<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/NCT02248012</url>
  </required_header>
  <id_info>
    <org_study_id>2013-002524-16</org_study_id>
    <nct_id>NCT02248012</nct_id>
  </id_info>
  <brief_title>Everolimus and Temozolomide in Advanced Gastroenteropancreatic Neuroendocrine Carcinoma (G3)</brief_title>
  <official_title>Everolimus and Temozolomide as 1-line Treatment in Advanced Gastroenteropancreatic Neuroendocrine Carcinoma (G3) With a Ki67 of 20-55%</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Haukeland University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Skane University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Copenhagen University Hospital, Denmark</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Rigshospitalet, Denmark</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Uppsala University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Aarhus University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sahlgrenska University Hospital, Sweden</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ullevaal University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Haukeland University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To study the efficacy of everolimus combined with temozolomide as first-line treatment in&#xD;
      advanced gastroenteropancreatic neuroendocrine carcinoma with a Ki67 of 20-55%, measured as&#xD;
      disease control rate (non-progressive disease) at 6 months.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Guidelines for treating advanced gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs)&#xD;
      advocate the use of combination chemotherapy with a platinum-based chemotherapy combined with&#xD;
      etoposide. No other regimen has consistently shown a benefit over this combination. NECs do&#xD;
      not respond to treatments usually applied in other neuroendocrine tumours such as&#xD;
      somatostatin analogues and interferon. In contrast to metastatic neuroendocrine tumours with&#xD;
      a low Ki67, debulking surgery and surgery for liver metastasis is generally not recommended.&#xD;
      Cisplatin /carboplatin and etoposide is established as standard treatment of advanced disease&#xD;
      based on two small retrospective studies showing a response rate between 41- 67% and median&#xD;
      survival of 15-19 months. In the current trial we propose an alternative treatment for a&#xD;
      subgroup of patients with GEP-NEC based on new data, with the intention to improve response&#xD;
      rates and clinical benefit rate without increasing toxicity&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2014</start_date>
  <completion_date type="Actual">December 1, 2019</completion_date>
  <primary_completion_date type="Actual">January 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>Disease control rate</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>During treatment + 30 days</time_frame>
    <description>Especially number of patients with grade 3-4 toxicity.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Time (months) from start of study treatment to death (survival)</measure>
    <time_frame>Average 14 months</time_frame>
    <description>Patients alive at 18 months after last patient entered into the study will be censored.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">38</enrollment>
  <condition>Neuroendocrine Carcinoma</condition>
  <arm_group>
    <arm_group_label>Everolimus/temozolomide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Everolimus 10 mg daily, temozolomide 150 mg/m2 for 7 days every 2 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Everolimus , temozolomide</intervention_name>
    <arm_group_label>Everolimus/temozolomide</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria&#xD;
&#xD;
        Histologically proven neuroendocrine carcinoma with a Ki67 of 20-55%.Primary&#xD;
        gastroenteropancreatic tumor or cancer of unknown primary where metastases are mainly&#xD;
        abdominalMeasurable disease according to RECIST by CT/MR&#xD;
&#xD;
        General conditions:&#xD;
&#xD;
          -  &gt;18 years;&#xD;
&#xD;
          -  WHO/ECOG performance status 0-1.&#xD;
&#xD;
          -  Adequate haematological, renal and hepatic functions:&#xD;
&#xD;
          -  Written informed consent prior to inclusion&#xD;
&#xD;
        Prior therapy:&#xD;
&#xD;
          -  No prior chemotherapy treatment for advanced disease.&#xD;
&#xD;
          -  Adjuvant chemotherapy must have ended &gt; 6 months before inclusion.&#xD;
&#xD;
        Prior or current history:&#xD;
&#xD;
          -  No curatively resectable disease;&#xD;
&#xD;
          -  No other serious illness or medical conditions (including: unstable angina, myocardial&#xD;
             infarction within 6 months, unstable diabetes, immune suppression )&#xD;
&#xD;
        Concomitant treatments :&#xD;
&#xD;
          -  No concomitant (or within 4 weeks before inclusion) administration of any other&#xD;
             experimental drug;&#xD;
&#xD;
          -  No other concurrent anti-cancer therapy.&#xD;
&#xD;
        Other :&#xD;
&#xD;
          -  Not pregnant or breast feeding. Fertile patients must use adequate contraceptives and&#xD;
             fertile females must have a negative pregnancy test.&#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>Halfdan Sorbye, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Haukeland Univ Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Haukeland University Hospital</name>
      <address>
        <city>Bergen</city>
        <zip>5021</zip>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Norway</country>
  </location_countries>
  <reference>
    <citation>Sorbye H, Strosberg J, Baudin E, Klimstra DS, Yao JC. Gastroenteropancreatic high-grade neuroendocrine carcinoma. Cancer. 2014 Sep 15;120(18):2814-23. doi: 10.1002/cncr.28721. Epub 2014 Apr 25.</citation>
    <PMID>24771552</PMID>
  </reference>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>July 24, 2014</study_first_submitted>
  <study_first_submitted_qc>September 19, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <last_update_submitted>December 18, 2019</last_update_submitted>
  <last_update_submitted_qc>December 18, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 19, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Gastroenteropancreatic</keyword>
  <keyword>Neuroendocrine carcinoma</keyword>
  <keyword>Chemotherapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Neuroendocrine</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Everolimus</mesh_term>
    <mesh_term>Temozolomide</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02248012
org study id: 2013-002524-16
nct id: NCT02248012
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
To study the efficacy of everolimus combined with temozolomide as first-line treatment in
      advanced gastroenteropancreatic neuroendocrine carcinoma with a Ki67 of 20-55%, measured as
      disease control rate (non-progressive disease) at 6 months.
Guidelines for treating advanced gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs)
      advocate the use of combination chemotherapy with a platinum-based chemotherapy combined with
      etoposide. No other regimen has consistently shown a benefit over this combination. NECs do
      not respond to treatments usually applied in other neuroendocrine tumours such as
      somatostatin analogues and interferon. In contrast to metastatic neuroendocrine tumours with
      a low Ki67, debulking surgery and surgery for liver metastasis is generally not recommended.
      Cisplatin /carboplatin and etoposide is established as standard treatment of advanced disease
      based on two small retrospective studies showing a response rate between 41- 67% and median
      survival of 15-19 months. In the current trial we propose an alternative treatment for a
      subgroup of patients with GEP-NEC based on new data, with the intention to improve response
      rates and clinical benefit rate without increasing toxicity
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Disease control rate
time frame: 6 months
measure: Number of patients with adverse events
time frame: During treatment + 30 days
description: Especially number of patients with grade 3-4 toxicity.
measure: Time (months) from start of study treatment to death (survival)
time frame: Average 14 months
description: Patients alive at 18 months after last patient entered into the study will be censored.
arm group label: Everolimus/temozolomide
arm group type: Experimental
description: Everolimus 10 mg daily, temozolomide 150 mg/m2 for 7 days every 2 weeks.
intervention type: Drug
intervention name: Everolimus , temozolomide
arm group label: Everolimus/temozolomide
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Halfdan Sorbye, MD
role: Principal Investigator
affiliation: Haukeland Univ Hospital
facility: 
country: Norway
citation: Sorbye H, Strosberg J, Baudin E, Klimstra DS, Yao JC. Gastroenteropancreatic high-grade neuroendocrine carcinoma. Cancer. 2014 Sep 15;120(18):2814-23. doi: 10.1002/cncr.28721. Epub 2014 Apr 25.
PMID: 24771552
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Neuroendocrine
mesh term: Everolimus
mesh term: Temozolomide