<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/NCT02240472</url>
  </required_header>
  <id_info>
    <org_study_id>SENOMAC</org_study_id>
    <nct_id>NCT02240472</nct_id>
  </id_info>
  <brief_title>Sentinel Node Biopsy in Breast Cancer: Omission of Axillary Clearance After Macrometastases. A Randomized Trial.</brief_title>
  <official_title>Survival and Axillary Recurrence Following Sentinel Node-positive Breast Cancer Without Completion Axillary Lymph Node Dissection - a Randomized Study of Patients With Macrometastases in the Sentinel Node</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Karolinska Institutet</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Swedish Research Council</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Swedish Cancer Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Nordic Cancer Union</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Karolinska Institutet</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Since the introduction of sentinel node biopsy in breast cancer, it has become clear that its&#xD;
      use is reliable and reproducible. Today, it is clinical routine to not remove further lymph&#xD;
      nodes from the axilla (arm pit) in case the sentinel node (which is the first lymph node/s&#xD;
      reached by lymphatic flow from the breast) is free of tumor deposits. It is also routine to&#xD;
      leave remaining lymph nodes behind in case the sentinel node contains a minimal cluster of&#xD;
      tumor cells, called isolated tumor cells (formerly submicrometastasis). Even in slightly&#xD;
      larger tumor deposits, so called micrometastasis (up to 2 mm in size), it has been shown that&#xD;
      a completion axillary clearance (removal of further lymph nodes from the arm pit) does not&#xD;
      contribute to a better survival. Data from a randomized study indicate that it seems safe to&#xD;
      omit axillary clearance even if the sentinel node biopsy shows up to 2 nodes with tumor&#xD;
      deposits over 2 mm in size (macrometastasis). These studies have changed clinical practice in&#xD;
      many countries, however, it is still debated whether it is safe to omit axillary clearance in&#xD;
      the case of sentinel node macrometastasis due to under-recruitment in the aforementioned&#xD;
      study. The rationale for omitting extensive axillary surgery is the avoidance of&#xD;
      postoperative morbidity such as arm lymphedema, loss of sensation, pain and swelling.&#xD;
&#xD;
      The hypothesis is that refraining from axillary clearance in breast cancer patients with 1-2&#xD;
      sentinel nodes with macrometastasis will not worsen breast cancer-specific survival by more&#xD;
      than a maximum of 2.5% after 5 years.&#xD;
&#xD;
      This study is a prospective international randomized trial including 3500 patients.&#xD;
&#xD;
      Breast cancer patients without signs of axillary nodal involvement will be eligible for&#xD;
      sentinel node biopsy. Those who are found to have up to two sentinel node containing&#xD;
      macrometastasis will be informed about this trial Those wishing to participate will be&#xD;
      randomized to either undergo further axillary surgery (clearance) or not. Outcome measures&#xD;
      are breast cancer-specific survival, disease-free survival, axillary recurrence rate and&#xD;
      overall survival.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Details can be found on www.senomac.se&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 27, 2015</start_date>
  <completion_date type="Anticipated">December 31, 2026</completion_date>
  <primary_completion_date type="Actual">December 31, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>breast cancer-specific survival</measure>
    <time_frame>up to 15 years</time_frame>
    <description>death due to breast cancer in both arms measured at a median follow-up of 5, 10 and 15 years</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>disease-free survival</measure>
    <time_frame>5, 10 and 15 years</time_frame>
    <description>Breast cancer recurrence rate in both arms after a median follow-up of 5, 10 and 15 years</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>axillary recurrence rate</measure>
    <time_frame>5, 10 and 15 years</time_frame>
    <description>The rate of axillary relapse in specific after a median follow-up of 5, 10 and 15 years</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>overall survival</measure>
    <time_frame>5, 10 and 15 years</time_frame>
    <description>The rate of overall deaths after a median follow-up of 5, 10 and 15 years</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">2700</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Axillary clearance</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Patients in this arm will be treated by completion axillary clearance after a sentinel node biopsy showing 1-2 nodes with macrometastasis</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No axillary clearance</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients in this arm will not undergo further axillary surgery after a sentinel node biopsy showing 1-2 nodes with macrometastasis</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Omission of axillary clearance</intervention_name>
    <description>The intervention is the omission of completion axillary clearance after the detection of sentinel node macrometastasis</description>
    <arm_group_label>No axillary clearance</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with invasive breast cancer (T1-T3)&#xD;
&#xD;
          -  N0 on palpation&#xD;
&#xD;
          -  Preoperative ultrasound performed&#xD;
&#xD;
          -  Pathology report shows macrometastasis in 1-2 sentinel lymph nodes&#xD;
&#xD;
          -  Patients undergo breast-conserving therapy or mastectomy&#xD;
&#xD;
          -  The patient must have provided oral and written consent&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Metastases outside of the ipsilateral axilla&#xD;
&#xD;
          -  Prior history of invasive breast cancer&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Bilateral breast cancer if one side meets exclusion criteria&#xD;
&#xD;
          -  Medical contraindication for radiotherapy or systemic treatment&#xD;
&#xD;
          -  Inability to absorb or understand the meaning of the study information; for example,&#xD;
             through disability, inadequate language skills or dementia.&#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>Jana de Boniface, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Karolinska Institutet</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jan Frisell, Professor</last_name>
    <role>Study Chair</role>
    <affiliation>Karolinska University Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Leif Bergkvist, Professor</last_name>
    <role>Study Chair</role>
    <affiliation>Central Hospital Västerås</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Yvette Andersson, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Central Hospital Västerås</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Lisa Ryden, Professor</last_name>
    <role>Study Chair</role>
    <affiliation>Lund University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Malin Sund, Professor</last_name>
    <role>Study Chair</role>
    <affiliation>Umeå University Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Olofsson Roger, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Sahlgrenska University Hospital, Sweden</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Johan Ahlgren, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Region Örebro County</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Dan Lundstedt, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Sahlgrenska University Hospital, Sweden</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Peer Christiansen, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Aarhus University Hospital, Denmark</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Tove Tvedskov Filtenborg, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Rigshospitalet Copenhagen, Dnmark</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Michalis Kontos, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>University of Athens</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Birgitte Offersen, Professor</last_name>
