xml: <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/NCT05993559</url>
    </required_header>
    <id_info>
      <org_study_id>3-2023-0178</org_study_id>
      <nct_id>NCT05993559</nct_id>
    </id_info>
    <brief_title>Necessity of Post-mastectomy Radiotherapy After Neoadjuvant Chemotherapy and Mastectomy</brief_title>
    <official_title>Necessity of Post-mastectomy Radiotherapy in Breast Cancer Patients With an Excellent Response After Neoadjuvant Chemotherapy: A Phase 3, Multicenter, Randomized Controlled Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Gangnam Severance Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </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>
        Postoperative radiotherapy is generally recommended for patients with breast cancer who have&#xD;
        undergone breast-conserving surgery, regardless of prior chemotherapy. However, the criteria&#xD;
        for postoperative radiation therapy (PMRT) in patients with breast cancer who have received&#xD;
        upfront chemotherapy and mastectomy remain controversial. PMRT is recommended for patients&#xD;
        with suspected axillary lymph node metastases before chemotherapy or residual cancer in the&#xD;
        axillary lymph nodes after surgery, but this varies by institution and physician. In&#xD;
        particular, breast cancer patients with a very good treatment response (pCR or RCB 0-I after&#xD;
        prior chemotherapy) have a very good prognosis, and the question of whether PMRT is necessary&#xD;
        for these patients continues to be raised. With the addition of new targeted therapies and&#xD;
        immuno-oncology agents to conventional chemotherapy, the number of patients with good&#xD;
        response is increasing, but there are no prospective studies to date.&#xD;
  &#xD;
        The studies that have evaluated the need for PMRT in breast cancer patients with a very good&#xD;
        treatment response after upfront chemotherapy and mastectomy are all retrospective studies,&#xD;
        lacking evidence to apply to standard of care, and have different definitions of a good&#xD;
        treatment response group. Therefore, in this study, the investigators aim to reduce&#xD;
        unnecessary overtreatment by comparing survival between PMRT and no PMRT in breast cancer&#xD;
        patients with a good response to prior chemotherapy and mastectomy, demonstrating&#xD;
        non-inferiority of PMRT to no PMRT. By doing so, the investigators hope to reduce patients'&#xD;
        side effects and discomfort, improve their satisfaction and quality of life, and contribute&#xD;
        to a new standard of care.&#xD;
  &#xD;
        The purpose of this study is to confirm that in patients with breast cancer who have&#xD;
        undergone mastectomy after prior neoadjuvant chemotherapy, omitting radiotherapy is&#xD;
        non-inferior to post-mastectomy radiotherapy (PMRT) in terms of 5-year disease-free survival&#xD;
        (DFS) in patients with pathologic complete remission and a good response to treatment&#xD;
        corresponding to RCB class 0-I, compared to patients treated with PMRT.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 11, 2023</start_date>
    <completion_date type="Anticipated">July 10, 2031</completion_date>
    <primary_completion_date type="Anticipated">April 10, 2031</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>5 year invasive disease free survival (iDFS)</measure>
      <time_frame>5 year</time_frame>
      <description>Invasive disease-free survival is defined as first invasive recurrence (local, regional, or distant), second invasive cancer (contralateral breast or other cancer), or death from any cause from the date of enrollment.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Overall survival</measure>
      <time_frame>5 year</time_frame>
      <description>5-year overall survival (OS): Overall survival is defined as the time from subject enrollment to death from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Locoregional recurrense free survival</measure>
      <time_frame>5 year</time_frame>
      <description>5-year locoregional recurrence-free interval (LRFI): LRFI is defined as the time of first local recurrence of invasive breast cancer from date of enrollment.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Distant metastasis free surviva</measure>
      <time_frame>5 year</time_frame>
      <description>5-year distant metastasis-free survival (DMFS): Distant metastasis-free survival is defined as the time from enrollment to the i) first distant metastasis of breast cancer confirmed by imaging (biopsy is performed at the discretion of the investigator). ii) death from breast cancer. iii) death from unknown or non-breast cancer causes.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Complications of radiotherapy</measure>
      <time_frame>5 year</time_frame>
      <description>Information on radiotherapy complications including but not restricted to the following items will be collected and any examinations can be ordered at the discretion of the investigator if a patient presents symptoms:&#xD;
  Neutropenia&#xD;
  Cardiac disease: pericarditis, sinus tachycardia, angina, pericardial effusion, tamponade, cardiac enlargement, heart failure etc.&#xD;
  Pulmonary disease: dry cough, dyspnea, pneumonitis etc.&#xD;
  Lymphedema of the arm&#xD;
  Skin symptoms: erythema, edema, ulceration, hemorrhage, necrosis etc.&#xD;
  Esophageal disease: dysphagia, odynophagia, obstruction, ulceration, perforation, fistula etc.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">1314</enrollment>
    <condition>Breast Cancer</condition>
    <arm_group>
      <arm_group_label>No PMRT</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>No radiation therapy after neoadjuvant chemotherapy and surgery.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>PMRT</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Arm Description: Proceed with postoperative radiotherapy, following the guidelines of the respective institution, but advising patients to apply the following points whenever possible.&#xD;
