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/NCT06015113</url>
    </required_header>
    <id_info>
      <org_study_id>ECCO-KY-22004</org_study_id>
      <nct_id>NCT06015113</nct_id>
    </id_info>
    <brief_title>Efficacy and Safety of Disitamab Vedotin Plus Pyrotinib or Naratinib in HER2-positive Breast Cancer Patients With Brain Metastasis</brief_title>
    <official_title>Efficacy and Safety of Disitamab Vedotin Plus Pyrotinib or Naratinib in HER2-positive Breast Cancer Patients With Brain Metastasis</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Xi'an International Medical Center Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Xi'an International Medical Center Hospital</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Basis: Brain metastasis is very common in breast cancer, and HER2 positivity is a risk factor&#xD;
        for high incidence of brain metastasis, with approximately 50% of HER2+ MBC cases&#xD;
        experiencing brain metastasis. The reason for this is that as the efficacy of HER2-targeted&#xD;
        therapy improves, the survival of these patients significantly extends, leading to an&#xD;
        increase in the occurrence rate of brain metastasis events in the late stage of MBC. In the&#xD;
        systemic treatment of HER2+ breast cancer brain metastasis, various HER2-targeted drugs have&#xD;
        been explored, but none have achieved satisfactory therapeutic effects. Therefore, it is&#xD;
        imperative to explore new treatment options. ADC drugs have shown some efficacy in brain&#xD;
        metastasis patients, and as a domestically developed ADC drug, trastuzumab vedotin has&#xD;
        demonstrated good anti-tumor effects. The treatment model combining trastuzumab vedotin with&#xD;
        small molecule TKIs has been rarely reported, so we are attempting to use the treatment model&#xD;
        of trastuzumab vedotin combined with pyrotinib or neratinib to explore its efficacy and&#xD;
        safety in patients with HER2-positive brain metastasis.&#xD;
  &#xD;
        Method: The plan is to recruit HER2-positive breast cancer patients with brain metastasis and&#xD;
        use the treatment of trastuzumab vedotin combined with pyrotinib or neratinib (specific&#xD;
        treatment drugs to be selected during the study).&#xD;
  &#xD;
        Procedure: All subjects will undergo screening, treatment, and follow-up periods, strictly&#xD;
        adhering to relevant GCP regulations during the treatment process.&#xD;
  &#xD;
        Expectations: Through this study, preliminary efficacy and safety data of trastuzumab vedotin&#xD;
        combined with pyrotinib or neratinib treatment will be provided for patients with HER2+ brain&#xD;
        metastatic BC.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Treatment Plan After patient screening, patients will receive treatment with trastuzumab&#xD;
        injection plus either pyrotinib maleate tablets or neratinib maleate tablets, with each cycle&#xD;
        lasting 14 days until disease progression. Trastuzumab Injection: Intravenous infusion,&#xD;
        initial loading dose of 2 mg/kg, administered via intravenous infusion over 30-90 minutes&#xD;
        (usually recommended around 60 minutes), administered on day 1 of each cycle, with each cycle&#xD;
        lasting 14 days. Pyrotinib Maleate Tablets: 400 mg, taken orally once daily, within 30&#xD;
        minutes after a meal, at the same time every day. Taken continuously, with each cycle lasting&#xD;
        14 days. If a patient misses a dose of pyrotinib, it should not be made up for, and the next&#xD;
        dose should be taken as scheduled. Neratinib Maleate Tablets: 240 mg, taken orally once daily&#xD;
        with a meal, at the same time every day. The neratinib tablet should be swallowed whole (it&#xD;
        should not be chewed, crushed, or split before swallowing). Taken continuously, with each&#xD;
        cycle lasting 14 days. If a patient misses a dose of neratinib, it should not be made up for,&#xD;
        and the next dose should be taken as scheduled. Note: The choice between pyrotinib maleate&#xD;
        tablets or neratinib maleate tablets for treatment should be based on the patient's previous&#xD;
        treatment history as decided by the investigator. Treatment medication should be continued&#xD;
