<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/NCT03750396</url>
  </required_header>
  <id_info>
    <org_study_id>CLEAR</org_study_id>
    <nct_id>NCT03750396</nct_id>
  </id_info>
  <brief_title>Local Treatment in ER-positive/HER2-negative Oligo-metastatic Breast Cancer</brief_title>
  <acronym>CLEAR</acronym>
  <official_title>Local Treatment in Addition to Endocrine Therapy in ER-positive/HER2-negative Oligo-metastatic Breast Cancer (CLEAR): a Multicentre, Single -Arm, Phase 2 Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gangnam Severance Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Severance Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Samsung Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Asan Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Gangnam Severance Hospital</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>
      Local treatment in addition to endocrine treatment as 1st line for oligo-metastatic&#xD;
      ER-positive/HER2-negative breast cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Local treatment included surgical resection, stereotactic body radiotherapy, palliative&#xD;
      radiotherapy, and radiofrequency ablation. Stereotactic body radiotherapy is preferred as a&#xD;
      radiation modality.&#xD;
&#xD;
      Endocrine therapies with/without target therapy including CDK4/6 inhibitors or mTOR&#xD;
      inhibitors are the mainstay of 1st line treatment for ER-positive/HER2-negative metastatic&#xD;
      breast cancer.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 1, 2018</start_date>
  <completion_date type="Anticipated">July 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">July 31, 2021</primary_completion_date>
  <phase>Phase 2</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>
    <intervention_model_description>Endocrine therapy is a standard-of-care for 1st line treatment in the patients with ER+/HER2- metastatic breast cancer.&#xD;
Local treatments for metastatic lesions will be added in this group.&#xD;
All patients will undergo local treatments in addition to endocrine therapies.&#xD;
Local treatments include modalities described below:&#xD;
i) Surgical resection: the achievement of tumor-free margin is not obligatory.&#xD;
ii) Stereotactic body radiotherapy&#xD;
iii) Radiofrequency ablation</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>From the date of registration to the date of first PFS failure or last follow-up; assessed up to 6 years; Median PFS of all registered patients will be over 30 months</time_frame>
    <description>Failure: progression or death due to any cause</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>From the date of registration to the date of death or last follow-up; assessed up to 10 years</time_frame>
    <description>Failure: death due to any cause</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">110</enrollment>
  <condition>Breast Cancer</condition>
  <condition>Recurrent Breast Cancer</condition>
  <condition>Stereotactic Body Radiotherapy</condition>
  <condition>Estrogen Receptor Positive Tumor</condition>
  <condition>Her2-negative Tumor</condition>
  <condition>Surgery</condition>
  <arm_group>
    <arm_group_label>Endocrine and local treatments</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Endocrine therapy is a standard-of-care for 1st line treatment in the patients with ER+/HER2- metastatic breast cancer.&#xD;
Endocrine options included aromatase inhibitors, aromatase inhibitors with CDK4/6 inhibitors, fulvestrant, fulvestrant with CDK4/6 inhibitors, everolimus with exemestane, tamoxifen. For premenopausal women, agents for ovarian function suppression using GnRH agonists or surgical ovarian ablation including bilateral salpingo-oophorectomy are allowed.&#xD;
Local treatments for metastatic lesions will be added in this group.&#xD;
Local treatments include modalities described below:&#xD;
i) Surgical resection: the achievement of tumor-free margin is not obligatory. ii) Stereotactic body radiotherapy iii) Radiofrequency ablation</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Surgical resection</intervention_name>
    <description>Surgical resection for their metastatic lesions will be performed. Achievement of tumor-free margin is not mandatory.</description>
    <arm_group_label>Endocrine and local treatments</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Stereotactic body radiotherapy</intervention_name>
    <description>Deliver appropriate metastasis directed radiotherapy while minimizing exposure of surrounding normal tissues. Total radiation dose and fractions are various according to metastatic lesions (57~97.5Gy/6~10 Fraction).</description>
    <arm_group_label>Endocrine and local treatments</arm_group_label>
    <other_name>SBRT</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Radiofrequency ablation</intervention_name>
    <description>RFA is a localized thermal treatment technique designed to induce tumor destruction by heating the tumor tissue to temperatures that exceed 60℃. The alternating current of radiofrequency waves passing down from an uninsulated electrode tip into the surrounding tissues generates changes in the direction of ions and creates ionic agitation and frictional heating. This tissue heating then drives extracellular and intracellular water out of the tissue, resulting in tissue destruction by coagulative necrosis.</description>
    <arm_group_label>Endocrine and local treatments</arm_group_label>
    <other_name>RFA</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        -ER-positive/HER2-negative in primary tumor&#xD;
&#xD;
          -  Oligometastases: ≤ 2 lesions in single organ or site (lung, bone, liver, adrenal&#xD;
             glands, distant LNs)&#xD;
&#xD;
          -  Recurrent cancer after completion of primary treatment (RFI≥1year)&#xD;
&#xD;
          -  Metastatic lesions are feasible for resection or radiotherapy (Size≤3cm)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  De Novo metastatic cancer at initial diganosis&#xD;
&#xD;
          -  Recurrence-free inverval &lt; 1 year&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Biologically woman</gender_description>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joon Jeong, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Gangnam Severance Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sung Gwe Ahn, Ph.D.</last_name>
    <phone>82-2-2019-4402</phone>
    <email>asg2004@yuhs.ac</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Joon Jeong, Ph.D.</last_name>
    <phone>82-2-2019-3379</phone>
    <email>gsjjoon@yuhs.ac</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Gangnam Severance Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>135720</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joon Jeong, M.D.,Ph.D.</last_name>
      <phone>82220193370</phone>
      <email>gsjjoon@yuhs.ac</email>
    </contact>
    <contact_backup>
      <last_name>Sung Gwe Ahn, M.D.</last_name>
      <phone>82220193370</phone>
      <email>asg2004@yuhs.ac</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>November 16, 2018</study_first_submitted>
  <study_first_submitted_qc>November 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 23, 2018</study_first_posted>
  <last_update_submitted>February 12, 2019</last_update_submitted>
  <last_update_submitted_qc>February 12, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 15, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Gangnam Severance Hospital</investigator_affiliation>
    <investigator_full_name>Joon Jeong</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Oligometastasis</keyword>
  <keyword>Local treatments</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/NCT03750396
org study id: CLEAR
nct id: NCT03750396
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Local treatment in addition to endocrine treatment as 1st line for oligo-metastatic
      ER-positive/HER2-negative breast cancer.
