<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/NCT04481932</url>
  </required_header>
  <id_info>
    <org_study_id>OBU-BC-II-024</org_study_id>
    <nct_id>NCT04481932</nct_id>
  </id_info>
  <brief_title>Trastuzumab Combined With Pyrrolidine and Chemotherapy for Locally HER2 Positive Breast Cancer</brief_title>
  <official_title>Trastuzumab Combined With Pyrotinib and Chemotherapy for Locally Advanced, Inflammatory, or Early HER2-positive Mammary glandsCancer: One Arm, Open, Phase II Clinical Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peking University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Peking 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>
      This study is a one-arm, open, phase II clinical study, and the study subjects are locally&#xD;
      advanced and inflammatoryPatients with sexual or early HER2-positive breast cancer entered&#xD;
      the trial period after signing informed consentTo evaluate trastuzumab combined with&#xD;
      pyrrolitinib and chemotherapy regimen (TCbH+Py) for HER2 positive breastPathologic complete&#xD;
      response rate (pCR) for adenocarcinoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a single-arm, open, phase II clinical study. The subjects are patients with&#xD;
      locally advanced, inflammatory, or early HER2-positive breast cancer. The patients enter the&#xD;
      trial period after signing informed consent. This study aims to evaluate trastuzumab The&#xD;
      pathological complete response rate (pCR) of anti-combined pyrrotinib and chemotherapy&#xD;
      (TCbH+Py) in the treatment of HER2-positive breast cancer.&#xD;
&#xD;
      The subjects began to take continuous medication after joining the group, and the total&#xD;
      duration of medication was 6 cycles. Three to four weeks after the end of treatment, the&#xD;
      surgeon will choose radical mastectomy, modified radical mastectomy or breast-sparing surgery&#xD;
      according to the individual conditions of the patient. Regardless of whether the pCR is&#xD;
      achieved, the adjuvant trastuzumab therapy or trastuzumab plus pertuzumab therapy is&#xD;
      continued after the operation, and the total course of anti-HER2 therapy is up to 1 year&#xD;
      (about 18 treatment cycles). According to the clinical stage and molecular classification of&#xD;
      the tumor, it is necessary to decide whether adjuvant radiotherapy, chemotherapy and&#xD;
      endocrine therapy are needed.&#xD;
&#xD;
      After the subject finishes all treatments, the subjects who are out of the group for non-PD&#xD;
      and non-death causes need to receive the validity Follow-up until PD, start receiving other&#xD;
      anti-tumor drug treatment or death (whichever comes first).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Anticipated">July 2020</start_date>
  <completion_date type="Anticipated">December 2026</completion_date>
  <primary_completion_date type="Anticipated">June 2022</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>pathological complete response (pCR)</measure>
    <time_frame>From enrollment to 18 weeks</time_frame>
    <description>Breast without invasive carcinoma and carcinoma in situ or only carcinoma in situ (ypT0 or ypT0/is)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>overall survival (OS)</measure>
    <time_frame>At least two years</time_frame>
    <description>From the date of enrollment to the time of death due to any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety index</measure>
    <time_frame>At least two years</time_frame>
    <description>ECOG PS score, vital signs, physical examination, laboratory examination indicators, ECG, echocardiography, adverse events (AE) according to NCI-CTC AE 5.0 standard</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">104</enrollment>
  <condition>HER2-positive Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Trastuzumab combined with Pyrotinib and chemotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The dosage of the above drugs can be adjusted according to the adverse reactions of the subjects. The subject continued to use the drug until the full cycle or the disease progressed or the toxicity was intolerable or withdrawn, or the researcher judged that the medication must be terminated.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trastuzumab combined with Pyrotinib and chemotherapy</intervention_name>
    <description>Pyrotinib is a small molecule, irreversible tyrosine kinase inhibitor with targets of epidermal growth factor receptor 1 (EGFR/HER1/ErbB1), human epidermal factor receptor 2 (HER2/ErbB2/Neu) and human epidermis Factor Receptor 4 (HER4/ErbB4).&#xD;
As a new generation of anti-HER2 therapeutic targeted drugs, pirotinib covalently binds to the ATP binding sites of the kinase regions of EGFR, HER2 and HER4 in cells to prevent homogeneity and heterogeneity of EGFR, HER2 and HER4 in tumor cells Dimer formation, inhibiting its own phosphorylation, blocking the activation of downstream signaling pathways, thereby inhibiting tumor cell growth</description>
    <arm_group_label>Trastuzumab combined with Pyrotinib and chemotherapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Female between 18 and 70 years old;&#xD;
&#xD;
          2. Histologically confirmed as invasive breast cancer;&#xD;
&#xD;
          3. ECOG PS 0-1;&#xD;
&#xD;
          4. The expected survival time is not less than 12 weeks;&#xD;
&#xD;
          5. Standard immunohistochemical HER2-positive breast cancer patients (IHC +++ or FISH&#xD;
             amplification);&#xD;
&#xD;
          6. The status of hormone receptors (ER and PR) can be known.&#xD;
&#xD;
