<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/NCT01678664</url>
  </required_header>
  <id_info>
    <org_study_id>FFCD 1104</org_study_id>
    <nct_id>NCT01678664</nct_id>
  </id_info>
  <brief_title>Everolimus After (Chemo)Embolization for Liver Metastases From Digestive Endocrine Tumors</brief_title>
  <acronym>EVACEL</acronym>
  <official_title>Everolimus as Treatment After Embolization or Chemoembolization for Liver Metastases From Digestive Endocrine Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Federation Francophone de Cancerologie Digestive</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Federation Francophone de Cancerologie Digestive</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Determine wether 24 months treatment with everolimus prolongs progression free survival rate&#xD;
      (based on a central assessment) after embolisation ou chemoembolisation for liver metastases.&#xD;
&#xD;
        -  H0 a 24 months progression free survival rate less than 35% is unacceptable&#xD;
&#xD;
        -  H1 a 24 months progression free survival rate greater than 35% would show that&#xD;
           everolimus treatment is beneficial, the expected 24 months progression free survival&#xD;
           rate being 50%&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2012</start_date>
  <completion_date type="Actual">April 2019</completion_date>
  <primary_completion_date type="Actual">September 2018</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>Rate of hepatic progression free survival at 24 months</measure>
    <time_frame>24 months</time_frame>
    <description>Hepatic progression free survival rate as defined in RECIST 1.1 (with death considered as progression) during the 24 months of treatment with everolimus (appendix 3).&#xD;
Progression-free survival rate (PFS) (based on the central assessment) according to RECIST v1.1 according to RECIST v1.1 will be defined as the time from the date of inclusion to the date of hepatic progression or death (due to any cause). For patients who are alive with no hepatic progression, it will be defines as the time from the date of inclusion and the date of the last tumor assessment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression free survival rate (hepatic or not) at 24 months</measure>
    <time_frame>24 months</time_frame>
    <description>Progression-free survival rate will be defined as the time from the date of inclusion to the date of disease progression (hepatic or not) evaluated by RECIST V1.1 criteria or death (due to any cause) or the date of the last morphological evaluation for patients who are alive with no disease progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival rate</measure>
    <time_frame>24 months</time_frame>
    <description>Overall survival rate shall be defined as the time from the date of inclusion to the date of death, regardless of the cause of death, or the date of last contact for patients who are alive.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Toxicities treatment</measure>
    <time_frame>24 months</time_frame>
    <description>the toxicities recorded at each monthly visit, described using -CTCAE version 4.0; grade 3 and 4 toxicities will be reviewed;</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">74</enrollment>
  <condition>Neuroendocrine Tumors</condition>
  <condition>Hepatic Metastases</condition>
  <condition>Metastases</condition>
  <arm_group>
    <arm_group_label>embolization or chemoembolization plus everolimus</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After 2 sessions of embolization with microsphere of 100 to 500 µm or chemoembolization with 100 mg of doxorubicine and 10 ml of lipiodol, administered every day, 10 mg of everolimus during 24 months or until progression (hepatic and other site).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Everolimus</intervention_name>
    <description>10 mg per day of everolimus during 24 months or until progression disease</description>
    <arm_group_label>embolization or chemoembolization plus everolimus</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>embolization</intervention_name>
    <description>2 sessions embolization with spheric particles</description>
    <arm_group_label>embolization or chemoembolization plus everolimus</arm_group_label>
    <other_name>spheric particules of 100 to 500 µm</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxorubicin</intervention_name>
    <description>2 sessions chemoembolization with 10 mg of lipiodol with 100 mg of doxorubicine</description>
    <arm_group_label>embolization or chemoembolization plus everolimus</arm_group_label>
    <other_name>Chemoembolization</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Well differentiated (grade 1 and 2 according to WHO classification 2010 appendix 2),&#xD;
             histologically-proven endocrine tumor of the gastrointestinal tract (TENpath review&#xD;
             mandatory),&#xD;
&#xD;
          -  Measurable liver metastasis (or metastases) as defined in RECIST v1.1 that are&#xD;
             unresectable and inaccessible to radiofrequency ablation-type local treatment&#xD;
&#xD;
          -  Hepatic arterial embolization or chemoembolization indicated for tumor size reduction,&#xD;
             confirmed in an multidisciplinary team (MDT) meeting, due to the progressive nature of&#xD;
             the liver metastases (morphological progression during the past 12 months as defined&#xD;
             in RECIST v1.1)&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  WHO performance status ≤ 2&#xD;
&#xD;
          -  No contraindications to embolization or chemoembolization or everolimus&#xD;
&#xD;
          -  Satisfactory laboratory assessments:Neutrophil count ≥ 1.5 x 109/L, platelet count ≥&#xD;
             100 x 109/L, Hb &gt; 10 g/dL, serum bilirubin ≤ 1.5 x the upper limit of normal (ULN),&#xD;
             INR &lt; 1.3 (or &lt; 3 for patients on anticoagulant therapy) ALT and AST ≤ 5 x ULN,&#xD;
             creatinine ≤ 1.5 x ULN, fasting serum cholesterol ≤ 300 mg/dL or 7.75 mmol/L and&#xD;
             triglycerides ≤ 2.5 x ULN (if either or both of these limits are exceeded, the patient&#xD;
             may only be included into the study after institution of appropriate lipid-lowering&#xD;
             therapy)&#xD;
&#xD;
          -  Complete resolution of toxic effects of any prior treatments, or persistence at grade&#xD;
             1 at most (CTCAE version 4.0)&#xD;
&#xD;
          -  Minimum time since previous treatment: 28 days&#xD;
