<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/NCT01663090</url>
  </required_header>
  <id_info>
    <org_study_id>11-254</org_study_id>
    <nct_id>NCT01663090</nct_id>
  </id_info>
  <brief_title>Ferumoxytol-Enhanced MRI in Adult/Pedi Sarcomas</brief_title>
  <official_title>Ferumoxytol-Enhanced Magnetic Resonance Imaging (MRI) in Pediatric and Adult Patients With Malignant Sarcoma: A Two-part Pilot Study for Safety and Efficacy in the Pediatric and Adult Populations</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dana-Farber Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Dana-Farber Cancer Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This research study is a pilot study to evaluate a new contrast agent, ferumoxytol, for the&#xD;
      purpose of imaging lymph node metastases in patients with soft tissue sarcoma. This contrast&#xD;
      agent is an investigational drug. &quot;Investigational&quot; means that the drug is still being&#xD;
      studied and that research doctors are trying to find out more about it. It also means that&#xD;
      the FDA has not approved ferumoxytol for this use. This drug has been used to image adults&#xD;
      with other forms of cancer, however, it has only been used to image a small number of&#xD;
      pediatric patients. Ferumoxytol has never been used to image sarcoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Before the research starts you will undergo some screening procedures to confirm that you are&#xD;
      eligible to participate in the study. These include a medical history, blood tests and an&#xD;
      electrocardiogram.&#xD;
&#xD;
      After we confirm taht you are eligible for this study you will undergo the following. We&#xD;
      estimate that you will be on the study for approximately two to three weeks.&#xD;
&#xD;
      Baseline MRI of the tumor site and draining lymph nodes: Whether you are on the study or not&#xD;
      you will have a baseline MRI which involves the use of a standard contrast agent called&#xD;
      gadolinium. This imaging test is considered the standard of care and is the method by which&#xD;
      doctors determine tumor location and spread. This MRI is NOT part of the study.&#xD;
&#xD;
      Ferumoxytol Infusion: You will receive this study drug the same day as your baseline MRI; if&#xD;
      you already had your baseline MRI, this medication can be given intravenously (i.e. directly&#xD;
      into the vein) at your next clinical visit. It can likewise be given through a central line.&#xD;
      You will be observed during the infusion and 30 minutes after the infusion to ensure that you&#xD;
      do not have an allergic or adverse reaction to the medication.&#xD;
&#xD;
      Repeat MRI of the tumor site and draining lymph nodes: Three to five days after receiving&#xD;
      ferumoxytol, you will undergo a repeat MRI. You will not require any additional contrast&#xD;
      prior to this imaging study. This MRI is part of the study.&#xD;
&#xD;
      Lymph Node Biopsy: You will be undergoing a lymph node biopsy whether or not you are on the&#xD;
      study. This will occur approximately a week after your study MRI. This is a surgical&#xD;
      procedure that involves removing one or a few lymph nodes in the region of your tumor and&#xD;
      studying them under a microscope to determine whether they contain signs of microscopic&#xD;
      cancer spread. Your surgeon will explain this procedure to you in more detail.&#xD;
&#xD;
      We anticipate that your clinic visit for ferumoxytol will take approximately an hour. MRI&#xD;
      tests, on average, likewise take approximately an hour to complete.&#xD;
&#xD;
      After you have completed the study MRI and lymph node biopsy, you will require one additional&#xD;
      blood test to measure blood iron levels. We measure iron levels because ferumoxytol is&#xD;
      comprised of an iron core. This iron is similar to that in oral iron supplements and can&#xD;
      cause your blood iron levels to temporarily increase. Because we are trying to determine&#xD;
      whether this contrast agent will be useful, you will not receive teh results to the study&#xD;
      MRI. If however, lymph nodes are found to be positive for disease, your treatment plan may&#xD;
      change to address this.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Inability to accrue.&#xD;
  </why_stopped>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">November 2016</completion_date>
  <primary_completion_date type="Actual">November 2016</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>Feasibility and sensitivity of nanoparticle-enhanced MRI</measure>
    <time_frame>4 years</time_frame>
    <description>To determine the feasibility and evaluate the sensitivity of using nanoparticle-enhanced MRI in detecting lymph node metastases in pediatric and adult soft tissue sarcoma patients with clinically palpable or radiographically concerning lymph nodes, whereby the minimum acceptable sensitivity was selected based on a histologic gold standard</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Sensitivity of nanoparticle-enhanced MRI in occult lymph node metastases</measure>
    <time_frame>4 years</time_frame>
    <description>To evaluate the sensitivity of nanoparticle-enhanced MRI in detecting occult lymph node metastases in pediatric and adult patients with soft tissue sarcoma, whereby the minimum acceptable sensitivity was selected based on a histologic gold standard</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety of ferumoxytol in pediatric patients</measure>