          7. Clinical examination or imaging examination of primary lesion &gt;2cm;&#xD;
&#xD;
          8. Patients who are operable (T2-3, N0-1, M0), locally advanced (T2-3,N2-3, M0 or T4A-C,&#xD;
             any N, M0) or inflammatory breast cancer (T4d, any N, M0) and who have not received&#xD;
             any previous anti-tumor therapy (including radiotherapy, chemotherapy, targeted&#xD;
             therapy, except those who have received bisphosphonate therapy previously);&#xD;
&#xD;
          9. Echocardiography indicated left ventricular ejection fraction (LVEF)≥55%;&#xD;
&#xD;
         10. Adequate organ and bone marrow function, as defined below: a. Neutrophil count (ANC)≥&#xD;
             1,500/mm3 (1.5 × 109/L); B. Platelet count (PLT)≥ 100,000/mm3(100 × 109/L); C.&#xD;
             Hemoglobin (Hb)≥ 9 g/dL(90 g/L); D. Serum creatinine ≤ 1.5 times upper limit of normal&#xD;
             value (ULN) or creatinine clearance ≥ 60 ml/min(based on Cockroft - Gault formula); E.&#xD;
             Total bilirubin (BIL)≤ 1.5 times the upper limit of normal value (ULN); F. AST/SGOT or&#xD;
             ALT/SGPT ≤ 2.5 times upper limit of normal value (ULN);G. Urinary protein &lt;2+; If&#xD;
             urinary protein ≥2+, 24-hour urinary protein quantification shows protein must1 g or&#xD;
             less;&#xD;
&#xD;
         11. I have agreed and signed the informed consent, and am willing and able to comply with&#xD;
             the planned visit, research treatment, laboratory examination and other test&#xD;
             procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Have received any previous anti-tumor treatment for primary invasive breast cancer;&#xD;
&#xD;
          2. Previous (&lt;10 years) or other malignant tumors, except for curable cancer species: a.&#xD;
             basal cell carcinoma of skin and squamous cell carcinoma b. Carcinoma in situ of&#xD;
             cervix&#xD;
&#xD;
          3. For patients with other malignancies, they can also be included in the study if the&#xD;
             time from diagnosis to enrollment exceeds 10 years; Prior surgical treatment is&#xD;
             permitted except for radiotherapy or systemic therapy (chemotherapy or endocrine&#xD;
             therapy);&#xD;
&#xD;
          4. Metastatic breast cancer (M1), bilateral or ipsilateral multifocal breast cancer;&#xD;
&#xD;
          5. Uncontrolled hypertension, systolic blood pressure &gt; 150 MMHG and/or diastolic blood&#xD;
             pressure &gt; 100 MMHG), or clinical symptomatic cardiovascular disease, myocardial&#xD;
             ischemia and myocardial infarction, severe/unstable angina, poor control of cardiac&#xD;
             arrhythmias (including women according to Bazett formula correction QTc interphase &lt;&#xD;
             470 ms), symptoms of congestive heart failure, cerebrovascular accident (including&#xD;
             transient ischemic attack or symptomatic cerebral embolism), NYHA Ⅱ magnitude cardiac&#xD;
             insufficiency;&#xD;
&#xD;
          6. Receive other anti-tumor treatments within 4 weeks before enrollment;&#xD;
&#xD;
          7. Inability to swallow, intestinal obstruction or other factors affecting the use and&#xD;
             absorption of medication;&#xD;
&#xD;
          8. Persons with allergic constitution or known history of allergy to the drug components&#xD;
             of the program;&#xD;
&#xD;
          9. The patient has a severe concomitant disease or other conditions that the researcher&#xD;
             considers inappropriate for the patient to participate in the studyIn any case;&#xD;
&#xD;
         10. Non-surgically sterilized female patients of childbearing age must have negative serum&#xD;
             or urine HCG tests within 14 days prior to study inclusion; And must be non-lactation&#xD;
&#xD;
         11. Other circumstances deemed inappropriate for inclusion by the researcher.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tao Ouyang, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Peking University Cancer Hospital &amp; Institute</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Tao Ouyang, MD</last_name>
    <phone>88271119-5002</phone>
    <email>ouyanghongtao@263.net</email>
  </overall_contact>
  <location>
    <facility>
      <name>Peking University Cancer Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100142</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>TAO OUYANG, M.D</last_name>
      <phone>0086-10-88196696</phone>
      <email>ouyanghongtao@263.net</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 13, 2020</study_first_submitted>
  <study_first_submitted_qc>July 19, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 22, 2020</study_first_posted>
  <last_update_submitted>July 19, 2020</last_update_submitted>
  <last_update_submitted_qc>July 19, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Peking University</investigator_affiliation>
    <investigator_full_name>Tao OUYANG</investigator_full_name>
    <investigator_title>Chairman of Breast Center of Peking University Cancer Hospital</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Trastuzumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04481932
org study id: OBU-BC-II-024
nct id: NCT04481932
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This study is a one-arm, open, phase II clinical study, and the study subjects are locally
      advanced and inflammatoryPatients with sexual or early HER2-positive breast cancer entered
      the trial period after signing informed consentTo evaluate trastuzumab combined with
      pyrrolitinib and chemotherapy regimen (TCbH+Py) for HER2 positive breastPathologic complete
      response rate (pCR) for adenocarcinoma.
