xml: <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/NCT05985551</url>
    </required_header>
    <id_info>
      <org_study_id>UUBreast03</org_study_id>
      <nct_id>NCT05985551</nct_id>
    </id_info>
    <brief_title>Delayed SLND for Patients With Breast Cancer Undergoing Primary Systemic Treatment</brief_title>
    <acronym>MagNeo</acronym>
    <official_title>A Feasibility Study on the Timeframe of Superparamagnetic Iron Oxide Nanoparticles Administration in Patients Receiving Primary Systemic Therapy for Early Breast Cancer</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Uppsala University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Uppsala University Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Uppsala University</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
    </oversight_info>
    <brief_summary>
      <textblock>
        The goal of this study was to assess the feasibility of SLND by superparamagnetic iron oxide&#xD;
        nanoparticles (SPIO) in patients with early breast cancer planned for primary systemic&#xD;
        therapy (PST) and whether this is affected by the timeframe of SPIO administration.&#xD;
  &#xD;
        For this, patients with cN0/1 disease planned for PST received radioisotope as per routine on&#xD;
        the day of surgery or the day before, and SPIO was injected in an extended timeframe, at any&#xD;
        point from the day of surgery to before the induction of PST.&#xD;
  &#xD;
        The main points to investigate are:&#xD;
  &#xD;
          1. If the SPIO detection rate and concordance to the radiosotope are affected by time of&#xD;
             SPIO injection&#xD;
  &#xD;
          2. If the nodal yield and the accuracy of the procedure are affected&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Superparamagnetic Iron Nanoparticles (SPIO) have shown comparable performance to the standard&#xD;
        of Radioisotope (RI) +/- blue dye (BD) for Sentinel Lymph Node Detection in breast cancer,&#xD;
        with the advantage of clinical convenience due to easier accessibility, disposal and&#xD;
        injection days before surgery.&#xD;
  &#xD;
        More interestingly, SPIO provides the possibility for delayed SLND in the setting of a&#xD;
        preoperative diagnosis of DCIS, enabling SLN detection weeks after breast surgery, only when&#xD;
        specimen pathology has demonstrated invasive cancer, as shown in the SentiNot study. The role&#xD;
        of SPIO for SLND in the setting of primary systemic therapy (PST) has not been extensively&#xD;
        investigated, while the timeframe from SPIO administration to successful SLN detection in a&#xD;
        similar fashion to SentiNot, but in the setting of PST has yet to been defined.&#xD;
  &#xD;
        Current evidence suggest that RI-based SLN detection is the accepted standard following PST,&#xD;
        with RI-based dual mapping specifically recommended in cN+-to-ycN0 patients, when SLND or&#xD;
        targeted axillary dissection (TAD) are performed, as the number of SLNs retrieved has been&#xD;
        inversely linked to the false negative rate of the procedure.&#xD;
  &#xD;
        Apart from the logistic benefits of SPIO administration prior to PST, an aspect of potential&#xD;
        interest is the ability to map the axilla, before the fibrotic changes induced by&#xD;
        chemotherapy and lymphatic remodelling occur, that are a concern, especially in the&#xD;
        node-positive patients at presentation.&#xD;
  &#xD;
        However, in this case, it is imperative to investigate that SPIO remains detectable after a&#xD;
        prolonged period of administration and that it does not migrate to higher nodal echelons.&#xD;
        While preliminary data suggested feasibility, the aim of this dedicated study was to&#xD;
        investigate the width of timeframe of SPIO administration in patients undergoing PST and how&#xD;
        SPIO-based detection and concordance to the RI are affected.&#xD;
  &#xD;
        In this study, patients scheduled for SLND or TAD after surgery will undergo the procedure&#xD;
        with RI as the standard of care and will moreover receive SPIO. The administration of SPIO&#xD;
        will take place either on the preoperative period but after the completion of PST, or before&#xD;
        the induction of PST. The reason for this is to create a wide time-frame to allow for&#xD;
        conclusion with regards to whether the mapping of the axilla prior PST by SPIO is a feasible&#xD;
        technique that will then be addressed in a dedicated trial.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Active, not recruiting</overall_status>
    <start_date type="Actual">January 1, 2020</start_date>
    <completion_date type="Anticipated">October 30, 2023</completion_date>
    <primary_completion_date type="Actual">October 30, 2022</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Other</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Correlation between concordance (isotope and SPIO) and timepoint of SPIO administration to surgery</measure>
      <time_frame>At surgery</time_frame>
      <description>This endpoint is necessary in ensuring that prolonged SPIO administration does not result in the retrieval of &quot;false&quot; SLNs, in the case that SPIO migrates to higher nodal echelons. As the radioisotope is the current standard of care, the concordance of SPIO to the radioisotope and its correlation with time of SPIO adminstration is the appropriate surrogate endpoint.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Detection rate</measure>