    <time_frame>4 years</time_frame>
    <description>The safety of ferumoxytol in pediatric patients will be assessed by the proportion of patients who experience at least one dose limiting toxicity (DLT). DLT refers to toxicities experienced after the start of the drug infusion; they are based on the Common Terminology Criteria for Adverse Events version 4.0.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sensitivity of conventional MRI vs. nanoparticle enhanced MRI</measure>
    <time_frame>4 years</time_frame>
    <description>To evaluate the sensitivity of conventional MRI in detecting the presence of lymph node abnormalities in pediatric and adult patients with soft tissue sarcoma, and to compare this to the sensitivity of nanoparticle-enhanced MRI. The sensitivity of nanoparticle-enhanced MRI will be descriptively compared to the sensitivity of conventional MRI, where in each case the histological confirmation of lymph node involvement is the &quot;standard of truth.&quot; For conventional MRI, sensitivity will be measured by the number of patients in whom at least one lymph node abnormality was detected by conventional MRI, as determined by the primary radiologist, divided by the total number of evaluable patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare inter-reader variability in the interpretation of nanoparticle MRI scans</measure>
    <time_frame>4 years</time_frame>
    <description>To determine inter-reader variability in the interpretation of nanoparticle MRI scans by two independent radiologists. The comparison will be made between each central review radiologist's assessment of whether or not a given patient has a positive lymph node.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Retrospective central pathology review</measure>
    <time_frame>4 years</time_frame>
    <description>To perform a retrospective central pathology review to determine inter-pathologist interpretation of positive lymph nodes. This too will be done through comparison of each central review pathologist's assessment of whether or not a given patient has a positive lymph node.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Soft Tissue Sarcoma</condition>
  <arm_group>
    <arm_group_label>Nanoparticle enhanced MRI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ferumoxytol</intervention_name>
    <arm_group_label>Nanoparticle enhanced MRI</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  New diagnosis of soft tissue sarcoma, who will undergo lymph node biopsy&#xD;
&#xD;
          -  Able to tolerate MRI scan without sedation/anesthesia&#xD;
&#xD;
          -  Greater than or equal to 12 years of age&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous therapy other than biopsy or surgical resection of the primary tumor&#xD;
&#xD;
          -  Pregnant or breastfeeding&#xD;
&#xD;
          -  Receipt of other iron-oxide based nanoparticle therapy within 4 weeks of scans&#xD;
&#xD;
          -  History of allergic reaction to compounds of similar composition to ferumoxytol&#xD;
&#xD;
          -  Known diagnosis of hemochromatosis, mitochondrial disorder or iron overload&#xD;
&#xD;
          -  Invasive bacterial infection&#xD;
&#xD;
          -  Known history of contrast sensitivity&#xD;
&#xD;
          -  Braces or metal heart valve that may interfere with MRI, surgical clips, a pacemaker,&#xD;
             piercings that cannot be removed, or any other indwelling metal device that might&#xD;
             interfere with MRI&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Allison O'Neill, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dana-Farber Cancer Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital Boston</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>July 28, 2012</study_first_submitted>
  <study_first_submitted_qc>August 8, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2012</study_first_posted>
  <last_update_submitted>October 14, 2020</last_update_submitted>
  <last_update_submitted_qc>October 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 19, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Dana-Farber Cancer Institute</investigator_affiliation>
    <investigator_full_name>Allison O'Neill</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Newly diagnosed</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sarcoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ferrosoferric Oxide</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/NCT01663090
org study id: 11-254
nct id: NCT01663090
lead sponsor: 
has dmc: Yes
This research study is a pilot study to evaluate a new contrast agent, ferumoxytol, for the
      purpose of imaging lymph node metastases in patients with soft tissue sarcoma. This contrast
      agent is an investigational drug. "Investigational" means that the drug is still being
      studied and that research doctors are trying to find out more about it. It also means that
      the FDA has not approved ferumoxytol for this use. This drug has been used to image adults
      with other forms of cancer, however, it has only been used to image a small number of
      pediatric patients. Ferumoxytol has never been used to image sarcoma.
Before the research starts you will undergo some screening procedures to confirm that you are
      eligible to participate in the study. These include a medical history, blood tests and an
      electrocardiogram.