        until disease progression or the occurrence of intolerable toxic reactions.&#xD;
  &#xD;
        Study Steps 1) Screening Period (Visit 1: -14 to -1 days, approximately 2 weeks): Subjects&#xD;
        will sign an informed consent form during Visit 1 and undergo a series of examinations (see&#xD;
        Table 1. Treatment Flowchart). Based on the examination results and inclusion/exclusion&#xD;
        criteria, the investigator will determine if the subject meets the inclusion criteria and&#xD;
        does not meet the exclusion criteria. 2) Treatment Period (Visit 2 to disease progression, 1&#xD;
        visit every 2 cycles): Subjects will receive treatment with trastuzumab injection plus&#xD;
        pyrotinib maleate tablets plus capecitabine tablets on the experimental Day 0, with each&#xD;
        cycle lasting 21 days, until disease progression. During this period, a series of&#xD;
        examinations will be conducted every 2 cycles (see flowchart for visits 2 to N). The&#xD;
        investigator will evaluate the effectiveness and safety of the treatment based on the&#xD;
        subject's examination results. 3) Survival Follow-up Period (1 follow-up every 3 months after&#xD;
        withdrawal from the study): After patients withdraw due to disease progression or other&#xD;
        endpoint events, a telephone follow-up will be conducted every 3 months until the patient's&#xD;
        death or loss to follow-up. Detailed records of disease progression, related treatments, and&#xD;
        survival information should be documented.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">April 2027</completion_date>
    <primary_completion_date type="Anticipated">April 2026</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>Progression-free survival</measure>
      <time_frame>The time from randomization to the first documented tumor progression or death from any cause, whichever came first, assessed up to 100 months</time_frame>
      <description>It is an indicator of the long-term efficacy of the drug.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Objective Response Rate</measure>
      <time_frame>4 weeks</time_frame>
      <description>The proportion of patients with the best response of complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease Control Rate</measure>
      <time_frame>4 weeks</time_frame>
      <description>The proportion of patients with tumor shrinkage or stability maintained for a certain period, including cases of CR, PR, and stable disease (SD)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival</measure>
      <time_frame>the time from randomization to death from any cause，whichever came first, assessed up to 100 months.</time_frame>
      <description>It is an indicator of the long-term efficacy of the drug.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">20</enrollment>
    <condition>Breast Cancer</condition>
    <arm_group>
      <arm_group_label>Label 1</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>tale Disitamab Vedotin with pyrotinib or neratinib</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Disitamab Vedotin plus pyrotinib or naratinib</intervention_name>
      <description>Trastuzumab Injection: Intravenous infusion, initial loading dose of 2 mg/kg, administered via intravenous infusion over 30-90 minutes (usually recommended around 60 minutes), administered on day 1 of each cycle, with each cycle lasting 14 days.&#xD;
  Pyrotinib Maleate Tablets: 400 mg, taken orally once daily, within 30 minutes after a meal, at the same time every day. Taken continuously, with each cycle lasting 14 days.&#xD;
  Neratinib Maleate Tablets: 240 mg, taken orally once daily with a meal, at the same time every day. The neratinib tablet should be swallowed whole (it should not be chewed, crushed, or split before swallowing). Taken continuously, with each cycle lasting 14 days.</description>
      <arm_group_label>Label 1</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patients who can voluntarily sign an informed consent form;&#xD;
  &#xD;
            -  Females aged ≥18 years old when signing the informed consent form;&#xD;
  &#xD;
            -  ECOG PS physical status score of 0 to 2 points;&#xD;
  &#xD;
