<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/NCT04436809</url>
  </required_header>
  <id_info>
    <org_study_id>INT180/13</org_study_id>
    <nct_id>NCT04436809</nct_id>
  </id_info>
  <brief_title>Sentinel Node Biopsy Alone or With Axillary Dissection After Primary Chemotherapy</brief_title>
  <official_title>Sentinel Node Biopsy Alone or With Axillary Dissection in cT2 cN0/1 Breast Cancer Patients After Primary Chemotherapy: a Prospective Interventional Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fondazione IRCCS Istituto Nazionale dei Tumori, Milano</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fondazione IRCCS Istituto Nazionale dei Tumori, Milano</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Many doctors believe that breast cancer patients scheduled for pre-operative chemotherapy&#xD;
      whose cancer has spread to the axilla (determined by palpation plus ultrasound) should not&#xD;
      receive sentinel node biopsy after chemotherapy, but proceed directly to removal of all the&#xD;
      axillary lymph nodes.&#xD;
&#xD;
      In this study, breast cancer patients with operable medium-size cancer (T2) scheduled for&#xD;
      pre-operative chemotherapy, and a disease-free or a metastatic axilla, are prospectively&#xD;
      assigned to receive sentinel node biopsy as part of their post-chemotherapy surgical&#xD;
      treatment (whose main aim is to remove the cancer in the breast).&#xD;
&#xD;
      Irrespective of whether the axilla is disease-free or metastatic before chemotherapy, if the&#xD;
      removed sentinel nodes are disease-free on histological examination (pN0) after chemotherapy,&#xD;
      then no further axillary treatment is given. If however the sentinel nodes contain cancer,&#xD;
      then the other axillary lymph nodes will be removed surgically.&#xD;
&#xD;
      The study hypothesis is that, irrespective of whether the axilla is disease-free or&#xD;
      metastatic before chemotherapy, patients with negative axillary sentinel nodes on&#xD;
      histological examination (pN0) after chemotherapy, and who are no given further axillary&#xD;
      treatment, will do as well as pN1 patients whose axillary lymph nodes are completely removed&#xD;
      (a more aggressive treatment).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2007</start_date>
  <completion_date type="Actual">December 31, 2015</completion_date>
  <primary_completion_date type="Actual">December 31, 2015</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall Survival (OS) and Disease-Free Survival (DFS)</measure>
    <time_frame>Ten years</time_frame>
    <description>DFS and OS are reckoned from date of surgery. DFS is time to recurrence or death, whichever occurred first. OS is time to death for any cause. Time is censored for living patients who are event-free at most recent follow up. OS and DFS curves are estimated using the Kaplan-Meier method and compared using the log-rank test. To compare DFS and OS in the SNB only and SNB + AD groups, propensity scores are estimated to account for bias due to non-random assignment to SNB vs SNB + AD</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rate of axillary failure in those receiving only sentinel node biopsy</measure>
    <time_frame>Ten years</time_frame>
    <description>In patients given only sentinel node biopsy the proportion of patients who develop disease in the axilla will be calculated.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Assessment of pathological response to primary chemotherapy as predictor of outcome</measure>
    <time_frame>Ten years</time_frame>
    <description>The response of the cancer to primary chemotherapy (complete response, partial response, stable disease, disease progression) will be related to overall outcomes.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">353</enrollment>
  <condition>Breast Neoplasm Female</condition>
  <arm_group>
    <arm_group_label>SNB only</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>cT2 patients scheduled for primary chemotherapy (with or without a clinically involved axilla - cN0/1) who have disease-free sentinel nodes (pN0) after primary chemotherapy, are directed to &quot;SNB only&quot;: i.e. no further treatment to the axilla.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SNB + AD</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>cT2 patients scheduled for primary chemotherapy (with or without a clinically involved axilla - cN0/1) who have metastatic sentinel nodes (pN1) on sentinel node biopsy (SNB) will undergo axillary dissection (AD) i.e. surgical removal of most axillary lymph nodes.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Sentinel Node Biopsy</intervention_name>
    <description>Colloidal radiotracer (99Tc) is injected into the breast near the cancer. The radiotracer moves in the lymph ducts to accumulate in the first lymph nodes (almost always in the axilla) to receive lymph from the breast area containing the cancer. Lymphoscintigraphy is used to check for the presence of radioactivity in the axilla. Some hours later, during breast surgery, a radioactivity-detecting probe is used to identify &quot;hot&quot; lymph nodes (sentinel nodes) and aid their surgical removal from the axilla. These nodes are examined histologically (intraoperatively) for the presence of cancer. If they are disease-free the axilla will be left intact (no further axillary treatment given); if they contain cancer most lymph nodes in the axilla will be removed surgically (axillary dissection).</description>
    <arm_group_label>SNB + AD</arm_group_label>
    <arm_group_label>SNB only</arm_group_label>
    <other_name>Sentinel Lymph Node Biopsy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Axillary Dissection</intervention_name>
    <description>Axillary dissection is the surgical removal of all Berg level I and II lymph nodes present in the axilla. The operation is carried out, at our Institute, during the surgery to treat the cancer in the breast (either breast-conserving surgery - quadrantectomy, or mastectomy).</description>
    <arm_group_label>SNB + AD</arm_group_label>
    <other_name>Axillary Lymph Node Dissection</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  cT2 cN0/1 breast cancer&#xD;
&#xD;
          -  Scheduled for neoadjuvant chemotherapy,&#xD;
&#xD;
          -  Informed consent,&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous malignancy at another site&#xD;
&#xD;
          -  Synchronous breast cancer at diagnosis&#xD;
&#xD;
          -  Distant metastasis at diagnosis&#xD;
&#xD;
          -  Clinically involved axilla (cN1) after neoadjuvant chemotherapy&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Yes</gender_description>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gabriele Martelli, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fondazione IRCCS Istituto Nazionale dei Tumori, Milano</affiliation>
  </overall_official>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 14, 2020</study_first_submitted>
  <study_first_submitted_qc>June 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 18, 2020</study_first_posted>
  <last_update_submitted>June 18, 2020</last_update_submitted>
  <last_update_submitted_qc>June 18, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Fondazione IRCCS Istituto Nazionale dei Tumori, Milano</investigator_affiliation>
    <investigator_full_name>Gabriele Martelli</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Breast cancer</keyword>
  <keyword>Sentinel node biopsy</keyword>
  <keyword>Neoadjuvant chemotherapy</keyword>
  <keyword>Axillary dissection</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>
  </patient_data>
  <!-- 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/NCT04436809
org study id: INT180/13
nct id: NCT04436809
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Many doctors believe that breast cancer patients scheduled for pre-operative chemotherapy
      whose cancer has spread to the axilla (determined by palpation plus ultrasound) should not
      receive sentinel node biopsy after chemotherapy, but proceed directly to removal of all the
      axillary lymph nodes.