&#xD;
          -  Patient has been informed and has signed an informed consent form, after verification&#xD;
             of the eligibility criteria&#xD;
&#xD;
          -  Patient covered by a French national health insurance scheme&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Duodenopancreatic neuroendocrine tumor&#xD;
&#xD;
          -  Poorly differentiated and/or grade 3 endocrine tumor,&#xD;
&#xD;
          -  Embolization or chemoembolization indicated for symptomatic control only&#xD;
&#xD;
          -  Prior hepatic TACE or embolization&#xD;
&#xD;
          -  Prior treatment with an mTOR inhibitor (somatostatin analogs to control secretion are&#xD;
             permitted)&#xD;
&#xD;
          -  Symptomatic bone metastasis (or metastases)&#xD;
&#xD;
          -  Any uncontrolled progressive disease: hepatic failure, renal failure, respiratory&#xD;
             failure, NYHA class III-IV congestive heart failure, unstable angina, myocardial&#xD;
             infarction, significant arrhythmia&#xD;
&#xD;
          -  Interstitial lung disease&#xD;
&#xD;
          -  Uncontrolled diabetes, defined by HbA1c &gt; 8%&#xD;
&#xD;
          -  Chronic corticosteroid or immunosuppressant therapy&#xD;
&#xD;
          -  Hypersensitivity to everolimus, other rapamycin derivatives, or one of the excipients&#xD;
&#xD;
          -  Major surgery, open biopsy, or significant traumatic lesion during the 28 days prior&#xD;
             to starting the investigational treatment Incompletely healed wound or foreseeable&#xD;
             need for major surgery during the study&#xD;
&#xD;
          -  Contraindication to vascular occlusion procedures: Portal thrombosis, biliodigestive&#xD;
             anastomosis&#xD;
&#xD;
          -  Malignancy during the past 5 years, with the exception of curatively treated basal&#xD;
             cell skin carcinoma or in situ cervical cancer&#xD;
&#xD;
          -  Foreseeable non-compliance&#xD;
&#xD;
          -  Medical, geographic, sociological, psychological, or legal situation that would&#xD;
             preclude the patient from completing the study or signing an informed consent form&#xD;
&#xD;
          -  Pregnant or breast-feeding women&#xD;
&#xD;
          -  Men or women of child-bearing potential not using effective contraception&#xD;
&#xD;
          -  Concurrent participation in another investigational study that could affect the&#xD;
             primary endpoint of this study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Thomas WALTER, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hôpital Edouard Herriot - Lyon</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHU - Hôtel Dieu</name>
      <address>
        <city>Angers</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Avicenne</name>
      <address>
        <city>Bobigny</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Saint André</name>
      <address>
        <city>Bordeaux</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Côte de Nacre</name>
      <address>
        <city>Caen</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU - Estaing</name>
      <address>
        <city>Clermont Ferrand</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Beaujon</name>
      <address>
        <city>Clichy</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre GF Leclerc</name>
      <address>
        <city>Dijon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU - Hôpital François Mitterand</name>
      <address>
        <city>Dijon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Edouard Herriot</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU La Timone</name>
      <address>
        <city>Marseille</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHR</name>
      <address>
        <city>Orléans</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Cochin</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Européen Georges Pompidou</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Robert Debré</name>
      <address>
        <city>Reims</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU</name>
      <address>
        <city>Rouen</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Rangueil</name>
      <address>
        <city>Toulouse</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Trousseau</name>
      <address>
        <city>Tours</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Gustave Roussy</name>
      <address>
        <city>Villejuif</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <results_reference>
    <citation>Walter T, Lepage C, Coriat R, Barbier E, Cadiot G, Caroli-Bosc FX, Aparicio T, Bouhier-Leporrier K, Hentic-Dhome O, Gay F, Dupont-Gossart AC, Duluc M, Lepere C, Lecomte T, Smith D, Petorin C, Di-Fiore F, Ghiringhelli F, Legoux JL, Guimbaud R, Baudin E, Lombard-Bohas C, de Baere T; FFCD 1104 investigators/investigators. Everolimus after hepatic arterial embolisation therapy of metastases from gastrointestinal neuroendocrine tumours: The FFCD 1104-EVACEL-GTE phase II study. Eur J Cancer. 2019 Dec;123:92-100. doi: 10.1016/j.ejca.2019.09.021. Epub 2019 Oct 31.</citation>
    <PMID>31678771</PMID>
  </results_reference>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>August 22, 2012</study_first_submitted>
  <study_first_submitted_qc>August 30, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 5, 2012</study_first_posted>
  <last_update_submitted>March 27, 2020</last_update_submitted>
  <last_update_submitted_qc>March 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 30, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>cancer</keyword>
  <keyword>neuroendocrine tumors</keyword>
  <keyword>gastrointestinal tract</keyword>
  <keyword>metastases</keyword>
  <keyword>liver</keyword>
  <keyword>hepatic</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Neoplasms, Second Primary</mesh_term>
    <mesh_term>Neuroendocrine Tumors</mesh_term>
    <mesh_term>Endocrine Gland Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Everolimus</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>August 10, 2022</submitted>
    <returned>July 10, 2023</returned>
    <submitted>July 11, 2023</submitted>
  </pending_results>
  <!-- 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/NCT01678664
org study id: FFCD 1104
nct id: NCT01678664
lead sponsor: 
has dmc: Yes
Determine wether 24 months treatment with everolimus prolongs progression free survival rate
      (based on a central assessment) after embolisation ou chemoembolisation for liver metastases.

