<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/NCT02975128</url>
  </required_header>
  <id_info>
    <org_study_id>NL58040.091.16</org_study_id>
    <nct_id>NCT02975128</nct_id>
  </id_info>
  <brief_title>Minimal Invasive Breast Cancer Excision Using the Breast Lesion Excision System Under Ultrasound Guidance</brief_title>
  <acronym>BLES</acronym>
  <official_title>Minimal Invasive Breast Cancer Excision Using the Breast Lesion Excision System Under Ultrasound Guidance</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Radboud University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Canisius-Wilhelmina Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Dutch Cancer Society</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Radboud University Medical Center</source>
  <oversight_info>
    <has_dmc>No</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>
      This study will assess whether it is feasible to remove small breast cancers completely using&#xD;
      the Breast Lesion Excision System under Ultrasound guidance.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Rationale: In the Netherlands, ≥7000 women are operated for small breast cancers yearly. In&#xD;
      this study, we will evaluate under which conditions it is possible to excise small breast&#xD;
      cancers using the Breast Lesion Excision System (BLES) under ultrasound (US) guidance. When&#xD;
      successful, this will allow ambulatory treatment of women with small breast cancers,&#xD;
      improving the cosmetic outcome and quality of life.&#xD;
&#xD;
      Objective: Our study aim is to assess whether it is feasible to remove small breast cancers&#xD;
      completely using the BLES system under US guidance.&#xD;
&#xD;
      Study design: This is a multi-centre, translational clinical phase II study in 125 women with&#xD;
      cancers ≤1.5 cm based upon US measurements, and without mammographic evidence of more&#xD;
      extensive disease (e.g. microcalcifications).&#xD;
&#xD;
      Study population: Women with cancers ≤1.5 cm based upon US measurements, if there is no&#xD;
      mammographic evidence of more extensive disease (e.g. microcalcifications or extensive&#xD;
      architectural distortion), and the tumor lies ≥6 mm away from the dermis, nipple or pectoral&#xD;
      muscle, are eligible for this study.&#xD;
&#xD;
      Intervention: In 125 women with cancers ≤1.5 cm based upon US measurements, and without&#xD;
      mammographic evidence of more extensive disease (e.g. microcalcifications), we will conduct&#xD;
      additional preoperative breast MRI to ascertain lesion size, after informed consent has been&#xD;
      obtained. If the lesion is confirmed ≤1.5 cm on MRI and lying ≥6 mm away from the dermis,&#xD;
      nipple and pectoral muscle, the patient is eligible. Moreover, patients will be asked to fill&#xD;
      out the questionnaire, detailing their risk profile and comorbidity index.&#xD;
&#xD;
      Under general anaesthesia for the normal surgical procedure, the tumor is first removed using&#xD;
      the BLES system under US guidance, through a small skin incision (&lt;1 cm). Next, the normal&#xD;
      surgical procedure is performed, excising the BLES excision cavity and a ≥ 1cm margin of&#xD;
      surrounding tissue, also guided by the US appearance after the BLES procedure. Margin&#xD;
      assessment will be performed separately for the BLES excision and the surgical specimen of&#xD;
      the surrounding tissue.&#xD;
&#xD;
      Main study parameters/endpoints: Main endpoint of the study is the frequency of successful&#xD;
      complete tumor excision by the BLES system, where successful is defined as 'having tumor free&#xD;
      margins, and no residual (in situ) cancer in the surgical specimen'.&#xD;
&#xD;
      Nature and extent of the burden and risks associated with participation, benefit and group&#xD;
      relatedness: Our approach allows to test the feasibility of this highly innovating approach&#xD;
      to remove breast cancer, with minimal negative effects or possible complications.&#xD;
&#xD;
      While there is no direct benefit nor detrimental effect from this study to the patients&#xD;
      participating, the study has large implications for many women, as breast cancer remains the&#xD;
      most common cancer in women, and due to screening, most cancers are small. Further reduction&#xD;
      of the impact of local treatment is still desired as the psychosocial and somatic effects of&#xD;
      breast deformation can be substantial.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Needle production stopped&#xD;
  </why_stopped>
  <start_date type="Actual">February 19, 2018</start_date>
  <completion_date type="Actual">July 31, 2019</completion_date>
  <primary_completion_date type="Actual">July 31, 2019</primary_completion_date>
  <phase>N/A</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Frequency of successful complete tumor excision by the BLES system.</measure>
    <time_frame>Through study completion, an average of two months</time_frame>
    <description>Successful is defined as 'having tumor free margins, and no residual (in situ) cancer in the surgical specimen'.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Quality of the margin evaluation of the biopsy specimen and the eventual surgical specimen.</measure>
    <time_frame>Through study completion, an average of two months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>In biopsy specimen in which the margin is not completely tumor free, but the Dutch criterion for successful surgery is met (no more than focal (4 mm) margin involvement), we will specifically analyse the residual tumor burden in the surgical excision.</measure>