      <time_frame>At surgery</time_frame>
      <description>The successful retrieval of at least one SLN detected by each tracer (SPIO or radioisotope) separately.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Concordance</measure>
      <time_frame>At surgery</time_frame>
      <description>The rate (patients with at least one SLN detected with both tracers/patients with at least one SLN detected with the radioisotope)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Nodal yield</measure>
      <time_frame>At surgery</time_frame>
      <description>The median number of SLNs retrieved with each tracer</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Nodal concordance</measure>
      <time_frame>At surgery</time_frame>
      <description>The rate (SLNs detected by both tracers/SLNs detected by the radioisotope)</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Detection rate for 2 and 3 SLNs</measure>
      <time_frame>At surgery</time_frame>
      <description>The successful retrieval of at least two and at least three SLN detected by each tracer (SPIO or radioisotope) separately.</description>
    </other_outcome>
    <other_outcome>
      <measure>Adverse events</measure>
      <time_frame>From time of SPIO administration to four weeks after surgery</time_frame>
      <description>Any adverse events reported in relation to SPIO administration</description>
    </other_outcome>
    <enrollment type="Anticipated">114</enrollment>
    <condition>Breast Cancer</condition>
    <condition>Chemotherapy Effect</condition>
    <condition>Sentinel Lymph Node</condition>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>SLND or TAD by the magnetic technique (SPIO)</intervention_name>
      <description>All patients will receive Radioisotope according to standard of care. They will also receive SPIO in a timeframe of clinical convenience, depending on whether primary response is planned by means of MRI. For patients that are ycN0, SLND or TAD will be performed. For those that convert from cN1 to ycN0, the index lymph node will be marked with a paramagnetic marker. Axillary surgery will be undertaken with the magnetic technique and each retrieved lymph node will be controlled for radiation. Upon the completion of the procedure, a background control will be performed with the radioactive signal as guide, to ensure standard of care best practice. Any palpable lymph nodes that are not sentinels with either tracer may be removed at surgeon discretion but will be reported seperately.</description>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          Patients that fulfilled all eligibility criteria as listed above&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Adult patients with non-metastatic primary breast cancer and cN0/cN1 axilla, as&#xD;
               defined by clinical examination and axillary ultrasound (with fine needle aspiration&#xD;
               or core biopsy verification of metastasis) intended for PST (chemotherapy, targeted&#xD;
               treatment or endocrine therapy) with a curative intention at diagnosis,&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Distant metastases at diagnosis&#xD;
  &#xD;
            -  Inflammatory breast cancer&#xD;
  &#xD;
            -  Tumor progression during PST for cN1 patients&#xD;
  &#xD;
            -  ycN1 after completion of PST&#xD;
  &#xD;
            -  surgery before the completion of PST for any reason (PST adverse effects, patient&#xD;
               preference)&#xD;
  &#xD;
            -  cN1-to-ycN0 patients that opted for ALND&#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>Andreas U Karakatsanis, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Uppsala University</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>Uppsala University Hospital</name>
        <address>
          <city>Uppsala</city>
          <zip>75185</zip>
          <country>Sweden</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Sweden</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 2, 2023</study_first_submitted>
    <study_first_submitted_qc>August 2, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 2, 2023</last_update_submitted>
    <last_update_submitted_qc>August 2, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Uppsala University</investigator_affiliation>
      <investigator_full_name>Andreas Karakatsanis</investigator_full_name>
      <investigator_title>Associate Professor, MD, PhD</investigator_title>
    </responsible_party>
    <keyword>Neoadjuvant therapy</keyword>
    <keyword>Breast Cancer</keyword>
    <keyword>Superparamagnetic Iron oxide nanoparticles</keyword>
    <keyword>SLND</keyword>
    <keyword>Targeted axillary Dissection</keyword>
    <keyword>Delayed SLND</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Breast Neoplasms</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>Patients have not been consented for IPD and separate consent should be sought for this. For any interest, contact andreas.karakatsanis@uu.se</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05985551
  org study id: UUBreast03
  nct id: NCT05985551
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  The goal of this study was to assess the feasibility of SLND by superparamagnetic iron oxide
        nanoparticles (SPIO) in patients with early breast cancer planned for primary systemic
        therapy (PST) and whether this is affected by the timeframe of SPIO administration.
  
