<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/NCT03280277</url>
  </required_header>
  <id_info>
    <org_study_id>STUDY00016101</org_study_id>
    <secondary_id>NCI-2017-00388</secondary_id>
    <secondary_id>ONC-16108-L</secondary_id>
    <secondary_id>STUDY00016101</secondary_id>
    <nct_id>NCT03280277</nct_id>
  </id_info>
  <brief_title>Ferumoxytol-Enhanced MRI in Imaging Lymph Nodes in Patients With Locally Advanced Rectal Cancer</brief_title>
  <official_title>Novel Imaging of Lymph Nodes in Patients With Rectal Cancer Using Ferumoxytol Enhanced MRI</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>OHSU Knight Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Oregon Health and Science University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Radiological Society of North America</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>OHSU Knight Cancer Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This pilot clinical trial studies how well ferumoxytol-enhanced magnetic resonance imaging&#xD;
      (MRI) works in imaging lymph nodes in patients with rectal cancer that has spread from where&#xD;
      it started to nearby tissue or lymph nodes (locally advanced). Ferumoxytol is a form of very&#xD;
      small iron particles that are taken up by cells in normal lymph nodes and may work better in&#xD;
      imaging patients with rectal cancer when given with MRI.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To determine feasibility of administering ferumoxytol and obtaining ferumoxytol enhanced&#xD;
      magnetic resonance (MR) images in patients with resectable locally advanced rectal cancer&#xD;
      with enlarged or suspicious lateral pelvic lymph nodes before starting neoadjuvant therapy&#xD;
      and again before total mesorectal excision.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To collect detailed information about the location of ultrasmall superparamagnetic iron&#xD;
      oxide (USPIO)-MRI detected lymph nodes prior to neoadjuvant therapy and again prior to total&#xD;
      mesorectal excision.&#xD;
&#xD;
      II. To compare the sensitivity and specificity of ferumoxytol enhanced MR imaging in&#xD;
      assessment of pathological lymph nodes with those of non-USPIO-MRI and positron emission&#xD;
      tomography-computed tomography (PET-CT).&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive ferumoxytol intravenously (IV) over 15 minutes and then after 24-36 hours&#xD;
      undergo ferumoxytol-enhanced MRI before start of neoadjuvant therapy and within 4 weeks&#xD;
      before surgery.&#xD;
&#xD;
      After completion of study treatment, patients are followed up for 4-6 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    low accrual&#xD;
  </why_stopped>
  <start_date type="Actual">April 27, 2018</start_date>
  <completion_date type="Actual">August 26, 2021</completion_date>
  <primary_completion_date type="Actual">August 26, 2021</primary_completion_date>
  <phase>Early Phase 1</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>Practical feasibility</measure>
    <time_frame>Up to 6 weeks</time_frame>
    <description>Assessed by successful accrual objectively, as a percentage of all subjects enrolled. Accrual success will be measured in binary fashion; successful accrual is considered a patient that enrolls and completes the entire trial. All other eligible patients will be considered an accrual failure. Practical feasibility will be considered a success if greater than 50%.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Technical feasibility of ultrasmall superparamagnetic iron oxide (USPIO) - magnetic resonance imaging (MRI) of the chest</measure>
    <time_frame>Up to 6 weeks</time_frame>
    <description>Assessed by image quality and protocol completion. Will be evaluated in a descriptive manner. Image quality, readability (i.e. the ability for diagnostic radiologist to make an appropriate diagnostic conclusion), completion of ferumoxytol infusion, data acquisition, and completion of magnetic resonance protocol.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Reason for accrual failure</measure>
    <time_frame>Up to 6 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Report location and enhancement patterns on USPIO - MRI</measure>
    <time_frame>Up to 6 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sensitivity and specificity of MRI imaging for all lymph nodes</measure>
    <time_frame>Up to 6 weeks</time_frame>