Local treatment included surgical resection, stereotactic body radiotherapy, palliative
      radiotherapy, and radiofrequency ablation. Stereotactic body radiotherapy is preferred as a
      radiation modality.

      Endocrine therapies with/without target therapy including CDK4/6 inhibitors or mTOR
      inhibitors are the mainstay of 1st line treatment for ER-positive/HER2-negative metastatic
      breast cancer.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Endocrine therapy is a standard-of-care for 1st line treatment in the patients with ER+/HER2- metastatic breast cancer.
Local treatments for metastatic lesions will be added in this group.
All patients will undergo local treatments in addition to endocrine therapies.
Local treatments include modalities described below:
i) Surgical resection: the achievement of tumor-free margin is not obligatory.
ii) Stereotactic body radiotherapy
iii) Radiofrequency ablation
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-free survival
time frame: From the date of registration to the date of first PFS failure or last follow-up; assessed up to 6 years; Median PFS of all registered patients will be over 30 months
description: Failure: progression or death due to any cause
measure: Overall survival
time frame: From the date of registration to the date of death or last follow-up; assessed up to 10 years
description: Failure: death due to any cause
arm group label: Endocrine and local treatments
arm group type: Experimental
description: Endocrine therapy is a standard-of-care for 1st line treatment in the patients with ER+/HER2- metastatic breast cancer.
Endocrine options included aromatase inhibitors, aromatase inhibitors with CDK4/6 inhibitors, fulvestrant, fulvestrant with CDK4/6 inhibitors, everolimus with exemestane, tamoxifen. For premenopausal women, agents for ovarian function suppression using GnRH agonists or surgical ovarian ablation including bilateral salpingo-oophorectomy are allowed.
Local treatments for metastatic lesions will be added in this group.
Local treatments include modalities described below:
i) Surgical resection: the achievement of tumor-free margin is not obligatory. ii) Stereotactic body radiotherapy iii) Radiofrequency ablation
intervention type: Procedure
intervention name: Surgical resection
description: Surgical resection for their metastatic lesions will be performed. Achievement of tumor-free margin is not mandatory.
arm group label: Endocrine and local treatments
intervention type: Radiation
intervention name: Stereotactic body radiotherapy
description: Deliver appropriate metastasis directed radiotherapy while minimizing exposure of surrounding normal tissues. Total radiation dose and fractions are various according to metastatic lesions (57~97.5Gy/6~10 Fraction).
arm group label: Endocrine and local treatments
other name: SBRT
intervention type: Procedure
intervention name: Radiofrequency ablation
description: RFA is a localized thermal treatment technique designed to induce tumor destruction by heating the tumor tissue to temperatures that exceed 60℃. The alternating current of radiofrequency waves passing down from an uninsulated electrode tip into the surrounding tissues generates changes in the direction of ions and creates ionic agitation and frictional heating. This tissue heating then drives extracellular and intracellular water out of the tissue, resulting in tissue destruction by coagulative necrosis.
arm group label: Endocrine and local treatments
other name: RFA
criteria: 
gender: Female
gender based: Yes
gender description: Biologically woman
minimum age: 20 Years
maximum age: 75 Years
healthy volunteers: No
last name: Joon Jeong, Ph.D.
role: Principal Investigator
affiliation: Gangnam Severance Hospital
last name: Sung Gwe Ahn, Ph.D.
phone: 82-2-2019-4402
email: asg2004@yuhs.ac
last name: Joon Jeong, Ph.D.
phone: 82-2-2019-3379
email: gsjjoon@yuhs.ac
facility: 
status: Recruiting
contact: 
contact backup: 
country: Korea, Republic of
responsible party type: Principal Investigator
investigator affiliation: Gangnam Severance Hospital
investigator full name: Joon Jeong
investigator title: Professor
mesh term: Breast Neoplasms