        For this, patients with cN0/1 disease planned for PST received radioisotope as per routine on
        the day of surgery or the day before, and SPIO was injected in an extended timeframe, at any
        point from the day of surgery to before the induction of PST.
  
        The main points to investigate are:
  
          1. If the SPIO detection rate and concordance to the radiosotope are affected by time of
             SPIO injection
  
          2. If the nodal yield and the accuracy of the procedure are affected
  Superparamagnetic Iron Nanoparticles (SPIO) have shown comparable performance to the standard
        of Radioisotope (RI) +/- blue dye (BD) for Sentinel Lymph Node Detection in breast cancer,
        with the advantage of clinical convenience due to easier accessibility, disposal and
        injection days before surgery.
  
        More interestingly, SPIO provides the possibility for delayed SLND in the setting of a
        preoperative diagnosis of DCIS, enabling SLN detection weeks after breast surgery, only when
        specimen pathology has demonstrated invasive cancer, as shown in the SentiNot study. The role
        of SPIO for SLND in the setting of primary systemic therapy (PST) has not been extensively
        investigated, while the timeframe from SPIO administration to successful SLN detection in a
        similar fashion to SentiNot, but in the setting of PST has yet to been defined.
  
        Current evidence suggest that RI-based SLN detection is the accepted standard following PST,
        with RI-based dual mapping specifically recommended in cN+-to-ycN0 patients, when SLND or
        targeted axillary dissection (TAD) are performed, as the number of SLNs retrieved has been
        inversely linked to the false negative rate of the procedure.
  
        Apart from the logistic benefits of SPIO administration prior to PST, an aspect of potential
        interest is the ability to map the axilla, before the fibrotic changes induced by
        chemotherapy and lymphatic remodelling occur, that are a concern, especially in the
        node-positive patients at presentation.
  
        However, in this case, it is imperative to investigate that SPIO remains detectable after a
        prolonged period of administration and that it does not migrate to higher nodal echelons.
        While preliminary data suggested feasibility, the aim of this dedicated study was to
        investigate the width of timeframe of SPIO administration in patients undergoing PST and how
        SPIO-based detection and concordance to the RI are affected.
  
        In this study, patients scheduled for SLND or TAD after surgery will undergo the procedure
        with RI as the standard of care and will moreover receive SPIO. The administration of SPIO
        will take place either on the preoperative period but after the completion of PST, or before
        the induction of PST. The reason for this is to create a wide time-frame to allow for
        conclusion with regards to whether the mapping of the axilla prior PST by SPIO is a feasible
        technique that will then be addressed in a dedicated trial.
  observational model: Other
  time perspective: Prospective
  measure: Correlation between concordance (isotope and SPIO) and timepoint of SPIO administration to surgery
  time frame: At surgery
  description: This endpoint is necessary in ensuring that prolonged SPIO administration does not result in the retrieval of "false" SLNs, in the case that SPIO migrates to higher nodal echelons. As the radioisotope is the current standard of care, the concordance of SPIO to the radioisotope and its correlation with time of SPIO adminstration is the appropriate surrogate endpoint.
  measure: Detection rate
  time frame: At surgery
  description: The successful retrieval of at least one SLN detected by each tracer (SPIO or radioisotope) separately.
  measure: Concordance
  time frame: At surgery
  description: The rate (patients with at least one SLN detected with both tracers/patients with at least one SLN detected with the radioisotope)
  measure: Nodal yield
  time frame: At surgery
  description: The median number of SLNs retrieved with each tracer
  measure: Nodal concordance
  time frame: At surgery
  description: The rate (SLNs detected by both tracers/SLNs detected by the radioisotope)
  measure: Detection rate for 2 and 3 SLNs
  time frame: At surgery
  description: The successful retrieval of at least two and at least three SLN detected by each tracer (SPIO or radioisotope) separately.
  measure: Adverse events
  time frame: From time of SPIO administration to four weeks after surgery
  description: Any adverse events reported in relation to SPIO administration
  intervention type: Other
  intervention name: SLND or TAD by the magnetic technique (SPIO)
  description: All patients will receive Radioisotope according to standard of care. They will also receive SPIO in a timeframe of clinical convenience, depending on whether primary response is planned by means of MRI. For patients that are ycN0, SLND or TAD will be performed. For those that convert from cN1 to ycN0, the index lymph node will be marked with a paramagnetic marker. Axillary surgery will be undertaken with the magnetic technique and each retrieved lymph node will be controlled for radiation. Upon the completion of the procedure, a background control will be performed with the radioactive signal as guide, to ensure standard of care best practice. Any palpable lymph nodes that are not sentinels with either tracer may be removed at surgeon discretion but will be reported seperately.
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Andreas U Karakatsanis, MD, PhD
  role: Principal Investigator
  affiliation: Uppsala University
  facility: 
  country: Sweden
  responsible party type: Principal Investigator
  investigator affiliation: Uppsala University
  investigator full name: Andreas Karakatsanis
  investigator title: Associate Professor, MD, PhD
  mesh term: Breast Neoplasms
  sharing ipd: No
  ipd description: Patients have not been consented for IPD and separate consent should be sought for this. For any interest, contact andreas.karakatsanis@uu.se