<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/NCT03817307</url>
  </required_header>
  <id_info>
    <org_study_id>USPIO-NECK</org_study_id>
    <nct_id>NCT03817307</nct_id>
  </id_info>
  <brief_title>Validation of USPIO-enhanced MRI for Detection of Lymph Node Metastases in Head and Neck Carcinoma</brief_title>
  <acronym>USPIO-NECK</acronym>
  <official_title>Validation of USPIO-enhanced MRI for Detection of Lymph Node Metastases in Head and Neck Carcinoma: A Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Radboud University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Radboud University Medical Center</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluates the diagnostic accuracy of USPIO enhanced MRI for the detection of lymph&#xD;
      node metastases in head-and-neck squamous cell carcinoma (SCC) using histopathology as a gold&#xD;
      standard.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The presence of lymph node metastases has a large impact on prognosis and treatment in&#xD;
      head-and neck cancer patients and necessitates treatment intensification. Determining lymph&#xD;
      node status, however, is a challenge because up to 20% of patients with a pre-operative&#xD;
      clinically negative neck will have occult metastases in the neck dissection specimen. One&#xD;
      promising technique is USPIO-enhanced MRI, an MR-imaging technique in which ultrasmall&#xD;
      superparamagnetic iron oxide (USPIO) particles are intravenously infused as a contrast agent&#xD;
      in patients 24-36 hours before the MRI examination and has proven to be of value in detecting&#xD;
      lymph node metastases in various types of cancer. The investigators want to validate this&#xD;
      technique in a cohort of head and neck cancer patients who undergo neck dissection surgery.&#xD;
      Histopathology wills serve as the gold standard and the correlation will be made on a&#xD;
      (neck)level-to-level and node-to-node basis. Since the investigators have no experience in&#xD;
      reading USPIO-enhanced MR images of the neck with 3-dimensional iron-sensitive MR sequences,&#xD;
      this study starts with an explorative part and will be followed by the pilot study. The&#xD;
      explorative component aims at obtaining knowledge regarding visual features of&#xD;
      (non-)metastatic cervical lymph nodes on USPIO-enhanced MR images. The purpose is that the&#xD;
      observers work through a learning curve. The information obtained will be used to develop a&#xD;
      scoring system for the radiologic assessment of cervical lymph nodes in the subsequent part&#xD;
      of our study.&#xD;
&#xD;
      If USPIO-enhanced MRI is successful, this may obviate the need for a sentinel node procedure&#xD;
      for example. Furthermore, it could guide treatment such as the performance of more selective&#xD;
      neck dissections and de-escalation of the radiation dose to healthy tissues in order to&#xD;
      decrease morbidity but maintaining high cure rates.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 20, 2019</start_date>
  <completion_date type="Anticipated">April 2023</completion_date>
  <primary_completion_date type="Actual">June 1, 2022</primary_completion_date>
  <phase>N/A</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>Diagnostic accuracy of USPIO-enhanced MRI for detecting lymph node metastases on a level basis.</measure>
    <time_frame>The data of each patient will be assessed prior to neck dissection surgery.</time_frame>
    <description>The images of the USPIO-enhanced MRI will be read by two radiologists who will score each level as cancer (metastases) positive or negative. These results will be compared with the results of pathology which serve as the gold standard to determine the sensitivity, specificity, positive predictive value and negative predictive value of the USPIO-enhanced MRI for detecting lymph node metastases in head-and-neck cancer patients.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Diagnostic accuracy of USPIO-enhanced MRI for detecting lymph node metastases on a nodal basis.</measure>
    <time_frame>The data of each patient will be assessed prior to neck dissection surgery.</time_frame>
    <description>The images of the USPIO-enhanced MRI will be read by two radiologists who will score each node as cancer (metastases) positive or negative. These results will be compared with the results of pathology which serve as the gold standard to determine the sensitivity, specificity, positive predictive value and negative predictive value of the USPIO-enhanced MRI for detecting lymph node metastases in head-and-neck cancer patients.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">25</enrollment>
  <condition>Head and Neck Squamous Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>USPIO enhanced-MRI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The contrast agent ferumoxtran-10 will be administered intravenously under constant medical supervision 24-36 hours before performing a T2* weighted MRI scan (prior to surgery).</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>USPIO-enhanced MRI</intervention_name>
    <description>The USPIO contrast agent will be administered intravenously to the subjects. An MRI scan of the neck region is performed 24-36 hours later to detect lymph node metastases.</description>
    <arm_group_label>USPIO enhanced-MRI</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with histopathologically proven cT0-4N0-3M0 SCC of the oral cavity,&#xD;
             oropharynx, hypopharynx, larynx or unknown primary.&#xD;
&#xD;
          -  Patients planned to undergo a neck dissection.&#xD;
&#xD;
          -  Patient provided written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who underwent radio- and/or chemotherapy to the neck before surgery.&#xD;
&#xD;
          -  Patients who had a previous lymphadenectomy in the head and neck region.&#xD;
&#xD;
          -  Patients with contraindications to MRI (epilepsy; claustrophobia; metallic splinters;&#xD;
             pacemaker, pacemaker wires or implanted defibrillator; implanted magnets in jaw;&#xD;
             arterial clips (carotid arteries); pregnancy; auditory implant, neurogenic bladder&#xD;
             stimulator, insulin pump, neurostimulator, baclofen pump; metallic tissue expander&#xD;
             after mastectomy; cochlear implant; metallic braces; other foreign bodies implanted)&#xD;
&#xD;
          -  Patients with contraindications to USPIO based contrast agents (prior allergic&#xD;