        -  H0 a 24 months progression free survival rate less than 35% is unacceptable

        -  H1 a 24 months progression free survival rate greater than 35% would show that
           everolimus treatment is beneficial, the expected 24 months progression free survival
           rate being 50%
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Rate of hepatic progression free survival at 24 months
time frame: 24 months
description: Hepatic progression free survival rate as defined in RECIST 1.1 (with death considered as progression) during the 24 months of treatment with everolimus (appendix 3).
Progression-free survival rate (PFS) (based on the central assessment) according to RECIST v1.1 according to RECIST v1.1 will be defined as the time from the date of inclusion to the date of hepatic progression or death (due to any cause). For patients who are alive with no hepatic progression, it will be defines as the time from the date of inclusion and the date of the last tumor assessment.
measure: Progression free survival rate (hepatic or not) at 24 months
time frame: 24 months
description: Progression-free survival rate will be defined as the time from the date of inclusion to the date of disease progression (hepatic or not) evaluated by RECIST V1.1 criteria or death (due to any cause) or the date of the last morphological evaluation for patients who are alive with no disease progression.
measure: Overall survival rate
time frame: 24 months
description: Overall survival rate shall be defined as the time from the date of inclusion to the date of death, regardless of the cause of death, or the date of last contact for patients who are alive.
measure: Toxicities treatment
time frame: 24 months
description: the toxicities recorded at each monthly visit, described using -CTCAE version 4.0; grade 3 and 4 toxicities will be reviewed;
arm group label: embolization or chemoembolization plus everolimus
arm group type: Experimental
description: After 2 sessions of embolization with microsphere of 100 to 500 µm or chemoembolization with 100 mg of doxorubicine and 10 ml of lipiodol, administered every day, 10 mg of everolimus during 24 months or until progression (hepatic and other site).
intervention type: Drug
intervention name: Everolimus
description: 10 mg per day of everolimus during 24 months or until progression disease
arm group label: embolization or chemoembolization plus everolimus
intervention type: Device
intervention name: embolization
description: 2 sessions embolization with spheric particles
arm group label: embolization or chemoembolization plus everolimus
other name: spheric particules of 100 to 500 µm
intervention type: Drug
intervention name: Doxorubicin
description: 2 sessions chemoembolization with 10 mg of lipiodol with 100 mg of doxorubicine
arm group label: embolization or chemoembolization plus everolimus
other name: Chemoembolization
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Thomas WALTER, PhD
role: Principal Investigator
affiliation: Hôpital Edouard Herriot - Lyon
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: France
citation: Walter T, Lepage C, Coriat R, Barbier E, Cadiot G, Caroli-Bosc FX, Aparicio T, Bouhier-Leporrier K, Hentic-Dhome O, Gay F, Dupont-Gossart AC, Duluc M, Lepere C, Lecomte T, Smith D, Petorin C, Di-Fiore F, Ghiringhelli F, Legoux JL, Guimbaud R, Baudin E, Lombard-Bohas C, de Baere T; FFCD 1104 investigators/investigators. Everolimus after hepatic arterial embolisation therapy of metastases from gastrointestinal neuroendocrine tumours: The FFCD 1104-EVACEL-GTE phase II study. Eur J Cancer. 2019 Dec;123:92-100. doi: 10.1016/j.ejca.2019.09.021. Epub 2019 Oct 31.
PMID: 31678771
responsible party type: Sponsor
mesh term: Neoplasm Metastasis
mesh term: Neoplasms, Second Primary
mesh term: Neuroendocrine Tumors
mesh term: Endocrine Gland Neoplasms
mesh term: Doxorubicin
mesh term: Everolimus
submitted: August 10, 2022
returned: July 10, 2023
submitted: July 11, 2023