<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/NCT04452370</url>
  </required_header>
  <id_info>
    <org_study_id>NCC2225</org_study_id>
    <nct_id>NCT04452370</nct_id>
  </id_info>
  <brief_title>Oral Etoposide Combined With Anlotinib in Advanced Triple Negative Breast Cancer</brief_title>
  <official_title>Oral Etoposide Combined With Anlotinib in Advanced Triple Negative Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</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>
      The hypothesis of this study is to discover if the oral Etoposide plus Anlotinib can shrink&#xD;
      or slow the growth of pretreated advanced TNBC.&#xD;
&#xD;
      It is a single-arm, multicenter phase II clinical study of oral etoposide combined with&#xD;
      antinib in the treatment of recurrent or metastatic triple-negative breast cancer&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      It is a single-arm, multicenter phase II clinical study of oral etoposide combined with&#xD;
      antinib in the treatment of recurrent or metastatic triple-negative breast cancer.&#xD;
&#xD;
      The hypothesis of this study is to discover if the oral Etoposide plus Anlotinib can shrink&#xD;
      or slow the growth of pretreated advanced TNBC.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">September 23, 2020</start_date>
  <completion_date type="Anticipated">July 11, 2023</completion_date>
  <primary_completion_date type="Anticipated">July 11, 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>objective response rate（ORR）</measure>
    <time_frame>up to 1 year after the last patient enrolled</time_frame>
    <description>The ORR will be defined as the proportion of patients in the Efficacy Evaluable patient Set who achieve complete response (CR) and partial response (PR)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression free survival（PFS）</measure>
    <time_frame>up to 1 year after the last patient enrolled</time_frame>
    <description>PFS will be defined as the time from first dose of study drug until documentation of disease progression or death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence and Severity of adverse events</measure>
    <time_frame>approximately 1.5 years</time_frame>
    <description>hematologic，hepatotoxicity，Incidence of hypertension，Incidence of proteinuria</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Triple Negative Breast Cancer</condition>
  <arm_group>
    <arm_group_label>oral Etoposide+Anlotinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>anlotinib 12mg qd, d1-14，21days/cycle oral etoposide 75mg qd，d1-10，21days/cycle</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>oral etoposide + anlotinib</intervention_name>
    <description>anlotinib 12mg qd, d1-14，21days/cycle oral etoposide 75mg qd，d1-10，21days/cycle</description>
    <arm_group_label>oral Etoposide+Anlotinib</arm_group_label>
    <other_name>there is no other intervention name</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age between 18 and 75 year-old women; TNBC&#xD;
&#xD;
          -  ECOG score: 0-1, expected survival time ≥ 3months;&#xD;
&#xD;
          -  Pathologically or cytologically confirmed breast cancer;&#xD;
&#xD;
          -  Anthracycline- / taxane- pretreated (adjuvant, neoadjuvant) breast cancer patients who&#xD;
             have failed from 1-3 standard chemotherapies after recurrence and metastasis;&#xD;
&#xD;
          -  According to RECIST 1.1, exist at least ≥1 measurable lesion(CT &gt;1cm，other examination&#xD;
             &gt;2cm);&#xD;
&#xD;
          -  The patients have enough organ function. The laboratory test indexes must comply with&#xD;
             the following requirements:&#xD;
&#xD;
               -  Blood routine: neutrophil≥1.5G/L, platelet count ≥80G/L, hemoglobin ≥90g/L&#xD;
&#xD;
               -  Liver function: serum bilirubin ≤ 1.5 times the upper limit of normal value; ALT&#xD;
                  and AST≤2.5 times the upper limit of normal value; ALT and AST≤5 times the upper&#xD;
                  limit of normal value when liver metastasis&#xD;
&#xD;
               -  Renal function: serum creatinine ≤ 1.0times the upper limit of normal value,&#xD;
                  creatinine clearance &gt;50ml/min（Cockcroft-Gault formula)&#xD;
&#xD;
          -  Women of child-bearing age should be carried out pregnancy test (serum or urine)&#xD;
             within 7 days before recruit, the results should be negative; and are willing to adopt&#xD;
             the appropriate methods of contraception during the trial and 8 weeks after last&#xD;
             administration；&#xD;
&#xD;
          -  Can swallow oral drugs;&#xD;
&#xD;
          -  The patients have good compliance to the therapy and follow-up to be scheduled and are&#xD;
             able to understand the study protocol and sign the Informed Consent Form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  The patients in pregnancy or lactation growth period and did not take effective&#xD;
             contraception;&#xD;
&#xD;
          -  The patients who received ≥4 chemotherapies after recurrence and metastasis; involved&#xD;
             in other clinical trials four weeks prior to the start of the study;&#xD;
&#xD;
          -  The patients with a variety of factors that affect the oral administration and&#xD;
             absorption of drugs;&#xD;
&#xD;
          -  Prior treatment with etoposide or antiangiogenic TKI (subjects with prior use of&#xD;