            -  Histologically confirmed HER2-positive metastatic breast cancer patients; Note: HER2&#xD;
               positivity refers to at least one occurrence of tumor cell immunohistochemical&#xD;
               staining intensity of 3+ or confirmed as positive by fluorescence in situ&#xD;
               hybridization [FISH] in the pathological testing/re-review of the primary or&#xD;
               metastatic lesions conducted by the participating center's pathology department;&#xD;
  &#xD;
            -  Brain metastases confirmed by MRI/enhanced CT, with at least one measurable lesion in&#xD;
               the brain based on RECIST 1.1 criteria;&#xD;
  &#xD;
            -  Expected survival period ≥3 months;&#xD;
  &#xD;
            -  Patient types: Cohort A - newly diagnosed brain metastases patients; Cohort B -&#xD;
               patients with progression after whole-brain radiotherapy or stereotactic radiosurgery;&#xD;
  &#xD;
            -  Left ventricular ejection fraction (LVEF) ≥50%;&#xD;
  &#xD;
            -  QT interval corrected by Fridericia formula (QTcF) of 12-lead electrocardiogram:&#xD;
               &lt;450ms for males, &lt;470ms for females;&#xD;
  &#xD;
            -  The following conditions should be met in the blood routine examination:① Absolute&#xD;
               neutrophil count (ANC) ≥1.5×10^9/L, ② Platelet count ≥100×10^9/L, ③ Hemoglobin ≥90g/L,&#xD;
               ④ White blood cell count ≥3.0×10^9/L;&#xD;
  &#xD;
            -  Liver function meets the following conditions: ① Serum total bilirubin ≤1.5×upper&#xD;
               limit of normal (ULN), or ≤3×ULN if there are liver metastases, ② Aspartate&#xD;
               aminotransferase (AST) or alanine aminotransferase (ALT) ≤3×ULN, or ≤5×ULN if there&#xD;
               are liver metastases;&#xD;
  &#xD;
            -  Renal function meets the following conditions: Serum creatinine ≤1.5×ULN or creatinine&#xD;
               clearance ≥50mL/min (calculated according to the Cockroft-Gault formula);&#xD;
  &#xD;
            -  Female patients who meet the following conditions can participate in this study: ①&#xD;
               Infertility; ② Capable of fertility, with a negative blood pregnancy test result&#xD;
               within 7 days before the first administration of the investigational drug, not&#xD;
               breastfeeding, and adopting effective contraceptive measures during the screening&#xD;
               period, throughout the study, and within 6 months after the last administration of the&#xD;
               study drug.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patients who have received treatment with anti-HER2 ADC drugs;&#xD;
  &#xD;
            -  Patients who have received sequential treatment with pyrotinib and neratinib;&#xD;
  &#xD;
            -  Patients with extensive leptomeningeal metastases and poor response to steroid&#xD;
               dehydration therapy for brain metastases;&#xD;
  &#xD;
            -  Presence of third space fluid accumulation (such as significant pleural effusion or&#xD;
               ascites) that cannot be controlled by drainage or other methods;&#xD;
  &#xD;
            -  Patients who have received chemotherapy, major surgery, or molecular targeted therapy&#xD;
               within 2 weeks prior to enrollment; patients who have received endocrine therapy&#xD;
               within 1 week prior to enrollment; patients who have received nitrosoureas or&#xD;
               mitomycin chemotherapy within 6 weeks prior to enrollment;&#xD;
  &#xD;
            -  Concurrent use of any other anticancer treatment;&#xD;
  &#xD;
            -  History of or current concurrent malignancies within the past 5 years, excluding cured&#xD;
               cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder&#xD;
               carcinoma [Ta (non-invasive tumor), Tis (carcinoma in situ), and T1 (tumor invading&#xD;
               the lamina propria)];&#xD;
  &#xD;
            -  Underwent major surgery (including thoracotomy biopsy), experienced significant trauma&#xD;
               (such as fractures), had unhealed wounds or fractures at the time of screening, or&#xD;
               anticipated the need for major surgery during the study treatment period, within the 4&#xD;
               weeks prior to randomization;&#xD;
  &#xD;
