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/NCT06000033</url>
    </required_header>
    <id_info>
      <org_study_id>RC48HR-/HER2LOW</org_study_id>
      <nct_id>NCT06000033</nct_id>
    </id_info>
    <brief_title>Study of Disitamab Vedotin and Anlotinib in Patients With HR-Negative, HER2-Low-Expressing Metastatic Breast Cancer</brief_title>
    <official_title>Combination of Disitamab Vedotin and Anlotinib in the Treatment of HR-Negative, HER2-Low-Expressing Metastatic Breast Cancer: A Single-Arm, Multicenter, Phase II Clinical Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Qilu Hospital of Shandong University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Qilu Hospital of Shandong University</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>
        Disitamab Vedotin (RC48) contains the novel humanized anti-HER2 antibody conjugated to&#xD;
        monomethyl auristatin E (MMAE) via a cleavable linker , which is the first ADC drug that was&#xD;
        independently developed by Rongchang Biology .The aim of this study is to evaluate the&#xD;
        efficacy and safety of RC48 in Combination with Anlotinib for the treatment of metastatic&#xD;
        breast cancer with HR negativity and HER2 low expression.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 10, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2024</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>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Objective response rate (ORR)</measure>
      <time_frame>1year</time_frame>
      <description>The percentage of cases that have achieved complete or partial remission after drug treatment compared to the total evaluable cases.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Progression-Free Survival (PFS)</measure>
      <time_frame>2years</time_frame>
      <description>All adverse events (AEs) in this study will be encoded using MedDRA and classified according to the NCICTCAEv5.0 grading system.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall Survival (OS)</measure>
      <time_frame>2years</time_frame>
      <description>Defined as the time from the beginning of the patient's treatment to death from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease Control Rate (DCR)</measure>
      <time_frame>1year</time_frame>
      <description>The proportion of patients who achieve complete remission (CR), partial remission (PR), or disease stability (SD) during or after treatment</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of Response (DOR)</measure>
      <time_frame>1year</time_frame>
      <description>Defined as the date from which tumor remission was first recorded (evaluated according to the RECIST 1.1 standard) to the date when disease progression was first recorded (evaluated according to the RECIST 1.1 standard) or the date of death from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>AEs</measure>
      <time_frame>2years</time_frame>
      <description>All adverse events (AEs) in this study will be encoded using MedDRA and classified according to the NCICTCAEv5.0 grading system.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">35</enrollment>
    <condition>Breast Cancer</condition>
    <arm_group>
      <arm_group_label>RC48+Anlotinib</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Disitamab Vedotin : 2 mg/kg，ivgtt，d1-14/28day/cycle Anlotinib: 12mg once daily (taken before meals) orally, continuously for 2 weeks followed by a 1-week break. Each cycle consists of 21 days.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Disitamab Vedotin+Anlotinib</intervention_name>
      <description>Disitamab Vedotin:2 mg/kg，ivgtt，d1-14/28day/cycle Anlotinib: 12mg once daily (taken before meals) orally, continuously for 2 weeks followed by a 1-week break. Each cycle consists of 21 days.</description>
      <arm_group_label>RC48+Anlotinib</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  1)At the time of signing the informed consent form, the age is ≥ 18 years old,&#xD;
               regardless of gender;&#xD;
  &#xD;
            -  2)Patients with pathohistologically proven, locally advanced or metastatic breast&#xD;
               cancer have progressed through second-line standard treatment;&#xD;
  &#xD;
            -  3)The immunohistochemical (IHC) test results of archived tissue (within 6 months) or&#xD;
               fresh biopsy lesions were negative for ER and PR, while patients with low HER-2&#xD;
               expression were HR -, HER2IHC1+, or HER2IHC2+and ISH negative;&#xD;
  &#xD;
            -  4)ECOGPS: 0-1 points;&#xD;
  &#xD;
            -  5)Expected survival time&amp;gt;12 weeks;&#xD;
  &#xD;
            -  6)Adequate organ function: bone marrow function: hemoglobin ≥ 9g/dL; Absolute&#xD;
               neutrophil count ≥ 1.5 × 109/L; White blood cell count ≥ 3.0 × 109/L; Platelets ≥ 100&#xD;
               × 109/L; Liver function: serum total bilirubin ≤ 1.5 times the upper limit of normal&#xD;
               value (ULN); Aspartic acid Transaminase (AST) and alanine Transaminase (ALT) ≤ 3.0 ×&#xD;
               ULN (or ≤ 5.0 in the presence of liver metastasis) × ULN) Renal function: blood&#xD;
               creatinine ≤ 1.5 × The creatinine clearance rate (CrCl) calculated by ULN or Cockcroft&#xD;
               Fault formula method is ≥ 60mL/min; Cardiac function: New York Heart Association&#xD;
               (NYHA) grading&amp;lt;3; Left ventricular Ejection fraction ≥ 50%;&#xD;
  &#xD;
            -  7)At least one measurable lesion defined in RECIST version 1.1;&#xD;
  &#xD;
            -  8)Women of childbearing age must have taken reliable contraceptive measures or&#xD;
               conducted a Pregnancy test (serum or urine) within 7 days before enrollment, and the&#xD;
               result is negative, and are willing to use appropriate methods of contraception during&#xD;
               the test and 8 weeks after the last administration of the test drug. For males, it is&#xD;