    <role>Study Chair</role>
    <affiliation>University of Aarhus</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Thorsten Kühn, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Klinikum Esslingen</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Toralf Reimer, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Universität Rostock</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Oreste Gentilini</last_name>
    <role>Principal Investigator</role>
    <affiliation>San Raffaele Hospital, Milano</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Roland Reitsamer</last_name>
    <role>Principal Investigator</role>
    <affiliation>Universitätsklinikum Salzburg</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sygehus Sonderjylland</name>
      <address>
        <city>Aabenraa</city>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aalborg University Hospital</name>
      <address>
        <city>Aalborg</city>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aarhus University Hospital</name>
      <address>
        <city>Aarhus</city>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rigshospitalet</name>
      <address>
        <city>Copenhagen</city>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sydvestjysk Sygehus</name>
      <address>
        <city>Esbjerg</city>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sygehus Lillebaelt</name>
      <address>
        <city>Lillebaelt</city>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Odense University Hospital</name>
      <address>
        <city>Odense</city>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Randers Regionshospitalet</name>
      <address>
        <city>Randers</city>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regionshospitalet Viborg</name>
      <address>
        <city>Viborg</city>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Athens University Hospital</name>
      <address>
        <city>Athens</city>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gävle sjukhus</name>
      <address>
        <city>Gävle</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sahlgrenska University Hospital</name>
      <address>
        <city>Göteborg</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hallands sjukhus</name>
      <address>
        <city>Halmstad</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Helsingborg lasarett</name>
      <address>
        <city>Helsingborg</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Länssjukhuset Ryhov</name>
      <address>
        <city>Jönköping</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kalmar sjukhus</name>
      <address>
        <city>Kalmar</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Blekinge sjukhuset</name>
      <address>
        <city>Karlskrona</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Karlstad sjukhus</name>
      <address>
        <city>Karlstad</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Central Hospital Kristianstad</name>
      <address>
        <city>Kristianstad</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Linköping University Hospital</name>
      <address>
        <city>Linköping</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Malmö/Lund University Hospital</name>
      <address>
        <city>Lund</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Skaraborgs sjukhus</name>
      <address>
        <city>Skövde/Lidköping</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Karolinska University Hospital</name>
      <address>
        <city>Stockholm</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southern Gerenal Hospital</name>
      <address>
        <city>Stockholm</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Görans Hospital</name>
      <address>
        <city>Stockholm</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sundsvall länssjukhus</name>
      <address>
        <city>Sundsvall</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uddevalla sjukhus</name>
      <address>
        <city>Uddevalla</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Umeå University Hospital</name>
      <address>
        <city>Umeå</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Akademiska Sjukhuset</name>
      <address>
        <city>Uppsala</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Varbergs sjukhus</name>
      <address>
        <city>Varberg</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Västervik Hospital</name>
      <address>
        <city>Västervik</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Västerås Central Hospital</name>
      <address>
        <city>Västerås</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Örebro University Hospital</name>
      <address>
        <city>Örebro</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
    <country>Greece</country>
    <country>Sweden</country>
  </location_countries>
  <link>
    <url>http://senomac.se</url>
    <description>study homepage</description>
  </link>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>September 11, 2014</study_first_submitted>
  <study_first_submitted_qc>September 12, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 15, 2014</study_first_posted>
  <last_update_submitted>April 4, 2022</last_update_submitted>
  <last_update_submitted_qc>April 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 6, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Karolinska Institutet</investigator_affiliation>
    <investigator_full_name>Jana de Boniface</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>sentinel node biopsy, lymph node metastasis, survival</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <study_docs>
    <study_doc>
      <doc_type>Study Protocol</doc_type>
      <doc_url>http://senomac.se/Home/study%20protocol.html</doc_url>
      <doc_comment>Study protocol and patient information (English)</doc_comment>
    </study_doc>
  </study_docs>
  <!-- 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/NCT02240472
org study id: SENOMAC
nct id: NCT02240472
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
Since the introduction of sentinel node biopsy in breast cancer, it has become clear that its
      use is reliable and reproducible. Today, it is clinical routine to not remove further lymph
      nodes from the axilla (arm pit) in case the sentinel node (which is the first lymph node/s
      reached by lymphatic flow from the breast) is free of tumor deposits. It is also routine to
      leave remaining lymph nodes behind in case the sentinel node contains a minimal cluster of
      tumor cells, called isolated tumor cells (formerly submicrometastasis). Even in slightly
      larger tumor deposits, so called micrometastasis (up to 2 mm in size), it has been shown that
      a completion axillary clearance (removal of further lymph nodes from the arm pit) does not
      contribute to a better survival. Data from a randomized study indicate that it seems safe to
      omit axillary clearance even if the sentinel node biopsy shows up to 2 nodes with tumor
      deposits over 2 mm in size (macrometastasis). These studies have changed clinical practice in
      many countries, however, it is still debated whether it is safe to omit axillary clearance in
      the case of sentinel node macrometastasis due to under-recruitment in the aforementioned
      study. The rationale for omitting extensive axillary surgery is the avoidance of
      postoperative morbidity such as arm lymphedema, loss of sensation, pain and swelling.