      In this study, breast cancer patients with operable medium-size cancer (T2) scheduled for
      pre-operative chemotherapy, and a disease-free or a metastatic axilla, are prospectively
      assigned to receive sentinel node biopsy as part of their post-chemotherapy surgical
      treatment (whose main aim is to remove the cancer in the breast).

      Irrespective of whether the axilla is disease-free or metastatic before chemotherapy, if the
      removed sentinel nodes are disease-free on histological examination (pN0) after chemotherapy,
      then no further axillary treatment is given. If however the sentinel nodes contain cancer,
      then the other axillary lymph nodes will be removed surgically.

      The study hypothesis is that, irrespective of whether the axilla is disease-free or
      metastatic before chemotherapy, patients with negative axillary sentinel nodes on
      histological examination (pN0) after chemotherapy, and who are no given further axillary
      treatment, will do as well as pN1 patients whose axillary lymph nodes are completely removed
      (a more aggressive treatment).
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Survival (OS) and Disease-Free Survival (DFS)
time frame: Ten years
description: DFS and OS are reckoned from date of surgery. DFS is time to recurrence or death, whichever occurred first. OS is time to death for any cause. Time is censored for living patients who are event-free at most recent follow up. OS and DFS curves are estimated using the Kaplan-Meier method and compared using the log-rank test. To compare DFS and OS in the SNB only and SNB + AD groups, propensity scores are estimated to account for bias due to non-random assignment to SNB vs SNB + AD
measure: Rate of axillary failure in those receiving only sentinel node biopsy
time frame: Ten years
description: In patients given only sentinel node biopsy the proportion of patients who develop disease in the axilla will be calculated.
measure: Assessment of pathological response to primary chemotherapy as predictor of outcome
time frame: Ten years
description: The response of the cancer to primary chemotherapy (complete response, partial response, stable disease, disease progression) will be related to overall outcomes.
arm group label: SNB only
arm group type: Other
description: cT2 patients scheduled for primary chemotherapy (with or without a clinically involved axilla - cN0/1) who have disease-free sentinel nodes (pN0) after primary chemotherapy, are directed to "SNB only": i.e. no further treatment to the axilla.
arm group label: SNB + AD
arm group type: Other
description: cT2 patients scheduled for primary chemotherapy (with or without a clinically involved axilla - cN0/1) who have metastatic sentinel nodes (pN1) on sentinel node biopsy (SNB) will undergo axillary dissection (AD) i.e. surgical removal of most axillary lymph nodes.
intervention type: Procedure
intervention name: Sentinel Node Biopsy
description: Colloidal radiotracer (99Tc) is injected into the breast near the cancer. The radiotracer moves in the lymph ducts to accumulate in the first lymph nodes (almost always in the axilla) to receive lymph from the breast area containing the cancer. Lymphoscintigraphy is used to check for the presence of radioactivity in the axilla. Some hours later, during breast surgery, a radioactivity-detecting probe is used to identify "hot" lymph nodes (sentinel nodes) and aid their surgical removal from the axilla. These nodes are examined histologically (intraoperatively) for the presence of cancer. If they are disease-free the axilla will be left intact (no further axillary treatment given); if they contain cancer most lymph nodes in the axilla will be removed surgically (axillary dissection).
arm group label: SNB + AD
arm group label: SNB only
other name: Sentinel Lymph Node Biopsy
intervention type: Procedure
intervention name: Axillary Dissection
description: Axillary dissection is the surgical removal of all Berg level I and II lymph nodes present in the axilla. The operation is carried out, at our Institute, during the surgery to treat the cancer in the breast (either breast-conserving surgery - quadrantectomy, or mastectomy).
arm group label: SNB + AD
other name: Axillary Lymph Node Dissection
criteria: 
gender: Female
gender based: Yes
gender description: Yes
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Gabriele Martelli, MD
role: Principal Investigator
affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
responsible party type: Principal Investigator
investigator affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
investigator full name: Gabriele Martelli
investigator title: Principal Investigator
mesh term: Breast Neoplasms
sharing ipd: No