<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/NCT03002103</url>
  </required_header>
  <id_info>
    <org_study_id>CT4005</org_study_id>
    <nct_id>NCT03002103</nct_id>
  </id_info>
  <brief_title>A Trial Evaluating the Efficacy and Safety of EndoTAG®-1 in Combination With Paclitaxel and Gemcitabine Compared With Paclitaxel and Gemcitabine as First-line Therapy in Patients With Visceral Metastatic Triple-negative Breast Cancer</brief_title>
  <official_title>An Open-label, Randomized, Controlled Phase III Trial Evaluating the Efficacy and Safety of EndoTAG®-1 in Combination With Paclitaxel and Gemcitabine Compared With Paclitaxel and Gemcitabine as First-line Therapy in Patients With Visceral Metastatic Triple-negative Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>SynCore Biotechnology Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>SynCore Biotechnology Co., Ltd.</source>
  <brief_summary>
    <textblock>
      This is a prospective, multicenter, open-label, randomized, and controlled trial to test the&#xD;
      superiority of EndoTAG®-1 in combination with paclitaxel and gemcitabine versus paclitaxel in&#xD;
      combination with gemcitabine.&#xD;
&#xD;
      An independent data safety monitoring board (DSMB) will be established to decide on the&#xD;
      recommended dose (RD) of EndoTAG®-1, paclitaxel and gemcitabine to be used throughout the&#xD;
      trial and to monitor the patients' safety and treatment efficacy data&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Suspended</overall_status>
  <why_stopped>
    study design reconsideration&#xD;
  </why_stopped>
  <start_date type="Actual">November 23, 2016</start_date>
  <completion_date type="Anticipated">June 2027</completion_date>
  <primary_completion_date type="Anticipated">March 2025</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>PFS</measure>
    <time_frame>up to 12 months</time_frame>
    <description>Progression free survival defined as the time from randomization to disease progression based on blinded central radiological image evaluation according to response evaluation criteria in solid tumors (RECIST, version 1.1) or death from any cause, whichever occurs first</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>24 months</time_frame>
    <description>from randomization to death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical benefit rate</measure>
    <time_frame>up to 24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best overall tumor response rate</measure>
    <time_frame>up to 24 months</time_frame>
    <description>objective response or SD of any duration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response</measure>
    <time_frame>up to 24 months</time_frame>
    <description>the time from randomization to disease progression in the subgroup of patients responding to therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life(QLQ-C30,QLQ-BR23)</measure>
    <time_frame>up to 24 months</time_frame>
    <description>until disease progression</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-progression PFS</measure>
    <time_frame>up to 12 months</time_frame>
    <description>as the time from start of second and subsequent lines of therapy administered after trial participation to disease progression (based on local radiological image evaluation or clinical assessment) or death from any cause, whichever occurs first</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">420</enrollment>
  <condition>Triple-Negative Breast Cancer</condition>
  <arm_group>
    <arm_group_label>ET+P+G</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EndoTAG-1</intervention_name>
    <arm_group_label>ET+P+G</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>ET+P+G</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine Hydrochloride</intervention_name>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>ET+P+G</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Gender: Female&#xD;
&#xD;
          2. Age ≥ 18 years or legal age to provide informed consent according to local regulatory&#xD;
             requirements.&#xD;
&#xD;
          3. Metastatic TNBC confirmed histologically by a certified local laboratory (or existing&#xD;
             medical record for confirmation is acceptable for patients in the safety run-in stage)&#xD;
             using archival paraffinated material from the original surgery specimens or from later&#xD;
             materials, if available. Results of the certified local laboratory must be available&#xD;
             to allow for randomization.&#xD;
&#xD;
             Tumors should be considered negative for ER and PrR by immunohistochemistry (IHC) (&lt;&#xD;
             1% positive tumor nuclei, as per American Society of Clinical Oncology/College of&#xD;