               necessary to agree to use appropriate methods of contraception or undergo surgical&#xD;
               sterilization during the trial period and 8 weeks after the last administration of the&#xD;
               investigational drug;&#xD;
  &#xD;
            -  9)The subjects voluntarily joined this study and signed an informed consent form, with&#xD;
               good compliance and cooperation in follow-up.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  1)The second-line treatment within 3 months is paclitaxel drug therapy;&#xD;
  &#xD;
            -  2)Received antitumor therapy or radiation therapy for any malignancy within the&#xD;
               previous five years, excluding cured cervical carcinoma in situ, skin basal cell&#xD;
               carcinoma, or squamous cell carcinoma;&#xD;
  &#xD;
            -  3)had a major non-breast cancer related surgery in the 4 weeks prior to enrollment, or&#xD;
               had not fully recovered from such surgery;&#xD;
  &#xD;
            -  4)Previously received ADC drugs, anti-angiogenesis drugs, anti-HER2 and other&#xD;
               treatments;&#xD;
  &#xD;
            -  5)Serious cardiovascular and cerebrovascular disease or discomfort, including but not&#xD;
               limited to the following diseases: - History of confirmed heart failure or systolic&#xD;
               dysfunction (LVEF&lt;50%) - high-risk uncontrolled arrhythmias - angina, acute myocardial&#xD;
               infarction - clinically significant valvular heart disease - poorly controlled&#xD;
               hypertension (systolic blood pressure &gt;180mmHg and/or diastolic blood pressure&#xD;
               &gt;100mmHg)&#xD;
  &#xD;
            -  6)known allergic history of the drug components of this protocol;&#xD;
  &#xD;
            -  7)A history of immunodeficiency, including HIV testing positive, or other acquired or&#xD;
               congenital immunodeficiency diseases, or a history of organ transplantation;&#xD;
  &#xD;
            -  8)symptomatic brain metastases or brain metastases (excluding prophylactic cranial&#xD;
               irradiation) within 4 weeks prior to initiation of treatment; 9) Pregnant and&#xD;
               lactating women, fertile women who tested positive for baseline pregnancy tests, or&#xD;
               patients of childbearing age who were unwilling to take effective contraception&#xD;
               throughout the trial period;&#xD;
  &#xD;
            -  9)Have a serious concomitant condition or other comorbid condition that interferes&#xD;
               with planned treatment, or any other condition in which the investigator deems the&#xD;
               patient unsuitable for participation in the study.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 14, 2023</study_first_submitted>
    <study_first_submitted_qc>August 14, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 14, 2023</last_update_submitted>
    <last_update_submitted_qc>August 14, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>HER2 low expression</keyword>
    <keyword>Breast Cancer</keyword>
    <keyword>RC48</keyword>
    <keyword>Disitamab Vedotin</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Breast 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>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- 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/NCT06000033
  org study id: RC48HR-/HER2LOW
  nct id: NCT06000033
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  Disitamab Vedotin (RC48) contains the novel humanized anti-HER2 antibody conjugated to
        monomethyl auristatin E (MMAE) via a cleavable linker , which is the first ADC drug that was
        independently developed by Rongchang Biology .The aim of this study is to evaluate the
        efficacy and safety of RC48 in Combination with Anlotinib for the treatment of metastatic
        breast cancer with HR negativity and HER2 low expression.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Objective response rate (ORR)
  time frame: 1year
  description: The percentage of cases that have achieved complete or partial remission after drug treatment compared to the total evaluable cases.
  measure: Progression-Free Survival (PFS)
  time frame: 2years
  description: All adverse events (AEs) in this study will be encoded using MedDRA and classified according to the NCICTCAEv5.0 grading system.
  measure: Overall Survival (OS)
  time frame: 2years
  description: Defined as the time from the beginning of the patient's treatment to death from any cause.
  measure: Disease Control Rate (DCR)
  time frame: 1year
  description: The proportion of patients who achieve complete remission (CR), partial remission (PR), or disease stability (SD) during or after treatment
  measure: Duration of Response (DOR)
  time frame: 1year
  description: Defined as the date from which tumor remission was first recorded (evaluated according to the RECIST 1.1 standard) to the date when disease progression was first recorded (evaluated according to the RECIST 1.1 standard) or the date of death from any cause.
  measure: AEs
  time frame: 2years
  description: All adverse events (AEs) in this study will be encoded using MedDRA and classified according to the NCICTCAEv5.0 grading system.
  arm group label: RC48+Anlotinib
  arm group type: Experimental
  description: Disitamab Vedotin : 2 mg/kg，ivgtt，d1-14/28day/cycle Anlotinib: 12mg once daily (taken before meals) orally, continuously for 2 weeks followed by a 1-week break. Each cycle consists of 21 days.
  intervention type: Drug
  intervention name: Disitamab Vedotin+Anlotinib
  description: Disitamab Vedotin:2 mg/kg，ivgtt，d1-14/28day/cycle Anlotinib: 12mg once daily (taken before meals) orally, continuously for 2 weeks followed by a 1-week break. Each cycle consists of 21 days.
  arm group label: RC48+Anlotinib
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  responsible party type: Sponsor
  mesh term: Breast Neoplasms
  mesh term: Disitamab vedotin
  sharing ipd: No