      The hypothesis is that refraining from axillary clearance in breast cancer patients with 1-2
      sentinel nodes with macrometastasis will not worsen breast cancer-specific survival by more
      than a maximum of 2.5% after 5 years.

      This study is a prospective international randomized trial including 3500 patients.

      Breast cancer patients without signs of axillary nodal involvement will be eligible for
      sentinel node biopsy. Those who are found to have up to two sentinel node containing
      macrometastasis will be informed about this trial Those wishing to participate will be
      randomized to either undergo further axillary surgery (clearance) or not. Outcome measures
      are breast cancer-specific survival, disease-free survival, axillary recurrence rate and
      overall survival.
Details can be found on www.senomac.se
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: breast cancer-specific survival
time frame: up to 15 years
description: death due to breast cancer in both arms measured at a median follow-up of 5, 10 and 15 years
measure: disease-free survival
time frame: 5, 10 and 15 years
description: Breast cancer recurrence rate in both arms after a median follow-up of 5, 10 and 15 years
measure: axillary recurrence rate
time frame: 5, 10 and 15 years
description: The rate of axillary relapse in specific after a median follow-up of 5, 10 and 15 years
measure: overall survival
time frame: 5, 10 and 15 years
description: The rate of overall deaths after a median follow-up of 5, 10 and 15 years
arm group label: Axillary clearance
arm group type: No Intervention
description: Patients in this arm will be treated by completion axillary clearance after a sentinel node biopsy showing 1-2 nodes with macrometastasis
arm group label: No axillary clearance
arm group type: Experimental
description: Patients in this arm will not undergo further axillary surgery after a sentinel node biopsy showing 1-2 nodes with macrometastasis
intervention type: Procedure
intervention name: Omission of axillary clearance
description: The intervention is the omission of completion axillary clearance after the detection of sentinel node macrometastasis
arm group label: No axillary clearance
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jana de Boniface, PhD
role: Principal Investigator
affiliation: Karolinska Institutet
last name: Jan Frisell, Professor
role: Study Chair
affiliation: Karolinska University Hospital
last name: Leif Bergkvist, Professor
role: Study Chair
affiliation: Central Hospital Västerås
last name: Yvette Andersson, PhD
role: Study Chair
affiliation: Central Hospital Västerås
last name: Lisa Ryden, Professor
role: Study Chair
affiliation: Lund University
last name: Malin Sund, Professor
role: Study Chair
affiliation: Umeå University Hospital
last name: Olofsson Roger, PhD
role: Study Chair
affiliation: Sahlgrenska University Hospital, Sweden
last name: Johan Ahlgren, PhD
role: Study Chair
affiliation: Region Örebro County
last name: Dan Lundstedt, PhD
role: Study Chair
affiliation: Sahlgrenska University Hospital, Sweden
last name: Peer Christiansen, Professor
role: Principal Investigator
affiliation: Aarhus University Hospital, Denmark
last name: Tove Tvedskov Filtenborg, MD
role: Study Chair
affiliation: Rigshospitalet Copenhagen, Dnmark
last name: Michalis Kontos, PhD
role: Study Chair
affiliation: University of Athens
last name: Birgitte Offersen, Professor
role: Study Chair
affiliation: University of Aarhus
last name: Thorsten Kühn, Professor
role: Principal Investigator
affiliation: Klinikum Esslingen
last name: Toralf Reimer, Professor
role: Principal Investigator
affiliation: Universität Rostock
last name: Oreste Gentilini
role: Principal Investigator
affiliation: San Raffaele Hospital, Milano
last name: Roland Reitsamer
role: Principal Investigator
affiliation: Universitätsklinikum Salzburg
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country: Denmark
country: Greece
country: Sweden
url: http://senomac.se
description: study homepage
responsible party type: Principal Investigator
investigator affiliation: Karolinska Institutet
investigator full name: Jana de Boniface
investigator title: Associate Professor
mesh term: Breast Neoplasms
study doc: 