             American Pathologists [ASCO/CAP] guideline recommendations, Hammond et al 2010) and&#xD;
             negative for HER2 by IHC or fluorescent or chromogenic in situ hybridization (FISH or&#xD;
             CISH). Patients with equivocal HER2 results by IHC should have the negativity status&#xD;
             confirmed by FISH.&#xD;
&#xD;
          4. Patients must have had prior adjuvant treatment with either sequential or concurrent&#xD;
             anthracycline- and/or taxane-based chemotherapy. Patients may have received&#xD;
             neoadjuvant treatment prior to the adjuvant anthracycline- and/or taxane-based&#xD;
             chemotherapy as well.&#xD;
&#xD;
             Note: Neoadjuvant treatment alone is acceptable only for patients in the safety run-in&#xD;
             stage.&#xD;
&#xD;
          5. Patients with a disease-free interval (DFI) on anthracycline- and/or taxane-based&#xD;
             adjuvant therapy of ≥ 12 months.&#xD;
&#xD;
             Note: This criteria is for main study only.&#xD;
&#xD;
          6. Patients must be indicated for treatment with polychemotherapy for visceral metastatic&#xD;
             disease as judged by the Investigator.&#xD;
&#xD;
             Note: Lymph node metastasis alone is acceptable only for patients in the safety run-in&#xD;
             stage.&#xD;
&#xD;
          7. At least one measurable or non-measurable tumor lesion according to RECIST version 1.1&#xD;
             as assessed by the Investigator (local radiological image assessment).&#xD;
&#xD;
          8. ECOG performance status 0 or 1.&#xD;
&#xD;
          9. Negative pregnancy test (females of childbearing potential).&#xD;
&#xD;
         10. Willingness to perform double-barrier contraception during study and for 6 months post&#xD;
             chemotherapy treatment (females of childbearing potential).&#xD;
&#xD;
         11. Signed informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior first-line chemotherapy for locally recurrent and/or metastatic breast cancer,&#xD;
             including visceral disease.&#xD;
&#xD;
          2. Brain metastasis/known progressive cerebral metastasis (patients with cerebral&#xD;
             metastases in a stable state or after successful surgical or radiological treatment&#xD;
             are allowed to participate in the study).&#xD;
&#xD;
          3. Major surgery &lt; 4 weeks prior to enrollment.&#xD;
&#xD;
          4. Cancer immunotherapy at any time.&#xD;
&#xD;
          5. Severe pulmonary obstructive or restrictive disease.&#xD;
&#xD;
          6. Uncontrolled inflammatory disease (autoimmune or infectious).&#xD;
&#xD;
          7. Clinically significant cardiac disease (New York Heart Association [NYHA] stadium &gt;&#xD;
             2).&#xD;
&#xD;
          8. Results of laboratory tests (hematology, coagulation, clinical chemistry) outside&#xD;
             specified limits:&#xD;
&#xD;
               -  White blood cell (WBC) count ≤ 3 × 109/L&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≤ 1.5 × 109/L&#xD;
&#xD;
               -  Platelets ≤ 100 × 109/L&#xD;
&#xD;
               -  Hemoglobin (Hb) ≤ 9.0 g/dL (≤ 5.6 mmol/L)&#xD;
&#xD;
               -  Activated partial thromboplastin time/international normalized ratio (aPTT/INR) &gt;&#xD;
                  1.5 × upper limit of normal (ULN)&#xD;
&#xD;
               -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT)&gt; 2.5 × ULN (&gt;&#xD;
                  5 × ULN if presence of liver metastasis)&#xD;
&#xD;
               -  Alkaline phosphatase (AP) &gt; 2 × ULN (&gt; 5 × ULN if presence of liver metastasis)&#xD;
&#xD;
               -  Total bilirubin &gt; 1.5 × ULN (&gt; 2.5 × ULN if presence of liver metastasis)&#xD;
&#xD;
          9. Pregnancy or nursing status.&#xD;
&#xD;
         10. Known positive human immunodeficiency virus (HIV) infection in medical history.&#xD;
&#xD;
         11. Peripheral neuropathy associated to prior taxane therapy not recovered to grade 0 or&#xD;
             1.&#xD;
&#xD;
         12. Known hypersensitivity to any component of the EndoTAG®-1, standard paclitaxel and/or&#xD;
             gemcitabine formulations.&#xD;
&#xD;
         13. History of malignancy other than breast cancer &lt; 5 years prior to enrollment, except&#xD;
             skin cancer (i.e., basal or squamous cell carcinoma) treated locally.&#xD;
&#xD;
         14. History of active or significant neurological disorder or psychiatric disorder that&#xD;
             would prohibit the understanding and giving of informed consent, or would interfere in&#xD;
             the clinical and radiological evaluation of central nervous system during the trial.&#xD;
&#xD;