            -  History of myocardial infarction within the past 6 months; history of New York Heart&#xD;
               Association (NYHA) class ≥II congestive heart failure that is not controlled by&#xD;
               medication, severe arrhythmias that cannot be controlled (excluding atrial&#xD;
               fibrillation and paroxysmal supraventricular tachycardia); known decrease in LVEF to&#xD;
               below 50% during or after previous treatment with trastuzumab;&#xD;
  &#xD;
            -  Known allergy to the drugs and excipients involved in this trial;&#xD;
  &#xD;
            -  Known history of hypersensitivity reactions to any investigational drugs;&#xD;
  &#xD;
            -  Subjects deemed unsuitable for participation by other investigators.&#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>Yan Xue</last_name>
      <role>Principal Investigator</role>
      <affiliation>Xi'an International Medical Center Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Yan Xue</last_name>
      <phone>0086-13992830596</phone>
      <email>1410605462@qq.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Xi'an International Medical Center Hospital</name>
        <address>
          <city>Xi'an</city>
          <state>Shaanxi</state>
          <zip>710100</zip>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Yan Xue</last_name>
        <phone>0086-13992830596</phone>
        <email>1410605462@qq.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 8, 2023</study_first_submitted>
    <study_first_submitted_qc>August 27, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 29, 2023</study_first_posted>
    <last_update_submitted>August 27, 2023</last_update_submitted>
    <last_update_submitted_qc>August 27, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 29, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Xi'an International Medical Center Hospital</investigator_affiliation>
      <investigator_full_name>Yan Xue</investigator_full_name>
      <investigator_title>Director of tumor hospital</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Breast Neoplasms</mesh_term>
      <mesh_term>Brain Neoplasms</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Disitamab vedotin</mesh_term>
    </intervention_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/NCT06015113
  org study id: ECCO-KY-22004
  nct id: NCT06015113
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  Basis: Brain metastasis is very common in breast cancer, and HER2 positivity is a risk factor
        for high incidence of brain metastasis, with approximately 50% of HER2+ MBC cases
        experiencing brain metastasis. The reason for this is that as the efficacy of HER2-targeted
        therapy improves, the survival of these patients significantly extends, leading to an
        increase in the occurrence rate of brain metastasis events in the late stage of MBC. In the
        systemic treatment of HER2+ breast cancer brain metastasis, various HER2-targeted drugs have
        been explored, but none have achieved satisfactory therapeutic effects. Therefore, it is
        imperative to explore new treatment options. ADC drugs have shown some efficacy in brain
        metastasis patients, and as a domestically developed ADC drug, trastuzumab vedotin has
        demonstrated good anti-tumor effects. The treatment model combining trastuzumab vedotin with
        small molecule TKIs has been rarely reported, so we are attempting to use the treatment model
        of trastuzumab vedotin combined with pyrotinib or neratinib to explore its efficacy and
        safety in patients with HER2-positive brain metastasis.
  
        Method: The plan is to recruit HER2-positive breast cancer patients with brain metastasis and
        use the treatment of trastuzumab vedotin combined with pyrotinib or neratinib (specific
        treatment drugs to be selected during the study).
  
        Procedure: All subjects will undergo screening, treatment, and follow-up periods, strictly
        adhering to relevant GCP regulations during the treatment process.
  
        Expectations: Through this study, preliminary efficacy and safety data of trastuzumab vedotin
        combined with pyrotinib or neratinib treatment will be provided for patients with HER2+ brain
        metastatic BC.