  If radiation therapy is administered, include the chest wall and regional LNs.&#xD;
  If PMRT field to regional LN, include Axillary LN level III, level IV, Internal mammary LN (1-3rd ICS).</description>
    </arm_group>
    <intervention>
      <intervention_type>Radiation</intervention_type>
      <intervention_name>Arm I (No PMRT)</intervention_name>
      <description>The purpose of this study is to confirm that in patients with breast cancer who have undergone mastectomy after prior neoadjuvant chemotherapy, omitting radiotherapy is non-inferior to post-mastectomy radiotherapy (PMRT) in terms of 5-year disease-free survival (DFS) in patients with pathologic complete remission and a good response to treatment corresponding to RCB class 0-I, compared to patients treated with PMRT.</description>
      <arm_group_label>No PMRT</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Radiation</intervention_type>
      <intervention_name>Arm II (PMRT)</intervention_name>
      <description>The purpose of this study is to confirm that in patients with breast cancer who have undergone mastectomy after prior neoadjuvant chemotherapy, omitting radiotherapy is non-inferior to post-mastectomy radiotherapy (PMRT) in terms of 5-year disease-free survival (DFS) in patients with pathologic complete remission and a good response to treatment corresponding to RCB class 0-I, compared to patients treated with PMRT.</description>
      <arm_group_label>PMRT</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Patients 20 years of age or older with histologically confirmed invasive breast&#xD;
               cancer.&#xD;
  &#xD;
            2. Patients with clinical stage IIB-III at the time of diagnosis (including cases of&#xD;
               cT1N1 with multiple masses observed during clinical stage IIA). Patients are&#xD;
               considered node positive if they have either suspected lymph node metastasis on&#xD;
               imaging studies (U/S, breast MRI, PET-CT) or confirmed by pathology.&#xD;
  &#xD;
            3. Patients who have undergone mastectomy after prior neoadjuvant chemotherapy.&#xD;
  &#xD;
            4. Patients with pathologic complete response (pCR) or residual cancer burden (RCB) class&#xD;
               0-I based on postoperative pathology.&#xD;
  &#xD;
               Complete remission is defined as ypT0/is ypN0. RCB class 0 means complete remission&#xD;
               and RCB class 1 is defined as an RCB score ≥0-1.36 as determined by the pathology&#xD;
               department at the site.&#xD;
  &#xD;
            5. Patients not previously treated for invasive breast cancer.&#xD;
  &#xD;
            6. Patients with a systemic performance status of 0-2 based on ECOG.&#xD;
  &#xD;
            7. Patients who signed the informed consent prior to study entry.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Patients with a prior history of invasive breast cancer (patients with a prior history&#xD;
               of intraepithelial carcinoma of the breast may be enrolled)&#xD;
  &#xD;
            2. Patients with bilateral breast cancer&#xD;
  &#xD;
            3. Patients with a prior diagnosis of cancer other than breast cancer within 5 years&#xD;
               (however, adequately treated skin cancer other than melanoma and thyroid cancer are&#xD;
               eligible for enrollment.)&#xD;
  &#xD;
            4. Patients with pathologically or imaging confirmed systemic metastases&#xD;
  &#xD;
            5. Patients with a history of prior irradiation or isotope therapy to the rib cage and&#xD;
               axillary region contralateral to the breast cancer lesion&#xD;
  &#xD;
            6. Patients with suspected supraclavicular/infraclavicular lymph node metastases and&#xD;
               internal mammary lymph node metastases&#xD;
  &#xD;
            7. Pregnant or lactating patients&#xD;
  &#xD;
            8. Patients who have difficulty understanding the contents of the consent form and&#xD;
               completing the survey.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>20 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 20, 2023</study_first_submitted>
    <study_first_submitted_qc>August 8, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 15, 2023</study_first_posted>
    <last_update_submitted>August 8, 2023</last_update_submitted>
    <last_update_submitted_qc>August 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 15, 2023</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>
    <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>
  
  
text: 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/NCT05993559
  org study id: 3-2023-0178
  nct id: NCT05993559
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Postoperative radiotherapy is generally recommended for patients with breast cancer who have
        undergone breast-conserving surgery, regardless of prior chemotherapy. However, the criteria
        for postoperative radiation therapy (PMRT) in patients with breast cancer who have received
        upfront chemotherapy and mastectomy remain controversial. PMRT is recommended for patients
        with suspected axillary lymph node metastases before chemotherapy or residual cancer in the
        axillary lymph nodes after surgery, but this varies by institution and physician. In
        particular, breast cancer patients with a very good treatment response (pCR or RCB 0-I after
        prior chemotherapy) have a very good prognosis, and the question of whether PMRT is necessary
        for these patients continues to be raised. With the addition of new targeted therapies and
        immuno-oncology agents to conventional chemotherapy, the number of patients with good
        response is increasing, but there are no prospective studies to date.