    <description>Assessed by pathology finding. Sensitivities and specificities of ferumoxytol enhanced MRI prior to neoadjuvant therapy will be calculated using pathology finding as the gold standard. Each lymph node will be treated as an independent observation. The sensitivity and specificity will be compared with those from positron emission tomography (PET)/computed tomography (CT) findings using McNemar's test. Sensitivities and specificities of ferumoxytol enhanced MRI before surgery will also be calculated as a reference.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sensitivity and specificity of PET/CT imaging</measure>
    <time_frame>Up to 6 weeks</time_frame>
    <description>Assessed by pathology finding. Sensitivities and specificities of ferumoxytol enhanced MRI prior to neoadjuvant therapy will be calculated using pathology finding as the gold standard. Each lymph node will be treated as an independent observation. The sensitivity and specificity will be compared with those from PET/CT findings using McNemar's test. Sensitivities and specificities of ferumoxytol enhanced MRI before surgery will also be calculated as a reference.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accuracy of USPIO - MRI</measure>
    <time_frame>Up to 6 weeks</time_frame>
    <description>Accuracy, which is defined as the percentage of all patients or lymph nodes in which MRI with ferumoxytol correctly predicted the presence or absence of metastatic tumor, will be calculated.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">2</enrollment>
  <condition>Locally Advanced Rectal Carcinoma</condition>
  <condition>Stage III Rectal Cancer AJCC v7</condition>
  <condition>Stage IIIA Rectal Cancer AJCC v7</condition>
  <condition>Stage IIIB Rectal Cancer AJCC v7</condition>
  <condition>Stage IIIC Rectal Cancer AJCC v7</condition>
  <arm_group>
    <arm_group_label>Diagnostic (ferumoxytol-enhanced MRI)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive ferumoxytol IV over 15 minutes and then after 24-36 hours undergo ferumoxytol-enhanced MRI before start of neoadjuvant therapy and within 4 weeks before surgery.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Contrast-enhanced Magnetic Resonance Imaging</intervention_name>
    <description>Undergo ferumoxytol-enhanced MRI</description>
    <arm_group_label>Diagnostic (ferumoxytol-enhanced MRI)</arm_group_label>
    <other_name>CONTRAST ENHANCED MRI</other_name>
    <other_name>Contrast-enhanced MRI</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ferumoxytol</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Diagnostic (ferumoxytol-enhanced MRI)</arm_group_label>
    <other_name>Feraheme</other_name>
    <other_name>Ferumoxytol Non-Stoichiometric Magnetite</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pathologically confirmed, locally advanced, malignancy of the rectum; based on&#xD;
             multi-disciplinary tumor board discussion, patients are candidates for tri-modality&#xD;
             treatment&#xD;
&#xD;
          -  Stage T1-4bN1-2, by the American Joint Committee on Cancer (AJCC) 7th edition, based&#xD;
             on the following minimum workup:&#xD;
&#xD;
               -  CT chest/abdomen with contrast&#xD;
&#xD;
               -  MRI pelvis with contrast&#xD;
&#xD;
               -  PET/CT of the whole-body or skull base to mid-thigh&#xD;
&#xD;
          -  Subjects must have had no prior therapy for cancer of the rectum&#xD;
&#xD;
          -  Members of all races and ethnic groups will be included&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status =&lt; 2 (Karnofsky &gt;= 60%)&#xD;
&#xD;
          -  White blood cell count &gt;= 3.0 K/cu mm&#xD;
&#xD;
          -  Absolute neutrophil count &gt;= 1.5 K/cu mm&#xD;
&#xD;
          -  Platelets &gt;= 100 K/cu mm&#xD;
&#xD;
          -  Hemoglobin &gt;= 8.0 g/dl (the use of transfusion or other invention to achieve&#xD;
             hemoglobin [Hgb] &gt;= 8.0 g/dl is acceptable)&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 X institutional upper limit of normal&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase&#xD;
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])&#xD;
             =&lt; 2.5 X institutional upper limit of normal&#xD;
&#xD;
          -  Creatinine within normal institutional limits OR creatinine clearance &gt;= 60&#xD;
             mL/min/1.73 m^2 for subjects with creatinine levels above institutional normal&#xD;
&#xD;
          -  Woman of childbearing potential, a negative serum or urine pregnancy test&#xD;
&#xD;
          -  Willingness to use adequate contraception for 12 months after completion of all&#xD;
             therapy&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with AJCC 7th edition stage TxN0 and/or metastatic disease outside of pelvis&#xD;
             (suspicious lateral pelvic lymph nodes up to and including common iliacs are allowed&#xD;
