<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/NCT03243838</url>
  </required_header>
  <id_info>
    <org_study_id>20170328</org_study_id>
    <nct_id>NCT03243838</nct_id>
  </id_info>
  <brief_title>Low-dose Apatinib Combined With Neoadjuvant Chemotherapy in the Treatment of Early Triple Negative Breast Cancer</brief_title>
  <acronym>LANCET</acronym>
  <official_title>Low-dose Apatinib Combined With Neoadjuvant Chemotherapy in the Treatment of Early Triple Negative Breast Cancer (LANCET): A Multicenter, Single-arm, Phase II Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Guangdong Provincial People's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Guangdong Provincial People's 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>
      Triple-negative breast cancer (TNBC) is a special type of breast cancer, endocrine therapy&#xD;
      and targeted therapy are completely ineffective, chemotherapy is currently the only effective&#xD;
      treatment. How to improve postoperative pathologic complete response（pCR）of neoadjuvant&#xD;
      chemotherapy is critical problem to prolong event-free survival (EFS) and overall survival&#xD;
      (OS) of TNBC patients. Apatinib is a new oral small molecule tyrosine protease inhibitor, it&#xD;
      is effective in inhibiting angiogenesis with a very low concentration. So the standard&#xD;
      neoadjuvant chemotherapy regimen of docetaxel and carboplatin combined with apatinib may&#xD;
      improve the postoperative pCR and survival outcomes of TNBC patients. Safety and tolerability&#xD;
      assessed by number of grade 3 and 4 toxicities and hospitalizations.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      All enrolled patients were administered oral apatinib at a dose of 250 mg once daily and&#xD;
      intravenously docetaxel (100 mg/m2) every three weeks for four cycles, followed by epirubicin&#xD;
      (90 mg/m2) plus cyclophosphamide (600 mg/m2) every three weeks for four cycles. All the&#xD;
      treatments were continued until disease progression, patient withdrawal, or unacceptable&#xD;
      toxic effects. Granulocyte colony-stimulating factor (G-CSF) used for prophylaxis of febrile&#xD;
      neutropenia was permitted according to the American Society of Clinical Oncology (ASCO)&#xD;
      guidelines. The biochemical and hematological indexes were evaluated every cycle. Dose&#xD;
      modifications of chemotherapy agents, including dose interruptions and dose reductions, were&#xD;
      permitted due to certain adverse events.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 1, 2018</start_date>
  <completion_date type="Actual">December 31, 2021</completion_date>
  <primary_completion_date type="Actual">October 13, 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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The pathological complete response (pCR) rate in the breast and lymph nodes (ypTis/0ypN0)</measure>
    <time_frame>up to 24 weeks (at the end of cycle 8, each cycle is 21 days)</time_frame>
    <description>Absence of invasive tumor cells in the breast and lymph nodes and was determined by a local pathologist</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>up to 24 weeks (at the end of cycle 8, each cycle is 21 days)</time_frame>
    <description>ORR was assessed according to RECIST version 1.1, which included patients with measurable disease who achieved a complete or partial response of target lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event-free survival (EFS)</measure>
    <time_frame>up to 24 months</time_frame>
    <description>The interval from the start of treatment to progression prior to surgery, post-surgery recurrence, or death due to any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>up to 24 months</time_frame>
    <description>The time from registration to death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>up to 24 weeks</time_frame>
    <description>The treatment-related adverse events were assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI-CTCAE 4.0).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Triple-Negative Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Experimental Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Four cycles of docetaxel combined with apatinib followed by four cycles of epirubicin and cyclophosphamide as Neoadjuvant Treatment for Triple-Negative Breast Cancer</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apatinib</intervention_name>
    <description>All enrolled patients were administered oral apatinib at a dose of 250 mg once daily and intravenously docetaxel (100 mg/m2) every three weeks for four cycles, followed by epirubicin (90 mg/m2) plus cyclophosphamide (600 mg/m2) every three weeks for four cycles. All the treatments were continued until disease progression, patient withdrawal, or unacceptable toxic effects.</description>
