<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/NCT03271281</url>
  </required_header>
  <id_info>
    <org_study_id>AK2017-2</org_study_id>
    <secondary_id>2017-002512-14</secondary_id>
    <nct_id>NCT03271281</nct_id>
  </id_info>
  <brief_title>PET/CT Imaging of Angiogenesis in Patients With Neuroendocrine Tumors Using 68Ga-NODAGA-E[c(RGDyK)]2</brief_title>
  <official_title>PET/CT Imaging of Angiogenesis in Patients With Neuroendocrine Tumors Using 68Ga-NODAGA-E[c(RGDyK)]2</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rigshospitalet, Denmark</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rigshospitalet, Denmark</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>
      The aim of this non-randomised, prospective study is to investigate the applicability and&#xD;
      prognostic value of angiogenesis PET/CT with the radioligand 68Ga-NODAGA- E[c(RGDyK)]2 in&#xD;
      patients with neuroendocrine tumors (NETs).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The radioligand 68Ga-NODAGA- E[c(RGDyK)]2 targets the Arg-Gly-Asp (RGD) sequence known to&#xD;
      bind with the αvβ3 integrin that is expressed on the surface of angiogenic blood vessels or&#xD;
      tumor cells. The radioligand can be used to visualize tumor angiogenesis using PET/CT.&#xD;
&#xD;
      A total of 120 NET patients will be subjected to an angiogenesis-PET/CT scan. Follow-up will&#xD;
      be performed (from the time of the angiogenesis PET/CT) at 6 months for disease specific&#xD;
      survival (DSS) and a 1 year follow-up for PFS and OS. The uptake of 68Ga-NODAGA-E[c(RGDyK)]2&#xD;
      (Standardized Uptake Values, SUVmax) in tumor lesions will be quantified as Standardized&#xD;
      Uptake Values (SUVmax/SUVmean) and compared with PFS, DSS and OS (dichotomized above/below&#xD;
      median SUVmax and analyzed by Kaplan-Meier).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 4, 2017</start_date>
  <completion_date type="Actual">December 31, 2021</completion_date>
  <primary_completion_date type="Actual">December 31, 2021</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>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Angiogenesis PET/CT imaging of patients with neuroendocrine tumors</measure>
    <time_frame>1 hour</time_frame>
    <description>The radioligand 68Ga-NODAGA-E[c(RGDyK)]2 can be used to visualize neuroendocrine tumors (grade G1-G3)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Angiogenesis PET/CT progonostic factor for progression free survival</measure>
    <time_frame>12 months</time_frame>
    <description>The uptake of the 68Ga-NODAGA-E[c(RGDyK)]2 in neuroendocrine tumor lesions (quantified as Standard Uptake Values) is associated with progression free survival (PFS) neuroendocrine tumors (grade G1-G3)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Angiogenesis PET/CT prognostic factor for overall and disease specific survival</measure>
    <time_frame>12 months</time_frame>
    <description>The uptake of the 68Ga-NODAGA-E[c(RGDyK)]2 in neuroendocrine tumor lesions (quantified as Standard Uptake Values) is associated with overall and disease specific free survival (PFS) neuroendocrine tumors (grade G1-G3)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Target validation of angiogenesis PET/CT</measure>
    <time_frame>2 weeks</time_frame>
    <description>Uptake of 68Ga-NODAGA-E[c(RGDyK)]2 correlates directly to gene expression of angiogenesis markers αvβ3 integrin and VEGF-A in tumor tissue obtained by biopsies or planned surgery (&lt;2 weeks before/after angiogenesis PET/CT)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">113</enrollment>
  <condition>Neuroendocrine Tumors</condition>
  <arm_group>
    <arm_group_label>Experimental: Angiogenesis PET/CT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>One injection of the radioligand 68Ga-NODAGA-E[c(RGDyK)]2 followed by PET/CT</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>One injection of 68Ga-NODAGA-E[c(RGDyK)]2</intervention_name>
    <description>One injection of 68Ga-NODAGA-E[c(RGDyK)]2</description>
    <arm_group_label>Experimental: Angiogenesis PET/CT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>PET/CT</intervention_name>
    <description>Following injection of 68Ga-NODAGA-E[c(RGDyK)]2 the patients will be subjected to whole body PET/CT</description>
    <arm_group_label>Experimental: Angiogenesis PET/CT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosed with gastro-entero-pancreatic Neuroendocrine Tumors (GEP-NET; grade: G1-G3)&#xD;
             or broncho-pulmonary NET.&#xD;
&#xD;
          -  WHO performance status 0-2&#xD;
&#xD;
          -  Must be able to read and understand the patient information in Danish and to give&#xD;
             informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Breast-feeding&#xD;