    <time_frame>Through study completion, an average of two months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess in retrospect whether we can predict successful tumor extraction based upon other factors than tumor size alone.</measure>
    <time_frame>2 years</time_frame>
    <description>Parameters categorized in:&#xD;
Patient related variables obtained from a questionnaire&#xD;
Lesion related variables&#xD;
Imaging features&#xD;
Surgical features&#xD;
Histopathological and molecular features from the core biopsy</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">22</enrollment>
  <condition>Breastcancer</condition>
  <arm_group>
    <arm_group_label>Patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>BLES system and conventional lumpectomy</intervention_name>
    <description>Each patient undergoes the same procedure. Under general anaesthesia for the normal surgical procedure, the tumor is first removed using the BLES system under US guidance. Next, the normal surgical procedure is performed, excising the BLES excision cavity and a ≥ 1cm margin of surrounding tissue, also guided by the US appearance after the BLES procedure.</description>
    <arm_group_label>Patients</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Female&#xD;
&#xD;
          -  19 years or older&#xD;
&#xD;
          -  US visible breast cancer with maximum diameter of 15 mm on US&#xD;
&#xD;
          -  Histologically proven invasive breast cancer&#xD;
&#xD;
          -  Willing and able to undergo preoperative breast MRI&#xD;
&#xD;
          -  Able to provide informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Poor US visibility of the breast cancer&#xD;
&#xD;
          -  Breast cancer closer than 6 mm to the dermis, nipple or pectoral muscle.&#xD;
&#xD;
          -  Contra-indications to breast MRI or intravenous contrast administration&#xD;
&#xD;
          -  Contra-indications for the use of diathermia&#xD;
&#xD;
          -  Unable to provide informed consent&#xD;
&#xD;
          -  Patients with breast implants&#xD;
&#xD;
          -  Patients with implanted electronics&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Neoadjuvant chemotherapy&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ritse Mann, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Radboud University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Radboudumc</name>
      <address>
        <city>Nijmegen</city>
        <state>Gelderland</state>
        <zip>6500 HB</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Canisius Wilhelmina Hospital</name>
      <address>
        <city>Nijmegen</city>
        <state>Gelderland</state>
        <zip>6532 SZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <reference>
    <citation>Allen SD, Nerurkar A, Della Rovere GU. The breast lesion excision system (BLES): a novel technique in the diagnostic and therapeutic management of small indeterminate breast lesions? Eur Radiol. 2011 May;21(5):919-24. doi: 10.1007/s00330-010-2000-7. Epub 2011 Jan 15.</citation>
    <PMID>21240608</PMID>
  </reference>
  <reference>
    <citation>Sie A, Bryan DC, Gaines V, Killebrew LK, Kim CH, Morrison CC, Poller WR, Romilly AP, Schilling K, Sung JH. Multicenter evaluation of the breast lesion excision system, a percutaneous, vacuum-assisted, intact-specimen breast biopsy device. Cancer. 2006 Sep 1;107(5):945-9. doi: 10.1002/cncr.22090.</citation>
    <PMID>16874817</PMID>
  </reference>
  <reference>
    <citation>Medjhoul A, Canale S, Mathieu MC, Uzan C, Garbay JR, Dromain C, Balleyguier C. Breast lesion excision sample (BLES biopsy) combining stereotactic biopsy and radiofrequency: is it a safe and accurate procedure in case of BIRADS 4 and 5 breast lesions? Breast J. 2013 Nov-Dec;19(6):590-4. doi: 10.1111/tbj.12184. Epub 2013 Sep 19.</citation>
    <PMID>24102869</PMID>
  </reference>
  <reference>
    <citation>Allen SD, Osin P, Nerurkar A. The radiological excision of high risk and malignant lesions using the INTACT breast lesion excision system. A case series with an imaging follow up of at least 5 years. Eur J Surg Oncol. 2014 Jul;40(7):824-9. doi: 10.1016/j.ejso.2014.03.022. Epub 2014 Apr 2.</citation>
    <PMID>24742589</PMID>
  </reference>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>November 23, 2016</study_first_submitted>
  <study_first_submitted_qc>November 23, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 29, 2016</study_first_posted>
  <last_update_submitted>May 27, 2020</last_update_submitted>
  <last_update_submitted_qc>May 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 29, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Minimal invasive</keyword>
  <keyword>Biopsy</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/NCT02975128
org study id: NL58040.091.16
nct id: NCT02975128
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study will assess whether it is feasible to remove small breast cancers completely using
      the Breast Lesion Excision System under Ultrasound guidance.
Rationale: In the Netherlands, ≥7000 women are operated for small breast cancers yearly. In
      this study, we will evaluate under which conditions it is possible to excise small breast
      cancers using the Breast Lesion Excision System (BLES) under ultrasound (US) guidance. When
      successful, this will allow ambulatory treatment of women with small breast cancers,
      improving the cosmetic outcome and quality of life.