             reaction to ferumoxtran-10 or any other iron preparation; prior allergic reaction&#xD;
             attributed to dextran or other polysaccharide, in any preparation; hereditary&#xD;
             hemochromatosis, hemosiderosis, chronic hemolytic anaemia (e.g. thalassemia, sickle&#xD;
             cell anaemia); pregnancy)&#xD;
&#xD;
          -  Unable to provide informed consent.&#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>Tim Dijkema, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Radboud University Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Hans Kaanders, Prof, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Radboud University Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Daphne Driessen, MD</last_name>
    <phone>+31950008371</phone>
    <email>daphne.driessen@radboudumc.nl</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Tim Dijkema, MD, PhD</last_name>
    <phone>+31243614515</phone>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Radboudumc</name>
      <address>
        <city>Nijmegen</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Daphne Driessen, MD</last_name>
      <email>daphne.driessen@radboudumc.nl</email>
    </contact>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>December 20, 2018</study_first_submitted>
  <study_first_submitted_qc>January 24, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 25, 2019</study_first_posted>
  <last_update_submitted>October 25, 2022</last_update_submitted>
  <last_update_submitted_qc>October 25, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 26, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
    <mesh_term>Lymphatic Metastasis</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/NCT03817307
org study id: USPIO-NECK
nct id: NCT03817307
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This study evaluates the diagnostic accuracy of USPIO enhanced MRI for the detection of lymph
      node metastases in head-and-neck squamous cell carcinoma (SCC) using histopathology as a gold
      standard.
The presence of lymph node metastases has a large impact on prognosis and treatment in
      head-and neck cancer patients and necessitates treatment intensification. Determining lymph
      node status, however, is a challenge because up to 20% of patients with a pre-operative
      clinically negative neck will have occult metastases in the neck dissection specimen. One
      promising technique is USPIO-enhanced MRI, an MR-imaging technique in which ultrasmall
      superparamagnetic iron oxide (USPIO) particles are intravenously infused as a contrast agent
      in patients 24-36 hours before the MRI examination and has proven to be of value in detecting
      lymph node metastases in various types of cancer. The investigators want to validate this
      technique in a cohort of head and neck cancer patients who undergo neck dissection surgery.
      Histopathology wills serve as the gold standard and the correlation will be made on a
      (neck)level-to-level and node-to-node basis. Since the investigators have no experience in
      reading USPIO-enhanced MR images of the neck with 3-dimensional iron-sensitive MR sequences,
      this study starts with an explorative part and will be followed by the pilot study. The
      explorative component aims at obtaining knowledge regarding visual features of
      (non-)metastatic cervical lymph nodes on USPIO-enhanced MR images. The purpose is that the
      observers work through a learning curve. The information obtained will be used to develop a
      scoring system for the radiologic assessment of cervical lymph nodes in the subsequent part
      of our study.

      If USPIO-enhanced MRI is successful, this may obviate the need for a sentinel node procedure
      for example. Furthermore, it could guide treatment such as the performance of more selective
      neck dissections and de-escalation of the radiation dose to healthy tissues in order to
      decrease morbidity but maintaining high cure rates.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Diagnostic accuracy of USPIO-enhanced MRI for detecting lymph node metastases on a level basis.
time frame: The data of each patient will be assessed prior to neck dissection surgery.
description: The images of the USPIO-enhanced MRI will be read by two radiologists who will score each level as cancer (metastases) positive or negative. These results will be compared with the results of pathology which serve as the gold standard to determine the sensitivity, specificity, positive predictive value and negative predictive value of the USPIO-enhanced MRI for detecting lymph node metastases in head-and-neck cancer patients.
measure: Diagnostic accuracy of USPIO-enhanced MRI for detecting lymph node metastases on a nodal basis.
time frame: The data of each patient will be assessed prior to neck dissection surgery.
description: The images of the USPIO-enhanced MRI will be read by two radiologists who will score each node as cancer (metastases) positive or negative. These results will be compared with the results of pathology which serve as the gold standard to determine the sensitivity, specificity, positive predictive value and negative predictive value of the USPIO-enhanced MRI for detecting lymph node metastases in head-and-neck cancer patients.
arm group label: USPIO enhanced-MRI
arm group type: Experimental
description: The contrast agent ferumoxtran-10 will be administered intravenously under constant medical supervision 24-36 hours before performing a T2* weighted MRI scan (prior to surgery).
intervention type: Diagnostic Test
intervention name: USPIO-enhanced MRI
description: The USPIO contrast agent will be administered intravenously to the subjects. An MRI scan of the neck region is performed 24-36 hours later to detect lymph node metastases.
arm group label: USPIO enhanced-MRI
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Tim Dijkema, MD, PhD
role: Principal Investigator
affiliation: Radboud University Medical Center
last name: Hans Kaanders, Prof, MD
role: Principal Investigator
affiliation: Radboud University Medical Center
last name: Daphne Driessen, MD
phone: +31950008371
email: daphne.driessen@radboudumc.nl
last name: Tim Dijkema, MD, PhD
phone: +31243614515
facility: 
status: Recruiting
contact: 
country: Netherlands
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Squamous Cell Carcinoma of Head and Neck
mesh term: Lymphatic Metastasis