&#xD;
          -  Weight more than the maximum weight limit for the PET/CT bed of the scanner (140 kg)&#xD;
&#xD;
          -  History of allergic reaction attributable to compounds of similar chemical or biologic&#xD;
             composition to 68Ga-NODAGA-E[c(RGDyK)]2&#xD;
&#xD;
          -  In case of broncho-pulmonary NET, the subtype must not be small cell lung cancer&#xD;
             (SCLC)&#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>Esben Carlsen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rigshospitalet, Denmark</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet</name>
      <address>
        <city>Copenhagen</city>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>August 31, 2017</study_first_submitted>
  <study_first_submitted_qc>August 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 5, 2017</study_first_posted>
  <last_update_submitted>June 28, 2022</last_update_submitted>
  <last_update_submitted_qc>June 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 30, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Rigshospitalet, Denmark</investigator_affiliation>
    <investigator_full_name>Esben Carlsen</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <keyword>68Ga-NODAGA-E[c(RGDyK)]2</keyword>
  <keyword>Angiogenesis PET/CT</keyword>
  <keyword>Neuroendocrine tumors</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neuroendocrine Tumors</mesh_term>
  </condition_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/NCT03271281
org study id: AK2017-2
secondary id: 2017-002512-14
nct id: NCT03271281
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The aim of this non-randomised, prospective study is to investigate the applicability and
      prognostic value of angiogenesis PET/CT with the radioligand 68Ga-NODAGA- E[c(RGDyK)]2 in
      patients with neuroendocrine tumors (NETs).
The radioligand 68Ga-NODAGA- E[c(RGDyK)]2 targets the Arg-Gly-Asp (RGD) sequence known to
      bind with the αvβ3 integrin that is expressed on the surface of angiogenic blood vessels or
      tumor cells. The radioligand can be used to visualize tumor angiogenesis using PET/CT.

      A total of 120 NET patients will be subjected to an angiogenesis-PET/CT scan. Follow-up will
      be performed (from the time of the angiogenesis PET/CT) at 6 months for disease specific
      survival (DSS) and a 1 year follow-up for PFS and OS. The uptake of 68Ga-NODAGA-E[c(RGDyK)]2
      (Standardized Uptake Values, SUVmax) in tumor lesions will be quantified as Standardized
      Uptake Values (SUVmax/SUVmean) and compared with PFS, DSS and OS (dichotomized above/below
      median SUVmax and analyzed by Kaplan-Meier).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Angiogenesis PET/CT imaging of patients with neuroendocrine tumors
time frame: 1 hour
description: The radioligand 68Ga-NODAGA-E[c(RGDyK)]2 can be used to visualize neuroendocrine tumors (grade G1-G3)
measure: Angiogenesis PET/CT progonostic factor for progression free survival
time frame: 12 months
description: The uptake of the 68Ga-NODAGA-E[c(RGDyK)]2 in neuroendocrine tumor lesions (quantified as Standard Uptake Values) is associated with progression free survival (PFS) neuroendocrine tumors (grade G1-G3)
measure: Angiogenesis PET/CT prognostic factor for overall and disease specific survival
time frame: 12 months
description: The uptake of the 68Ga-NODAGA-E[c(RGDyK)]2 in neuroendocrine tumor lesions (quantified as Standard Uptake Values) is associated with overall and disease specific free survival (PFS) neuroendocrine tumors (grade G1-G3)
measure: Target validation of angiogenesis PET/CT
time frame: 2 weeks
description: Uptake of 68Ga-NODAGA-E[c(RGDyK)]2 correlates directly to gene expression of angiogenesis markers αvβ3 integrin and VEGF-A in tumor tissue obtained by biopsies or planned surgery (<2 weeks before/after angiogenesis PET/CT)
arm group label: Experimental: Angiogenesis PET/CT
arm group type: Experimental
description: One injection of the radioligand 68Ga-NODAGA-E[c(RGDyK)]2 followed by PET/CT
intervention type: Drug
intervention name: One injection of 68Ga-NODAGA-E[c(RGDyK)]2
description: One injection of 68Ga-NODAGA-E[c(RGDyK)]2
arm group label: Experimental: Angiogenesis PET/CT
intervention type: Device
intervention name: PET/CT
description: Following injection of 68Ga-NODAGA-E[c(RGDyK)]2 the patients will be subjected to whole body PET/CT
arm group label: Experimental: Angiogenesis PET/CT
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Esben Carlsen, MD
role: Principal Investigator
affiliation: Rigshospitalet, Denmark
facility: 
country: Denmark
responsible party type: Principal Investigator
investigator affiliation: Rigshospitalet, Denmark
investigator full name: Esben Carlsen
investigator title: MD
mesh term: Neuroendocrine Tumors