      After we confirm taht you are eligible for this study you will undergo the following. We
      estimate that you will be on the study for approximately two to three weeks.

      Baseline MRI of the tumor site and draining lymph nodes: Whether you are on the study or not
      you will have a baseline MRI which involves the use of a standard contrast agent called
      gadolinium. This imaging test is considered the standard of care and is the method by which
      doctors determine tumor location and spread. This MRI is NOT part of the study.

      Ferumoxytol Infusion: You will receive this study drug the same day as your baseline MRI; if
      you already had your baseline MRI, this medication can be given intravenously (i.e. directly
      into the vein) at your next clinical visit. It can likewise be given through a central line.
      You will be observed during the infusion and 30 minutes after the infusion to ensure that you
      do not have an allergic or adverse reaction to the medication.

      Repeat MRI of the tumor site and draining lymph nodes: Three to five days after receiving
      ferumoxytol, you will undergo a repeat MRI. You will not require any additional contrast
      prior to this imaging study. This MRI is part of the study.

      Lymph Node Biopsy: You will be undergoing a lymph node biopsy whether or not you are on the
      study. This will occur approximately a week after your study MRI. This is a surgical
      procedure that involves removing one or a few lymph nodes in the region of your tumor and
      studying them under a microscope to determine whether they contain signs of microscopic
      cancer spread. Your surgeon will explain this procedure to you in more detail.

      We anticipate that your clinic visit for ferumoxytol will take approximately an hour. MRI
      tests, on average, likewise take approximately an hour to complete.

      After you have completed the study MRI and lymph node biopsy, you will require one additional
      blood test to measure blood iron levels. We measure iron levels because ferumoxytol is
      comprised of an iron core. This iron is similar to that in oral iron supplements and can
      cause your blood iron levels to temporarily increase. Because we are trying to determine
      whether this contrast agent will be useful, you will not receive teh results to the study
      MRI. If however, lymph nodes are found to be positive for disease, your treatment plan may
      change to address this.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Feasibility and sensitivity of nanoparticle-enhanced MRI
time frame: 4 years
description: To determine the feasibility and evaluate the sensitivity of using nanoparticle-enhanced MRI in detecting lymph node metastases in pediatric and adult soft tissue sarcoma patients with clinically palpable or radiographically concerning lymph nodes, whereby the minimum acceptable sensitivity was selected based on a histologic gold standard
measure: Sensitivity of nanoparticle-enhanced MRI in occult lymph node metastases
time frame: 4 years
description: To evaluate the sensitivity of nanoparticle-enhanced MRI in detecting occult lymph node metastases in pediatric and adult patients with soft tissue sarcoma, whereby the minimum acceptable sensitivity was selected based on a histologic gold standard
measure: Safety of ferumoxytol in pediatric patients
time frame: 4 years
description: The safety of ferumoxytol in pediatric patients will be assessed by the proportion of patients who experience at least one dose limiting toxicity (DLT). DLT refers to toxicities experienced after the start of the drug infusion; they are based on the Common Terminology Criteria for Adverse Events version 4.0.
measure: Sensitivity of conventional MRI vs. nanoparticle enhanced MRI
time frame: 4 years
description: To evaluate the sensitivity of conventional MRI in detecting the presence of lymph node abnormalities in pediatric and adult patients with soft tissue sarcoma, and to compare this to the sensitivity of nanoparticle-enhanced MRI. The sensitivity of nanoparticle-enhanced MRI will be descriptively compared to the sensitivity of conventional MRI, where in each case the histological confirmation of lymph node involvement is the "standard of truth." For conventional MRI, sensitivity will be measured by the number of patients in whom at least one lymph node abnormality was detected by conventional MRI, as determined by the primary radiologist, divided by the total number of evaluable patients.
measure: Compare inter-reader variability in the interpretation of nanoparticle MRI scans
time frame: 4 years
description: To determine inter-reader variability in the interpretation of nanoparticle MRI scans by two independent radiologists. The comparison will be made between each central review radiologist's assessment of whether or not a given patient has a positive lymph node.
measure: Retrospective central pathology review
time frame: 4 years
description: To perform a retrospective central pathology review to determine inter-pathologist interpretation of positive lymph nodes. This too will be done through comparison of each central review pathologist's assessment of whether or not a given patient has a positive lymph node.
arm group label: Nanoparticle enhanced MRI
arm group type: Experimental
intervention type: Drug
intervention name: Ferumoxytol
arm group label: Nanoparticle enhanced MRI
criteria: 
gender: All
minimum age: 12 Years
maximum age: N/A
healthy volunteers: No
last name: Allison O'Neill, MD
role: Principal Investigator
affiliation: Dana-Farber Cancer Institute
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Dana-Farber Cancer Institute
investigator full name: Allison O'Neill
investigator title: Principal Investigator
mesh term: Sarcoma
mesh term: Ferrosoferric Oxide