This study is a single-arm, open, phase II clinical study. The subjects are patients with
      locally advanced, inflammatory, or early HER2-positive breast cancer. The patients enter the
      trial period after signing informed consent. This study aims to evaluate trastuzumab The
      pathological complete response rate (pCR) of anti-combined pyrrotinib and chemotherapy
      (TCbH+Py) in the treatment of HER2-positive breast cancer.

      The subjects began to take continuous medication after joining the group, and the total
      duration of medication was 6 cycles. Three to four weeks after the end of treatment, the
      surgeon will choose radical mastectomy, modified radical mastectomy or breast-sparing surgery
      according to the individual conditions of the patient. Regardless of whether the pCR is
      achieved, the adjuvant trastuzumab therapy or trastuzumab plus pertuzumab therapy is
      continued after the operation, and the total course of anti-HER2 therapy is up to 1 year
      (about 18 treatment cycles). According to the clinical stage and molecular classification of
      the tumor, it is necessary to decide whether adjuvant radiotherapy, chemotherapy and
      endocrine therapy are needed.

      After the subject finishes all treatments, the subjects who are out of the group for non-PD
      and non-death causes need to receive the validity Follow-up until PD, start receiving other
      anti-tumor drug treatment or death (whichever comes first).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: pathological complete response (pCR)
time frame: From enrollment to 18 weeks
description: Breast without invasive carcinoma and carcinoma in situ or only carcinoma in situ (ypT0 or ypT0/is)
measure: overall survival (OS)
time frame: At least two years
description: From the date of enrollment to the time of death due to any cause
measure: Safety index
time frame: At least two years
description: ECOG PS score, vital signs, physical examination, laboratory examination indicators, ECG, echocardiography, adverse events (AE) according to NCI-CTC AE 5.0 standard
arm group label: Trastuzumab combined with Pyrotinib and chemotherapy
arm group type: Experimental
description: The dosage of the above drugs can be adjusted according to the adverse reactions of the subjects. The subject continued to use the drug until the full cycle or the disease progressed or the toxicity was intolerable or withdrawn, or the researcher judged that the medication must be terminated.
intervention type: Drug
intervention name: Trastuzumab combined with Pyrotinib and chemotherapy
description: Pyrotinib is a small molecule, irreversible tyrosine kinase inhibitor with targets of epidermal growth factor receptor 1 (EGFR/HER1/ErbB1), human epidermal factor receptor 2 (HER2/ErbB2/Neu) and human epidermis Factor Receptor 4 (HER4/ErbB4).
As a new generation of anti-HER2 therapeutic targeted drugs, pirotinib covalently binds to the ATP binding sites of the kinase regions of EGFR, HER2 and HER4 in cells to prevent homogeneity and heterogeneity of EGFR, HER2 and HER4 in tumor cells Dimer formation, inhibiting its own phosphorylation, blocking the activation of downstream signaling pathways, thereby inhibiting tumor cell growth
arm group label: Trastuzumab combined with Pyrotinib and chemotherapy
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Tao Ouyang, MD
role: Study Chair
affiliation: Peking University Cancer Hospital & Institute
last name: Tao Ouyang, MD
phone: 88271119-5002
email: ouyanghongtao@263.net
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Peking University
investigator full name: Tao OUYANG
investigator title: Chairman of Breast Center of Peking University Cancer Hospital
mesh term: Breast Neoplasms
mesh term: Trastuzumab
sharing ipd: No