             antiangiogenic macromolecules such as bevacizumab are allowed to be enrolled);&#xD;
&#xD;
          -  The patients have uncontrollable mental illness；&#xD;
&#xD;
          -  Serous cavity effusion (such as pleural effusion and ascites) with clinical symptoms&#xD;
             requiring clinical intervention or stable time less than 4 weeks;&#xD;
&#xD;
          -  The patients who had serious adverse effect to oral etoposide or were allergic to&#xD;
             etoposide.&#xD;
&#xD;
          -  The patients who have only bone metastasis without other measurable lesion;&#xD;
&#xD;
          -  The patients experience severe cardiovascular diseases;&#xD;
&#xD;
          -  The patients experience severe upper gastrointestinal ulcer or malabsorption syndrome.&#xD;
&#xD;
          -  Abnormal bone marrow functions(neutrophil&lt;1.5G/L, platelet count &lt;75G/L, hemoglobin&#xD;
             &lt;90g/L);&#xD;
&#xD;
          -  Abnormal renal function(serum creatinine &gt; 1.5 times the upper limit of normal value);&#xD;
&#xD;
          -  Abnormal liver function(serum bilirubin ≤ 1.5 times the upper limit of normal value);&#xD;
&#xD;
          -  The patients have uncontrollable brain metastasis;&#xD;
&#xD;
          -  Active or uncontrolled infection requiring systematic treatment (except simple urinary&#xD;
             tract infection or upper respiratory tract infection) during the 2 weeks or 2 weeks&#xD;
             prior to enrollment;&#xD;
&#xD;
          -  Previous or concurrent history of other malignant tumors.Except for the cured skin&#xD;
             basal cell carcinoma and cervical carcinoma in situ;&#xD;
&#xD;
          -  The patients do have good compliance to the therapy.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Peng Yuan</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Peng Yuan</last_name>
    <phone>01087787245</phone>
    <email>yuanpeng01@hotmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Cancer Institute &amp; Hospital. Chinese Academy of Medical Sciences</name>
      <address>
        <city>Beijing</city>
        <zip>100021</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Peng Yuan, M.D.</last_name>
      <phone>86-10-8778 8114</phone>
      <email>yuanpeng01@hotmail.com</email>
    </contact>
    <investigator>
      <last_name>Binghe Xu, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Peng Yuan, M.D.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>June 11, 2020</study_first_submitted>
  <study_first_submitted_qc>June 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 30, 2020</study_first_posted>
  <last_update_submitted>July 15, 2021</last_update_submitted>
  <last_update_submitted_qc>July 15, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 21, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</investigator_affiliation>
    <investigator_full_name>Peng Yuan</investigator_full_name>
    <investigator_title>Principal Investigator</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>Triple Negative Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Etoposide</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/NCT04452370
org study id: NCC2225
nct id: NCT04452370
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The hypothesis of this study is to discover if the oral Etoposide plus Anlotinib can shrink
      or slow the growth of pretreated advanced TNBC.

      It is a single-arm, multicenter phase II clinical study of oral etoposide combined with
      antinib in the treatment of recurrent or metastatic triple-negative breast cancer
It is a single-arm, multicenter phase II clinical study of oral etoposide combined with
      antinib in the treatment of recurrent or metastatic triple-negative breast cancer.

      The hypothesis of this study is to discover if the oral Etoposide plus Anlotinib can shrink
      or slow the growth of pretreated advanced TNBC.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: objective response rate（ORR）
time frame: up to 1 year after the last patient enrolled
description: The ORR will be defined as the proportion of patients in the Efficacy Evaluable patient Set who achieve complete response (CR) and partial response (PR)
measure: Progression free survival（PFS）
time frame: up to 1 year after the last patient enrolled
description: PFS will be defined as the time from first dose of study drug until documentation of disease progression or death from any cause
measure: Incidence and Severity of adverse events
time frame: approximately 1.5 years
description: hematologic，hepatotoxicity，Incidence of hypertension，Incidence of proteinuria
arm group label: oral Etoposide+Anlotinib
arm group type: Experimental
description: anlotinib 12mg qd, d1-14，21days/cycle oral etoposide 75mg qd，d1-10，21days/cycle
intervention type: Drug
intervention name: oral etoposide + anlotinib
description: anlotinib 12mg qd, d1-14，21days/cycle oral etoposide 75mg qd，d1-10，21days/cycle
arm group label: oral Etoposide+Anlotinib
other name: there is no other intervention name
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Peng Yuan
role: Principal Investigator
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
last name: Peng Yuan
phone: 01087787245
email: yuanpeng01@hotmail.com
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
investigator full name: Peng Yuan
investigator title: Principal Investigator
mesh term: Breast Neoplasms
mesh term: Triple Negative Breast Neoplasms
mesh term: Etoposide