>
    <arm_group_label>SIROLIMUS</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient from 0 to 18 years of age, presenting with poly-cystic suprahyoid or&#xD;
             mediastinal lymphatic.&#xD;
&#xD;
          -  with chronic pain or functional respiratory or swallowing impairment with a CDS score&#xD;
             &lt; 8&#xD;
&#xD;
          -  Curative treatment is not possible or associated with a high risk of morbidity&#xD;
             ,mortality and functional and cosmetic impairment&#xD;
&#xD;
          -  Karnofsky Score (&gt; 10 years of age) or Lansky score (≤10 years of age) &gt; 50%&#xD;
&#xD;
          -  Biology&#xD;
&#xD;
               -  Neutrophils count≥1.0 x 109/L&#xD;
&#xD;
               -  Platelets count ≥ 100 x 109/L&#xD;
&#xD;
               -  Hemoglobin ≥ 8 g/dL&#xD;
&#xD;
               -  Bilirubin ≤ 1,5 ULN&#xD;
&#xD;
               -  Transaminases &lt; 2,5 ULN&#xD;
&#xD;
               -  Serum albumin ≥ 2 g/dL.&#xD;
&#xD;
               -  LDL cholesterol &lt;160 mg/dL&#xD;
&#xD;
               -  Triglycerides &lt; 150 mg/dL&#xD;
&#xD;
          -  Negative test of pregnancy if relevant&#xD;
&#xD;
          -  Social security affiliation&#xD;
&#xD;
          -  At least 2 months after a previous procedure on the malformation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Non-respect of inclusion criteria&#xD;
&#xD;
          -  Other immunosuppressive therapy or long-term general corticosteroid therapy without a&#xD;
             28-day washout period&#xD;
&#xD;
          -  renal failure&#xD;
&#xD;
          -  Liver failure&#xD;
&#xD;
          -  Digestive disease leading to rapamycin malabsorption&#xD;
&#xD;
          -  uncontrolled or severe infectious disease&#xD;
&#xD;
          -  Patients requiring treatment interfering with CYP3A4 isoenzyme (rifampicin, rifabutin,&#xD;
             carbamazepine, phenobarbital, phenytoin) or inhibiting CYP3A4 isoenzyme's activity&#xD;
             (ketoconazole, voriconazole, itraconazole, telithromycin, clarithromycin, Diltiazem,&#xD;
             Verapamil, nicardipine, clotrimazole, fluconazole , troleandomycin, bromocriptine,&#xD;
             cimetidine, danazol, protease inhibitors) -patients requiring treatment by cisapride&#xD;
             and metoclopramide&#xD;
&#xD;
          -  Concomitant administration of mTOR inhibitor&#xD;
&#xD;
          -  Peanuts or soya allergy&#xD;
&#xD;
          -  Impossibility to receive informed consent&#xD;
&#xD;
          -  Absence of social security affiliation&#xD;
&#xD;
          -  refusal to sign consent&#xD;
&#xD;
          -  Ongoing pregnancy or breastfeeding&#xD;
&#xD;
          -  refusal to participate&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pierre Fayoux, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Lille</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Pierre Fayoux, MD</last_name>
    <phone>3 20 44 50 67</phone>
    <phone_ext>+33</phone_ext>
    <email>pierre.fayoux@chru-lille.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hôpital Jeanne de Flandres, CHU</name>
      <address>
        <city>Lille</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>pierre Fayoux, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hu Robert Debre Aphp - Paris</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>August 1, 2017</study_first_submitted>
  <study_first_submitted_qc>August 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 8, 2017</study_first_posted>
  <last_update_submitted>August 16, 2022</last_update_submitted>
  <last_update_submitted_qc>August 16, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 17, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>cervico-facial</keyword>
  <keyword>rapamycin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphangioma</mesh_term>
    <mesh_term>Lymphatic Abnormalities</mesh_term>
    <mesh_term>Congenital Abnormalities</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sirolimus</mesh_term>
    <mesh_term>Temsirolimus</mesh_term>
    <mesh_term>MTOR Inhibitors</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03243019
org study id: 2012_67
secondary id: 2013-002800-15
nct id: NCT03243019
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Response rate to rapamycin
time frame: At 3 months
description: Volumetric assessment by MRI. A response is considered as positive if volume decrease is superior to 1/5th of the initial volume.
measure: Kinetic of rapamycin response
time frame: At 3, 6 and 12 months
description: MRI assessment of the volume
measure: Efficacy of rapamycin on clinical symptoms
time frame: At 3, 6 and 12 months
description: Clinical and fiberscopy evaluation by scoring
measure: Pediatric Quality of Life Inventory (PedsQL 4) Scales
time frame: Baseline, at 3, 6 and 12 months
description: Assesses health-related quality of life among children with chronic and acute diseases
measure: Biological response to rapamycin
time frame: Baseline and at 6 months
description: biological effect of mTOR blockage by measuring pAKT, p70S6 kinase, pMEK, and VEGF C, VEGFR3
measure: Rapamycin side effects
time frame: Monthly during 1 years
description: Side effect assessment using the NCI-CTC 3.0 scale
arm group label: SIROLIMUS
arm group type: Experimental
intervention type: Drug
intervention name: rapamycin
description: oral administration
arm group label: SIROLIMUS
intervention type: Device
intervention name: MRI
description: cervicofacial MRI
arm group label: SIROLIMUS
intervention type: Biological
intervention name: Rapamycin dosage
description: Biological dosage of Rapamycin level
arm group label: SIROLIMUS
criteria: 
gender: All
minimum age: N/A
maximum age: 18 Years
healthy volunteers: No
last name: Pierre Fayoux, MD
role: Principal Investigator
affiliation: University Hospital, Lille
last name: Pierre Fayoux, MD
phone: 3 20 44 50 67
phone ext: +33
email: pierre.fayoux@chru-lille.fr
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
country: France
responsible party type: Sponsor
mesh term: Lymphangioma
mesh term: Lymphatic Abnormalities
mesh term: Congenital Abnormalities
mesh term: Sirolimus
mesh term: Temsirolimus
mesh term: MTOR Inhibitors
sharing ipd: No