    <arm_group_label>Experimental Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically or pathologically confirmed noninflammatory Triple-Negative invasive&#xD;
             breast carcinoma (TNBC). The diagnosis of TNBC was defined below: the estrogen&#xD;
             receptor and progesterone receptor negativity rates were less than 10%, and the human&#xD;
             epidermal growth factor receptor type 2 (HER2) staining was 0 or 1+, and fluorescence&#xD;
             in situ hybridization (FISH) detected no HER2 gene amplification&#xD;
&#xD;
          -  Clinical stage IIA-IIIB&#xD;
&#xD;
          -  Patients must have measurable disease as defined by palpable lesion with caliper&#xD;
             and/or a positive mammogram or ultrasound. Bilateral mammogram and clip placement is&#xD;
             required for study entry. Baseline measurements of the indicator lesions must be&#xD;
             recorded on the Patient Registration Form. To be valid for baseline, the measurements&#xD;
             must have been made within the 14 days if palpable. If not palpable, a mammogram or&#xD;
             MRI must be done within 14 days. If palpable, a mammogram or MRI must be done within 2&#xD;
             months prior to study entry. If clinically indicated, x-rays and scans must be done&#xD;
             within 28 days of study entry.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group(ECOG) performance status 0 to 1 within 14 days of&#xD;
             study entry&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
          -  Adequate organ function within 2 weeks of study entry: Absolute bone marrow function&#xD;
             (hemoglobin concentration of ≥8.0 g/dL, white blood cell count of ≥3000 cells per μL,&#xD;
             absolute neutrophil count of ≥1500 cells per μL, platelet count of ≥70000 cells per&#xD;
             μL), adequate renal function (creatinine was the upper limit of normal or lower), and&#xD;
             adequate liver function (total bilirubin was the upper limit of normal or lower, and&#xD;
             aspartate aminotransferase or alanine aminotransferase was twice the upper limit of&#xD;
             normal or lower)&#xD;
&#xD;
          -  Patients must be aged 18-70 years&#xD;
&#xD;
          -  Women of childbearing potential must have a negative serum pregnancy test performed&#xD;
             within 7 days prior to the start of treatment&#xD;
&#xD;
          -  Women of childbearing potential and men must agree to use adequate contraception&#xD;
             (barrier method of birth control) prior to study entry and for the duration of study&#xD;
             participation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Metastatic disease&#xD;
&#xD;
          -  Prior chemotherapy, hormonal therapy, biologic therapy, investigational agent,&#xD;
             targeted therapy or radiation therapy for current breast cancer. Patients with history&#xD;
             of breast cancer greater than 5 years from initial diagnosis are eligible for the&#xD;
             study. Patients may not have received anthracycline-based chemotherapy in the past.&#xD;
             Patients with history of ductal carcinoma in situ(DCIS) are eligible if there were&#xD;
             treated with surgery alone&#xD;
&#xD;
          -  History of previous or current malignancy at other sites with the exception of&#xD;
             adequately treated carcinoma in-situ of the cervix or basal or squamous cell carcinoma&#xD;
             of the skin. Patients with a history of other malignancies, who remain disease free&#xD;
             for greater than five years are eligible&#xD;
&#xD;
          -  Uncontrolled blood pressure, previous exposure to apatinib, known allergies to any of&#xD;
             the excipients, and a history of unstable angina, myocardial infarction, or class&#xD;
             III/IV congestive heart failure (defined by the New York Heart Association) within the&#xD;
             past 6 months before day 1 of the trial&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kun Wang</last_name>
    <role>Study Director</role>
    <affiliation>Guangdong Provincial People's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Guangdong general hospital</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510080</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Guangdong General Hospital</name>
      <address>
        <city>Guangzhou</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>August 5, 2017</study_first_submitted>
