<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/NCT01717131</url>
  </required_header>
  <id_info>
    <org_study_id>SERC / IPC 2012-001</org_study_id>
    <nct_id>NCT01717131</nct_id>
  </id_info>
  <brief_title>Axillary Node Dissection Versus no Dissection in Breast Cancer With Positive Sentinel Lymph Node</brief_title>
  <official_title>A Non Inferiority Randomized Multicenter Phase III Trial of Axillary Node Dissection Versus no Axillary Node Dissection in Case of Positive Sentinel Lymph Node in Invasive Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institut Paoli-Calmettes</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Institut Paoli-Calmettes</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Data from cohorts, prospective studies and one randomized trial (ASCOG Z0011) support the&#xD;
      hypothesis that omission of additional axillary dissection in case of positive sentinel node&#xD;
      has a limited impact on overall survival and relapse free survival. However, these data are&#xD;
      not sufficient enough to recommend, as a standard of care, to avoid axillary dissection in&#xD;
      case of positive sentinel node. The ASCOG Z0011 trial has been closed before the end of&#xD;
      inclusions and the predefined non inferiority margin was found to be too large (5% difference&#xD;
      at 5 years for primary endpoint).&#xD;
&#xD;
      Prospective randomized trial is then urgently mandatory before omission of axillary node&#xD;
      dissection becomes a usual practice without a sufficient scientific level of proof. Indeed,&#xD;
      in several reviews, the rate of omission of axillary node dissection in case of&#xD;
      micrometastasis increased (Bilimoria) despite any strong proof has been demonstrated.&#xD;
&#xD;
      The omission of axillary node dissection in case of positive sentinel node may have strong&#xD;
      practical impacts on patients but also on medical and economical aspects: in avoiding a&#xD;
      prolonged hospitalisation, secondary morbidities due to axillary dissection requiring&#xD;
      secondary care and their costs, as well as costs for secondary axillary dissection (14 to 25%&#xD;
      in case of positive sentinel node) and finally shortening surgery duration.&#xD;
&#xD;
      The main investigator propose a Non Inferiority Randomized Multicenter Phase III Trial of&#xD;
      Axillary Node Dissection Versus no Axillary Node Dissection in Case of Positive Sentinel&#xD;
      Lymph Node in Invasive Breast Cancer&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date>July 2012</start_date>
  <completion_date type="Anticipated">July 2028</completion_date>
  <primary_completion_date type="Anticipated">July 2028</primary_completion_date>
  <phase>Phase 3</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>Disease Free survival</measure>
    <time_frame>Time to relapse or progression up to 10 years</time_frame>
    <description>time from randomization to relapse or death.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>axillary recurrence rate</measure>
    <time_frame>Time to local relapse up to 10 years</time_frame>
    <description>Estimate the incidence of axillary recurrence after surgery followed by axillary dissection or after surgery alone.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Time to death up to 10 years</time_frame>
    <description>Time from randomization to date of death</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">3000</enrollment>
  <condition>Invasive Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Surgery for standard axillary node dissection</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Standard axillary dissection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No axillary lymph node dissection</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>No surgery of axillary lymph node In this study, the absence of surgery is the experimental arm (non-inferiority trial)</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Surgery for standard axillary node dissection</intervention_name>
    <arm_group_label>Surgery for standard axillary node dissection</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>No axillary lymph node dissection</intervention_name>
    <description>No surgery on axillary lymph node</description>
    <arm_group_label>No axillary lymph node dissection</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. - Patient aged 18 years and above,&#xD;
&#xD;
          2. - Patient with invasive breast cancer histologically proven or cytologically proven by&#xD;
             fine needle biopsy,&#xD;
&#xD;
          3. - Patient with a unifocal tumor T0 - T1 - T2 up to 5 cm (clinical or in imagery),&#xD;
             without previous therapy (neoadjuvant chemotherapy or hormone therapy),&#xD;
&#xD;
          4. - Patient with clinical N0 status,&#xD;
&#xD;
          5. - Absence of clinically detectable metastases known,&#xD;
&#xD;
        6- Patients for whom conservative surgery with sentinel lymph node (SLN) technique is&#xD;
        feasible from the start in terms of carcinologic,&#xD;
&#xD;
        7 -All patients with lymph node involvement (GS+), whatever the size of the metastasis&#xD;
        (macro-metastasis, micro-metastasis, cellular cluster or isolated tumor cells),&#xD;
&#xD;
        8 - Patient affiliated to a social security system or benefiting from such a system,&#xD;