      Objective: Our study aim is to assess whether it is feasible to remove small breast cancers
      completely using the BLES system under US guidance.

      Study design: This is a multi-centre, translational clinical phase II study in 125 women with
      cancers ≤1.5 cm based upon US measurements, and without mammographic evidence of more
      extensive disease (e.g. microcalcifications).

      Study population: Women with cancers ≤1.5 cm based upon US measurements, if there is no
      mammographic evidence of more extensive disease (e.g. microcalcifications or extensive
      architectural distortion), and the tumor lies ≥6 mm away from the dermis, nipple or pectoral
      muscle, are eligible for this study.

      Intervention: In 125 women with cancers ≤1.5 cm based upon US measurements, and without
      mammographic evidence of more extensive disease (e.g. microcalcifications), we will conduct
      additional preoperative breast MRI to ascertain lesion size, after informed consent has been
      obtained. If the lesion is confirmed ≤1.5 cm on MRI and lying ≥6 mm away from the dermis,
      nipple and pectoral muscle, the patient is eligible. Moreover, patients will be asked to fill
      out the questionnaire, detailing their risk profile and comorbidity index.

      Under general anaesthesia for the normal surgical procedure, the tumor is first removed using
      the BLES system under US guidance, through a small skin incision (<1 cm). Next, the normal
      surgical procedure is performed, excising the BLES excision cavity and a ≥ 1cm margin of
      surrounding tissue, also guided by the US appearance after the BLES procedure. Margin
      assessment will be performed separately for the BLES excision and the surgical specimen of
      the surrounding tissue.

      Main study parameters/endpoints: Main endpoint of the study is the frequency of successful
      complete tumor excision by the BLES system, where successful is defined as 'having tumor free
      margins, and no residual (in situ) cancer in the surgical specimen'.

      Nature and extent of the burden and risks associated with participation, benefit and group
      relatedness: Our approach allows to test the feasibility of this highly innovating approach
      to remove breast cancer, with minimal negative effects or possible complications.

      While there is no direct benefit nor detrimental effect from this study to the patients
      participating, the study has large implications for many women, as breast cancer remains the
      most common cancer in women, and due to screening, most cancers are small. Further reduction
      of the impact of local treatment is still desired as the psychosocial and somatic effects of
      breast deformation can be substantial.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Frequency of successful complete tumor excision by the BLES system.
time frame: Through study completion, an average of two months
description: Successful is defined as 'having tumor free margins, and no residual (in situ) cancer in the surgical specimen'.
measure: Quality of the margin evaluation of the biopsy specimen and the eventual surgical specimen.
time frame: Through study completion, an average of two months
measure: In biopsy specimen in which the margin is not completely tumor free, but the Dutch criterion for successful surgery is met (no more than focal (4 mm) margin involvement), we will specifically analyse the residual tumor burden in the surgical excision.
time frame: Through study completion, an average of two months
measure: Assess in retrospect whether we can predict successful tumor extraction based upon other factors than tumor size alone.
time frame: 2 years
description: Parameters categorized in:
Patient related variables obtained from a questionnaire
Lesion related variables
Imaging features
Surgical features
Histopathological and molecular features from the core biopsy
arm group label: Patients
arm group type: Experimental
intervention type: Device
intervention name: BLES system and conventional lumpectomy
description: Each patient undergoes the same procedure. Under general anaesthesia for the normal surgical procedure, the tumor is first removed using the BLES system under US guidance. Next, the normal surgical procedure is performed, excising the BLES excision cavity and a ≥ 1cm margin of surrounding tissue, also guided by the US appearance after the BLES procedure.
arm group label: Patients
criteria: 
gender: Female
minimum age: 19 Years
maximum age: N/A
healthy volunteers: No
last name: Ritse Mann, MD, PhD
role: Principal Investigator
affiliation: Radboud University Medical Center
facility: 
facility: 
country: Netherlands
citation: Allen SD, Nerurkar A, Della Rovere GU. The breast lesion excision system (BLES): a novel technique in the diagnostic and therapeutic management of small indeterminate breast lesions? Eur Radiol. 2011 May;21(5):919-24. doi: 10.1007/s00330-010-2000-7. Epub 2011 Jan 15.
PMID: 21240608
citation: Sie A, Bryan DC, Gaines V, Killebrew LK, Kim CH, Morrison CC, Poller WR, Romilly AP, Schilling K, Sung JH. Multicenter evaluation of the breast lesion excision system, a percutaneous, vacuum-assisted, intact-specimen breast biopsy device. Cancer. 2006 Sep 1;107(5):945-9. doi: 10.1002/cncr.22090.
PMID: 16874817
citation: Medjhoul A, Canale S, Mathieu MC, Uzan C, Garbay JR, Dromain C, Balleyguier C. Breast lesion excision sample (BLES biopsy) combining stereotactic biopsy and radiofrequency: is it a safe and accurate procedure in case of BIRADS 4 and 5 breast lesions? Breast J. 2013 Nov-Dec;19(6):590-4. doi: 10.1111/tbj.12184. Epub 2013 Sep 19.
PMID: 24102869
citation: Allen SD, Osin P, Nerurkar A. The radiological excision of high risk and malignant lesions using the INTACT breast lesion excision system. A case series with an imaging follow up of at least 5 years. Eur J Surg Oncol. 2014 Jul;40(7):824-9. doi: 10.1016/j.ejso.2014.03.022. Epub 2014 Apr 2.
PMID: 24742589
responsible party type: Sponsor
mesh term: Breast Neoplasms