             on the protocol)&#xD;
&#xD;
          -  Prior systemic chemotherapy for rectal cancer; prior chemotherapy for another&#xD;
             malignancy is allowable as long as it has been &gt; 2 years since completion of therapy&#xD;
             for previous malignancy&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to ferumoxytol or other agents used in the study&#xD;
&#xD;
          -  Prior abdominopelvic radiation or radiation for rectal cancer&#xD;
&#xD;
          -  History of other malignancy in the past 2 years except non-melanomatous skin cancer,&#xD;
             breast ductal carcinoma in situ (DCIS) and low-risk prostate adenocarcinoma&#xD;
&#xD;
          -  Medical contraindications to low anterior resection or abdominoperineal resection&#xD;
&#xD;
          -  Uncontrolled concurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements&#xD;
&#xD;
          -  Pregnant women are excluded from this study because chemoradiotherapy has the&#xD;
             potential for teratogenic or abortifacient effects; because there is an unknown but&#xD;
             potential risk for adverse events in nursing infants secondary to the use of&#xD;
             ferumoxytol as a contrast agent in the mother, breastfeeding should be discontinued if&#xD;
             the mother receives ferumoxytol while nursing; men who are sexually active and not&#xD;
             willing/able to use medically acceptable forms of contraception are also excluded from&#xD;
             this study&#xD;
&#xD;
          -  Subjects with multiple drug allergies and/or subjects who have had an allergic&#xD;
             reaction to any intravenous iron replacement product or a known history of&#xD;
             hypersensitivity to ferumoxytol&#xD;
&#xD;
          -  Subjects with concurrent clinical diagnosis of evidence of active iron overload&#xD;
             defined by the following 1) ferritin &gt;= 250 ng/mL in men or &gt;= 200 ng/mL in women AND&#xD;
             2) transferrin saturation, the ratio of plasma iron to transferrin, expressed as&#xD;
             percent, &gt;= 45%&#xD;
&#xD;
          -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral&#xD;
             therapy are ineligible because of the potential for pharmacokinetic interactions with&#xD;
             ferumoxytol&#xD;
&#xD;
          -  Patients with renal insufficiency; glomerular filtration rate (GFR) &lt; 60&#xD;
&#xD;
          -  Adult patients who require monitored anesthesia for MRI scanning&#xD;
&#xD;
          -  Subjects who have a contraindication for MRI: metal in their bodies (a cardiac&#xD;
             pacemaker or other incompatible device), are severely agitated, or have an allergy to&#xD;
             gadolinium (Gd) contrast material&#xD;
&#xD;
          -  Subjects with known hepatic insufficiency or cirrhosis as determined by either a prior&#xD;
             diagnosing physician or at review at initial consultation; these disease entities do&#xD;
             not have formal associated lab values and are thus a clinical diagnosis by the prior&#xD;
             aforementioned physician&#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>Alexander Guimaraes</last_name>
    <role>Principal Investigator</role>
    <affiliation>OHSU Knight Cancer Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>OHSU Knight Cancer Institute</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>May 23, 2017</study_first_submitted>
  <study_first_submitted_qc>September 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 12, 2017</study_first_posted>
  <last_update_submitted>September 2, 2021</last_update_submitted>
  <last_update_submitted_qc>September 2, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 10, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>OHSU Knight Cancer Institute</investigator_affiliation>
    <investigator_full_name>Alexander Guimaraes</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rectal Neoplasms</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/NCT03280277
org study id: STUDY00016101
secondary id: NCI-2017-00388
secondary id: ONC-16108-L
secondary id: STUDY00016101
nct id: NCT03280277
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This pilot clinical trial studies how well ferumoxytol-enhanced magnetic resonance imaging
      (MRI) works in imaging lymph nodes in patients with rectal cancer that has spread from where
      it started to nearby tissue or lymph nodes (locally advanced). Ferumoxytol is a form of very
      small iron particles that are taken up by cells in normal lymph nodes and may work better in
      imaging patients with rectal cancer when given with MRI.
PRIMARY OBJECTIVE:

      I. To determine feasibility of administering ferumoxytol and obtaining ferumoxytol enhanced
      magnetic resonance (MR) images in patients with resectable locally advanced rectal cancer
      with enlarged or suspicious lateral pelvic lymph nodes before starting neoadjuvant therapy
      and again before total mesorectal excision.

      SECONDARY OBJECTIVES:

      I. To collect detailed information about the location of ultrasmall superparamagnetic iron
      oxide (USPIO)-MRI detected lymph nodes prior to neoadjuvant therapy and again prior to total
      mesorectal excision.

      II. To compare the sensitivity and specificity of ferumoxytol enhanced MR imaging in
      assessment of pathological lymph nodes with those of non-USPIO-MRI and positron emission
      tomography-computed tomography (PET-CT).

      OUTLINE:

      Patients receive ferumoxytol intravenously (IV) over 15 minutes and then after 24-36 hours
      undergo ferumoxytol-enhanced MRI before start of neoadjuvant therapy and within 4 weeks
      before surgery.

      After completion of study treatment, patients are followed up for 4-6 weeks.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Practical feasibility
time frame: Up to 6 weeks
description: Assessed by successful accrual objectively, as a percentage of all subjects enrolled. Accrual success will be measured in binary fashion; successful accrual is considered a patient that enrolls and completes the entire trial. All other eligible patients will be considered an accrual failure. Practical feasibility will be considered a success if greater than 50%.
measure: Technical feasibility of ultrasmall superparamagnetic iron oxide (USPIO) - magnetic resonance imaging (MRI) of the chest
time frame: Up to 6 weeks
description: Assessed by image quality and protocol completion. Will be evaluated in a descriptive manner. Image quality, readability (i.e. the ability for diagnostic radiologist to make an appropriate diagnostic conclusion), completion of ferumoxytol infusion, data acquisition, and completion of magnetic resonance protocol.
measure: Reason for accrual failure
time frame: Up to 6 weeks
measure: Report location and enhancement patterns on USPIO - MRI
time frame: Up to 6 weeks
measure: Sensitivity and specificity of MRI imaging for all lymph nodes
time frame: Up to 6 weeks
description: Assessed by pathology finding. Sensitivities and specificities of ferumoxytol enhanced MRI prior to neoadjuvant therapy will be calculated using pathology finding as the gold standard. Each lymph node will be treated as an independent observation. The sensitivity and specificity will be compared with those from positron emission tomography (PET)/computed tomography (CT) findings using McNemar's test. Sensitivities and specificities of ferumoxytol enhanced MRI before surgery will also be calculated as a reference.
measure: Sensitivity and specificity of PET/CT imaging
time frame: Up to 6 weeks
description: Assessed by pathology finding. Sensitivities and specificities of ferumoxytol enhanced MRI prior to neoadjuvant therapy will be calculated using pathology finding as the gold standard. Each lymph node will be treated as an independent observation. The sensitivity and specificity will be compared with those from PET/CT findings using McNemar's test. Sensitivities and specificities of ferumoxytol enhanced MRI before surgery will also be calculated as a reference.
measure: Accuracy of USPIO - MRI
time frame: Up to 6 weeks
description: Accuracy, which is defined as the percentage of all patients or lymph nodes in which MRI with ferumoxytol correctly predicted the presence or absence of metastatic tumor, will be calculated.
arm group label: Diagnostic (ferumoxytol-enhanced MRI)
arm group type: Experimental
description: Patients receive ferumoxytol IV over 15 minutes and then after 24-36 hours undergo ferumoxytol-enhanced MRI before start of neoadjuvant therapy and within 4 weeks before surgery.
intervention type: Procedure
intervention name: Contrast-enhanced Magnetic Resonance Imaging
description: Undergo ferumoxytol-enhanced MRI
arm group label: Diagnostic (ferumoxytol-enhanced MRI)
other name: CONTRAST ENHANCED MRI
other name: Contrast-enhanced MRI
intervention type: Drug
intervention name: Ferumoxytol
description: Given IV
arm group label: Diagnostic (ferumoxytol-enhanced MRI)
other name: Feraheme
other name: Ferumoxytol Non-Stoichiometric Magnetite
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Alexander Guimaraes
role: Principal Investigator
affiliation: OHSU Knight Cancer Institute
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: OHSU Knight Cancer Institute
investigator full name: Alexander Guimaraes
investigator title: Associate Professor
mesh term: Rectal Neoplasms
mesh term: Ferrosoferric Oxide