&#xD;
        9 - Signed consent to participate.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. - Tumor of more than 5 cm&#xD;
&#xD;
          2. - Indication of neoadjuvant therapy by chemotherapy or hormone therapy&#xD;
&#xD;
          3. - History of breast cancer (ipsilateral, ie recurrence, or contralateral breast)&#xD;
&#xD;
          4. - History of any other invasive cancer other than a past cutaneous cancer correctly&#xD;
             treated&#xD;
&#xD;
          5. - Initial metastatic disease known&#xD;
&#xD;
          6. - Presence of clinical axillary adenopathy&#xD;
&#xD;
          7. - Contra-indication to surgical excision&#xD;
&#xD;
          8. - Contra-indication to the SLN technique&#xD;
&#xD;
          9. - Pregnant women, of child-bearing potential, or lactating women&#xD;
&#xD;
        10- Patient deprived of liberty or under supervision of a guardian&#xD;
&#xD;
        11- Impossibility to undergo medical examinations of the study for geographical, social or&#xD;
        psychological reasons.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gilles HOUVENAEGHEL, MD, PHD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institut Paoli-Calmettes</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Dominique GENRE, MD</last_name>
    <phone>33 (0)4 91 22 37 78</phone>
    <email>drci.up@ipc.unicancer.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Sandra COURNIER</last_name>
    <phone>33 (0)4 91 22 37 78</phone>
    <email>drci.up@ipc.unicancer.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Gilles HOUVENAEGHEL, PHD</name>
      <address>
        <city>Marseille</city>
        <zip>13009</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gilles HOUVENAEGHEL, PhD</last_name>
      <phone>33(0)491223778</phone>
      <email>drci.up@ipc.unicancer.fr</email>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <link>
    <url>http://www.institutpaolicalmettes.fr</url>
    <description>official web site of the sponsor</description>
  </link>
  <reference>
    <citation>Giuliano AE, Ballman KV, McCall L, Beitsch PD, Brennan MB, Kelemen PR, Ollila DW, Hansen NM, Whitworth PW, Blumencranz PW, Leitch AM, Saha S, Hunt KK, Morrow M. Effect of Axillary Dissection vs No Axillary Dissection on 10-Year Overall Survival Among Women With Invasive Breast Cancer and Sentinel Node Metastasis: The ACOSOG Z0011 (Alliance) Randomized Clinical Trial. JAMA. 2017 Sep 12;318(10):918-926. doi: 10.1001/jama.2017.11470.</citation>
    <PMID>28898379</PMID>
  </reference>
  <reference>
    <citation>Donker M, van Tienhoven G, Straver ME, Meijnen P, van de Velde CJ, Mansel RE, Cataliotti L, Westenberg AH, Klinkenbijl JH, Orzalesi L, Bouma WH, van der Mijle HC, Nieuwenhuijzen GA, Veltkamp SC, Slaets L, Duez NJ, de Graaf PW, van Dalen T, Marinelli A, Rijna H, Snoj M, Bundred NJ, Merkus JW, Belkacemi Y, Petignat P, Schinagl DA, Coens C, Messina CG, Bogaerts J, Rutgers EJ. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial. Lancet Oncol. 2014 Nov;15(12):1303-10. doi: 10.1016/S1470-2045(14)70460-7. Epub 2014 Oct 15.</citation>
    <PMID>25439688</PMID>
  </reference>
  <reference>
    <citation>Jagsi R, Chadha M, Moni J, Ballman K, Laurie F, Buchholz TA, Giuliano A, Haffty BG. Radiation field design in the ACOSOG Z0011 (Alliance) Trial. J Clin Oncol. 2014 Nov 10;32(32):3600-6. doi: 10.1200/JCO.2014.56.5838. Epub 2014 Aug 18.</citation>
    <PMID>25135994</PMID>
  </reference>
  <results_reference>
    <citation>Houvenaeghel G, Cohen M, Raro P, De Troyer J, de Lara CT, Gimbergues P, Gauthier T, Faure-Virelizier C, Vaini-Cowen V, Lantheaume S, Regis C, Darai E, Ceccato V, D'Halluin G, Del Piano F, Villet R, Jouve E, Beedassy B, Theret P, Gabelle P, Zinzindohoue C, Opinel P, Marsollier-Ferrer C, Dhainaut-Speyer C, Colombo PE, Lambaudie E, Tallet A, Boher JM; Others investigators (SERC trial group). Overview of the pathological results and treatment characteristics in the first 1000 patients randomized in the SERC trial: axillary dissection versus no axillary dissection in patients with involved sentinel node. BMC Cancer. 2018 Nov 21;18(1):1153. doi: 10.1186/s12885-018-5053-7.</citation>
    <PMID>30463611</PMID>
  </results_reference>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>October 19, 2012</study_first_submitted>
  <study_first_submitted_qc>October 26, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 30, 2012</study_first_posted>
  <last_update_submitted>January 17, 2020</last_update_submitted>
  <last_update_submitted_qc>January 17, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Invasive breast cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_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/NCT01717131
org study id: SERC / IPC 2012-001
nct id: NCT01717131
lead sponsor: 
has dmc: No
Data from cohorts, prospective studies and one randomized trial (ASCOG Z0011) support the
      hypothesis that omission of additional axillary dissection in case of positive sentinel node
      has a limited impact on overall survival and relapse free survival. However, these data are
      not sufficient enough to recommend, as a standard of care, to avoid axillary dissection in
      case of positive sentinel node. The ASCOG Z0011 trial has been closed before the end of
      inclusions and the predefined non inferiority margin was found to be too large (5% difference
      at 5 years for primary endpoint).