  <study_first_submitted_qc>August 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 9, 2017</study_first_posted>
  <last_update_submitted>January 29, 2022</last_update_submitted>
  <last_update_submitted_qc>January 29, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Guangdong Provincial People's Hospital</investigator_affiliation>
    <investigator_full_name>Kun Wang</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Triple-Negative Breast Cancer</keyword>
  <keyword>apatinib</keyword>
  <keyword>pCR</keyword>
  <keyword>OS</keyword>
  <keyword>Neoadjuvant chemotherapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Triple Negative Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Apatinib</mesh_term>
  </intervention_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/NCT03243838
org study id: 20170328
nct id: NCT03243838
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Triple-negative breast cancer (TNBC) is a special type of breast cancer, endocrine therapy
      and targeted therapy are completely ineffective, chemotherapy is currently the only effective
      treatment. How to improve postoperative pathologic complete response（pCR）of neoadjuvant
      chemotherapy is critical problem to prolong event-free survival (EFS) and overall survival
      (OS) of TNBC patients. Apatinib is a new oral small molecule tyrosine protease inhibitor, it
      is effective in inhibiting angiogenesis with a very low concentration. So the standard
      neoadjuvant chemotherapy regimen of docetaxel and carboplatin combined with apatinib may
      improve the postoperative pCR and survival outcomes of TNBC patients. Safety and tolerability
      assessed by number of grade 3 and 4 toxicities and hospitalizations.
All enrolled patients were administered oral apatinib at a dose of 250 mg once daily and
      intravenously docetaxel (100 mg/m2) every three weeks for four cycles, followed by epirubicin
      (90 mg/m2) plus cyclophosphamide (600 mg/m2) every three weeks for four cycles. All the
      treatments were continued until disease progression, patient withdrawal, or unacceptable
      toxic effects. Granulocyte colony-stimulating factor (G-CSF) used for prophylaxis of febrile
      neutropenia was permitted according to the American Society of Clinical Oncology (ASCO)
      guidelines. The biochemical and hematological indexes were evaluated every cycle. Dose
      modifications of chemotherapy agents, including dose interruptions and dose reductions, were
      permitted due to certain adverse events.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The pathological complete response (pCR) rate in the breast and lymph nodes (ypTis/0ypN0)
time frame: up to 24 weeks (at the end of cycle 8, each cycle is 21 days)
description: Absence of invasive tumor cells in the breast and lymph nodes and was determined by a local pathologist
measure: Objective response rate (ORR)
time frame: up to 24 weeks (at the end of cycle 8, each cycle is 21 days)
description: ORR was assessed according to RECIST version 1.1, which included patients with measurable disease who achieved a complete or partial response of target lesions.
measure: Event-free survival (EFS)
time frame: up to 24 months
description: The interval from the start of treatment to progression prior to surgery, post-surgery recurrence, or death due to any cause
measure: Overall survival (OS)
time frame: up to 24 months
description: The time from registration to death from any cause
measure: Adverse events
time frame: up to 24 weeks
description: The treatment-related adverse events were assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI-CTCAE 4.0).
arm group label: Experimental Group
arm group type: Experimental
description: Four cycles of docetaxel combined with apatinib followed by four cycles of epirubicin and cyclophosphamide as Neoadjuvant Treatment for Triple-Negative Breast Cancer
intervention type: Drug
intervention name: Apatinib
description: All enrolled patients were administered oral apatinib at a dose of 250 mg once daily and intravenously docetaxel (100 mg/m2) every three weeks for four cycles, followed by epirubicin (90 mg/m2) plus cyclophosphamide (600 mg/m2) every three weeks for four cycles. All the treatments were continued until disease progression, patient withdrawal, or unacceptable toxic effects.
arm group label: Experimental Group
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Kun Wang
role: Study Director
affiliation: Guangdong Provincial People's Hospital
facility: 
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Guangdong Provincial People's Hospital
investigator full name: Kun Wang
investigator title: Professor
mesh term: Breast Neoplasms
mesh term: Triple Negative Breast Neoplasms
mesh term: Apatinib