  
        The studies that have evaluated the need for PMRT in breast cancer patients with a very good
        treatment response after upfront chemotherapy and mastectomy are all retrospective studies,
        lacking evidence to apply to standard of care, and have different definitions of a good
        treatment response group. Therefore, in this study, the investigators aim to reduce
        unnecessary overtreatment by comparing survival between PMRT and no PMRT in breast cancer
        patients with a good response to prior chemotherapy and mastectomy, demonstrating
        non-inferiority of PMRT to no PMRT. By doing so, the investigators hope to reduce patients'
        side effects and discomfort, improve their satisfaction and quality of life, and contribute
        to a new standard of care.
  
        The purpose of this study is to confirm that in patients with breast cancer who have
        undergone mastectomy after prior neoadjuvant chemotherapy, omitting radiotherapy is
        non-inferior to post-mastectomy radiotherapy (PMRT) in terms of 5-year disease-free survival
        (DFS) in patients with pathologic complete remission and a good response to treatment
        corresponding to RCB class 0-I, compared to patients treated with PMRT.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: 5 year invasive disease free survival (iDFS)
  time frame: 5 year
  description: Invasive disease-free survival is defined as first invasive recurrence (local, regional, or distant), second invasive cancer (contralateral breast or other cancer), or death from any cause from the date of enrollment.
  measure: Overall survival
  time frame: 5 year
  description: 5-year overall survival (OS): Overall survival is defined as the time from subject enrollment to death from any cause.
  measure: Locoregional recurrense free survival
  time frame: 5 year
  description: 5-year locoregional recurrence-free interval (LRFI): LRFI is defined as the time of first local recurrence of invasive breast cancer from date of enrollment.
  measure: Distant metastasis free surviva
  time frame: 5 year
  description: 5-year distant metastasis-free survival (DMFS): Distant metastasis-free survival is defined as the time from enrollment to the i) first distant metastasis of breast cancer confirmed by imaging (biopsy is performed at the discretion of the investigator). ii) death from breast cancer. iii) death from unknown or non-breast cancer causes.
  measure: Complications of radiotherapy
  time frame: 5 year
  description: Information on radiotherapy complications including but not restricted to the following items will be collected and any examinations can be ordered at the discretion of the investigator if a patient presents symptoms:
  Neutropenia
  Cardiac disease: pericarditis, sinus tachycardia, angina, pericardial effusion, tamponade, cardiac enlargement, heart failure etc.
  Pulmonary disease: dry cough, dyspnea, pneumonitis etc.
  Lymphedema of the arm
  Skin symptoms: erythema, edema, ulceration, hemorrhage, necrosis etc.
  Esophageal disease: dysphagia, odynophagia, obstruction, ulceration, perforation, fistula etc.
  arm group label: No PMRT
  arm group type: Experimental
  description: No radiation therapy after neoadjuvant chemotherapy and surgery.
  arm group label: PMRT
  arm group type: Placebo Comparator
  description: Arm Description: Proceed with postoperative radiotherapy, following the guidelines of the respective institution, but advising patients to apply the following points whenever possible.
  If radiation therapy is administered, include the chest wall and regional LNs.
  If PMRT field to regional LN, include Axillary LN level III, level IV, Internal mammary LN (1-3rd ICS).
  intervention type: Radiation
  intervention name: Arm I (No PMRT)
  description: The purpose of this study is to confirm that in patients with breast cancer who have undergone mastectomy after prior neoadjuvant chemotherapy, omitting radiotherapy is non-inferior to post-mastectomy radiotherapy (PMRT) in terms of 5-year disease-free survival (DFS) in patients with pathologic complete remission and a good response to treatment corresponding to RCB class 0-I, compared to patients treated with PMRT.
  arm group label: No PMRT
  intervention type: Radiation
  intervention name: Arm II (PMRT)
  description: The purpose of this study is to confirm that in patients with breast cancer who have undergone mastectomy after prior neoadjuvant chemotherapy, omitting radiotherapy is non-inferior to post-mastectomy radiotherapy (PMRT) in terms of 5-year disease-free survival (DFS) in patients with pathologic complete remission and a good response to treatment corresponding to RCB class 0-I, compared to patients treated with PMRT.
  arm group label: PMRT
  criteria: 
  gender: All
  minimum age: 20 Years
  maximum age: N/A
  healthy volunteers: No
  responsible party type: Principal Investigator
  investigator affiliation: Gangnam Severance Hospital
  investigator full name: Joon Jeong
  investigator title: Professor
  mesh term: Breast Neoplasms