      Prospective randomized trial is then urgently mandatory before omission of axillary node
      dissection becomes a usual practice without a sufficient scientific level of proof. Indeed,
      in several reviews, the rate of omission of axillary node dissection in case of
      micrometastasis increased (Bilimoria) despite any strong proof has been demonstrated.

      The omission of axillary node dissection in case of positive sentinel node may have strong
      practical impacts on patients but also on medical and economical aspects: in avoiding a
      prolonged hospitalisation, secondary morbidities due to axillary dissection requiring
      secondary care and their costs, as well as costs for secondary axillary dissection (14 to 25%
      in case of positive sentinel node) and finally shortening surgery duration.

      The main investigator propose a Non Inferiority Randomized Multicenter Phase III Trial of
      Axillary Node Dissection Versus no Axillary Node Dissection in Case of Positive Sentinel
      Lymph Node in Invasive Breast Cancer
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Disease Free survival
time frame: Time to relapse or progression up to 10 years
description: time from randomization to relapse or death.
measure: axillary recurrence rate
time frame: Time to local relapse up to 10 years
description: Estimate the incidence of axillary recurrence after surgery followed by axillary dissection or after surgery alone.
measure: Overall survival
time frame: Time to death up to 10 years
description: Time from randomization to date of death
arm group label: Surgery for standard axillary node dissection
arm group type: Active Comparator
description: Standard axillary dissection
arm group label: No axillary lymph node dissection
arm group type: Experimental
description: No surgery of axillary lymph node In this study, the absence of surgery is the experimental arm (non-inferiority trial)
intervention type: Procedure
intervention name: Surgery for standard axillary node dissection
arm group label: Surgery for standard axillary node dissection
intervention type: Other
intervention name: No axillary lymph node dissection
description: No surgery on axillary lymph node
arm group label: No axillary lymph node dissection
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gilles HOUVENAEGHEL, MD, PHD
role: Principal Investigator
affiliation: Institut Paoli-Calmettes
last name: Dominique GENRE, MD
phone: 33 (0)4 91 22 37 78
email: drci.up@ipc.unicancer.fr
last name: Sandra COURNIER
phone: 33 (0)4 91 22 37 78
email: drci.up@ipc.unicancer.fr
facility: 
status: Recruiting
contact: 
country: France
url: http://www.institutpaolicalmettes.fr
description: official web site of the sponsor
citation: Giuliano AE, Ballman KV, McCall L, Beitsch PD, Brennan MB, Kelemen PR, Ollila DW, Hansen NM, Whitworth PW, Blumencranz PW, Leitch AM, Saha S, Hunt KK, Morrow M. Effect of Axillary Dissection vs No Axillary Dissection on 10-Year Overall Survival Among Women With Invasive Breast Cancer and Sentinel Node Metastasis: The ACOSOG Z0011 (Alliance) Randomized Clinical Trial. JAMA. 2017 Sep 12;318(10):918-926. doi: 10.1001/jama.2017.11470.
PMID: 28898379
citation: Donker M, van Tienhoven G, Straver ME, Meijnen P, van de Velde CJ, Mansel RE, Cataliotti L, Westenberg AH, Klinkenbijl JH, Orzalesi L, Bouma WH, van der Mijle HC, Nieuwenhuijzen GA, Veltkamp SC, Slaets L, Duez NJ, de Graaf PW, van Dalen T, Marinelli A, Rijna H, Snoj M, Bundred NJ, Merkus JW, Belkacemi Y, Petignat P, Schinagl DA, Coens C, Messina CG, Bogaerts J, Rutgers EJ. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial. Lancet Oncol. 2014 Nov;15(12):1303-10. doi: 10.1016/S1470-2045(14)70460-7. Epub 2014 Oct 15.
PMID: 25439688
citation: Jagsi R, Chadha M, Moni J, Ballman K, Laurie F, Buchholz TA, Giuliano A, Haffty BG. Radiation field design in the ACOSOG Z0011 (Alliance) Trial. J Clin Oncol. 2014 Nov 10;32(32):3600-6. doi: 10.1200/JCO.2014.56.5838. Epub 2014 Aug 18.
PMID: 25135994
citation: Houvenaeghel G, Cohen M, Raro P, De Troyer J, de Lara CT, Gimbergues P, Gauthier T, Faure-Virelizier C, Vaini-Cowen V, Lantheaume S, Regis C, Darai E, Ceccato V, D'Halluin G, Del Piano F, Villet R, Jouve E, Beedassy B, Theret P, Gabelle P, Zinzindohoue C, Opinel P, Marsollier-Ferrer C, Dhainaut-Speyer C, Colombo PE, Lambaudie E, Tallet A, Boher JM; Others investigators (SERC trial group). Overview of the pathological results and treatment characteristics in the first 1000 patients randomized in the SERC trial: axillary dissection versus no axillary dissection in patients with involved sentinel node. BMC Cancer. 2018 Nov 21;18(1):1153. doi: 10.1186/s12885-018-5053-7.
PMID: 30463611
responsible party type: Sponsor
mesh term: Breast Neoplasms