  Treatment Plan After patient screening, patients will receive treatment with trastuzumab
        injection plus either pyrotinib maleate tablets or neratinib maleate tablets, with each cycle
        lasting 14 days until disease progression. Trastuzumab Injection: Intravenous infusion,
        initial loading dose of 2 mg/kg, administered via intravenous infusion over 30-90 minutes
        (usually recommended around 60 minutes), administered on day 1 of each cycle, with each cycle
        lasting 14 days. Pyrotinib Maleate Tablets: 400 mg, taken orally once daily, within 30
        minutes after a meal, at the same time every day. Taken continuously, with each cycle lasting
        14 days. If a patient misses a dose of pyrotinib, it should not be made up for, and the next
        dose should be taken as scheduled. Neratinib Maleate Tablets: 240 mg, taken orally once daily
        with a meal, at the same time every day. The neratinib tablet should be swallowed whole (it
        should not be chewed, crushed, or split before swallowing). Taken continuously, with each
        cycle lasting 14 days. If a patient misses a dose of neratinib, it should not be made up for,
        and the next dose should be taken as scheduled. Note: The choice between pyrotinib maleate
        tablets or neratinib maleate tablets for treatment should be based on the patient's previous
        treatment history as decided by the investigator. Treatment medication should be continued
        until disease progression or the occurrence of intolerable toxic reactions.
  
        Study Steps 1) Screening Period (Visit 1: -14 to -1 days, approximately 2 weeks): Subjects
        will sign an informed consent form during Visit 1 and undergo a series of examinations (see
        Table 1. Treatment Flowchart). Based on the examination results and inclusion/exclusion
        criteria, the investigator will determine if the subject meets the inclusion criteria and
        does not meet the exclusion criteria. 2) Treatment Period (Visit 2 to disease progression, 1
        visit every 2 cycles): Subjects will receive treatment with trastuzumab injection plus
        pyrotinib maleate tablets plus capecitabine tablets on the experimental Day 0, with each
        cycle lasting 21 days, until disease progression. During this period, a series of
        examinations will be conducted every 2 cycles (see flowchart for visits 2 to N). The
        investigator will evaluate the effectiveness and safety of the treatment based on the
        subject's examination results. 3) Survival Follow-up Period (1 follow-up every 3 months after
        withdrawal from the study): After patients withdraw due to disease progression or other
        endpoint events, a telephone follow-up will be conducted every 3 months until the patient's
        death or loss to follow-up. Detailed records of disease progression, related treatments, and
        survival information should be documented.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Progression-free survival
  time frame: The time from randomization to the first documented tumor progression or death from any cause, whichever came first, assessed up to 100 months
  description: It is an indicator of the long-term efficacy of the drug.
  measure: Objective Response Rate
  time frame: 4 weeks
  description: The proportion of patients with the best response of complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST).
  measure: Disease Control Rate
  time frame: 4 weeks
  description: The proportion of patients with tumor shrinkage or stability maintained for a certain period, including cases of CR, PR, and stable disease (SD)
  measure: Overall survival
  time frame: the time from randomization to death from any cause，whichever came first, assessed up to 100 months.
  description: It is an indicator of the long-term efficacy of the drug.
  arm group label: Label 1
  arm group type: Experimental
  description: tale Disitamab Vedotin with pyrotinib or neratinib
  intervention type: Drug
  intervention name: Disitamab Vedotin plus pyrotinib or naratinib
  description: Trastuzumab Injection: Intravenous infusion, initial loading dose of 2 mg/kg, administered via intravenous infusion over 30-90 minutes (usually recommended around 60 minutes), administered on day 1 of each cycle, with each cycle lasting 14 days.
  Pyrotinib Maleate Tablets: 400 mg, taken orally once daily, within 30 minutes after a meal, at the same time every day. Taken continuously, with each cycle lasting 14 days.
  Neratinib Maleate Tablets: 240 mg, taken orally once daily with a meal, at the same time every day. The neratinib tablet should be swallowed whole (it should not be chewed, crushed, or split before swallowing). Taken continuously, with each cycle lasting 14 days.
  arm group label: Label 1
  criteria: 
  gender: Female
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Yan Xue
  role: Principal Investigator
  affiliation: Xi'an International Medical Center Hospital
  last name: Yan Xue
  phone: 0086-13992830596
  email: 1410605462@qq.com
  facility: 
  contact: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Xi'an International Medical Center Hospital
  investigator full name: Yan Xue
  investigator title: Director of tumor hospital
  mesh term: Breast Neoplasms
  mesh term: Brain Neoplasms
  mesh term: Disitamab vedotin