         15. Concurrent treatment with other experimental products. Participation in another&#xD;
             clinical trial with any investigational product within 30 days prior to study entry.&#xD;
&#xD;
         16. Positive test for hepatitis B (hepatitis B virus surface antigen [HBsAg] positive; or&#xD;
             HBsAg negative but anti-hepatitis B virus core [HBc] antibody positive and HBV DNA&#xD;
             positive) or hepatitis C (anti hepatitis C virus [HCV] antibody positive). Patients&#xD;
             that are anti-HCV antibody positive can also be judged eligible if further HCV RNA&#xD;
             detection shows negative results.&#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>Tsu-Yi Chao, M.D., Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Taipei Medical University Shuang Ho Hospital, New Taipei City, Taiwan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Kaohsiung Veterans General Hospital</name>
      <address>
        <city>Kaohsiung</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taipei Medical University Shuang Ho Hospital</name>
      <address>
        <city>New Taipei City</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taichung Veterans General Hospital</name>
      <address>
        <city>Taichung</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Koo Foundation Sun Yat-Sen Cancer Center</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mackay Memorial Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chang Gung Memorial Hospital, Linkou</name>
      <address>
        <city>Taoyuan</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>December 19, 2016</study_first_submitted>
  <study_first_submitted_qc>December 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 23, 2016</study_first_posted>
  <last_update_submitted>April 24, 2023</last_update_submitted>
  <last_update_submitted_qc>April 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 26, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </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>Paclitaxel</mesh_term>
    <mesh_term>Gemcitabine</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/NCT03002103
org study id: CT4005
nct id: NCT03002103
lead sponsor: 
This is a prospective, multicenter, open-label, randomized, and controlled trial to test the
      superiority of EndoTAG®-1 in combination with paclitaxel and gemcitabine versus paclitaxel in
      combination with gemcitabine.

      An independent data safety monitoring board (DSMB) will be established to decide on the
      recommended dose (RD) of EndoTAG®-1, paclitaxel and gemcitabine to be used throughout the
      trial and to monitor the patients' safety and treatment efficacy data
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: PFS
time frame: up to 12 months
description: Progression free survival defined as the time from randomization to disease progression based on blinded central radiological image evaluation according to response evaluation criteria in solid tumors (RECIST, version 1.1) or death from any cause, whichever occurs first
measure: Overall survival
time frame: 24 months
description: from randomization to death from any cause
measure: Clinical benefit rate
time frame: up to 24 months
measure: Best overall tumor response rate
time frame: up to 24 months
description: objective response or SD of any duration
measure: Duration of response
time frame: up to 24 months
description: the time from randomization to disease progression in the subgroup of patients responding to therapy
measure: Quality of life(QLQ-C30,QLQ-BR23)
time frame: up to 24 months
description: until disease progression
measure: Post-progression PFS
time frame: up to 12 months
description: as the time from start of second and subsequent lines of therapy administered after trial participation to disease progression (based on local radiological image evaluation or clinical assessment) or death from any cause, whichever occurs first
arm group label: ET+P+G
arm group type: Experimental
arm group label: Control
arm group type: Active Comparator
intervention type: Drug
intervention name: EndoTAG-1
arm group label: ET+P+G
intervention type: Drug
intervention name: Paclitaxel
arm group label: Control
arm group label: ET+P+G
intervention type: Drug
intervention name: Gemcitabine Hydrochloride
arm group label: Control
arm group label: ET+P+G
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Tsu-Yi Chao, M.D., Ph.D.
role: Principal Investigator
affiliation: Taipei Medical University Shuang Ho Hospital, New Taipei City, Taiwan
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Taiwan
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Triple Negative Breast Neoplasms
mesh term: Paclitaxel
mesh term: Gemcitabine