<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/NCT04447118</url>
  </required_header>
  <id_info>
    <org_study_id>HR-BLTN-III-NSCLC</org_study_id>
    <nct_id>NCT04447118</nct_id>
  </id_info>
  <brief_title>Phase 3 Study of Pyrotinib Versus Docetaxel in Patients With Advanced Non-squamous NSCLC Harboring a HER2 Exon 20 Mutation Who Failed Platinum Based Chemotherapy</brief_title>
  <acronym>PYRAMID-1</acronym>
  <official_title>A Phase 3, Randomized, Open-label, Multicenter Study of the Efficacy and Safety of Pyrotinib Versus Docetaxel in Patients With Advanced Non-squamous Non-small Cell Lung Cancer (NSCLC) Harboring a HER2 Exon 20 Mutation Who Progressed on or After Treatment With Platinum Based Chemotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jiangsu HengRui Medicine Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Jiangsu HengRui Medicine Co., Ltd.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomized, positive-controlled, open-label, international multicenter, Phase 3&#xD;
      clinical study to compare the efficacy and safety of pyrotinib versus docetaxel in patients&#xD;
      with advanced non-squamous NSCLC harboring a HER2 exon 20 mutation who failed platinum based&#xD;
      chemotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      150 eligible subjects will be randomized in a 2:1 ratio (Study treatment Arm: Control Arm =&#xD;
      100 : 50 subjects) to receive pyrotinib or docetaxel monotherapy.&#xD;
&#xD;
      Each treatment cycle is defined as 21 days for subjects in both arms. Treatment regimen of&#xD;
      pyrotinib (Study treatment Arm): 400 mg/d (QD) oral pyrotinib will be administered within 30&#xD;
      minutes after completion of a meal.&#xD;
&#xD;
      Treatment regimen of docetaxel (Control Arm): 75 mg/m2 (Q3W) of docetaxel will be&#xD;
      administered via intravenous infusion.&#xD;
&#xD;
      In this study, crossover treatment is allowed for subjects in Control Arm. Within the&#xD;
      specified time window of each cycle, subjects should complete physical examinations,&#xD;
      laboratory tests, quality of life questionnaires and other tests to assess the safety and&#xD;
      quality of life of the subjects.&#xD;
&#xD;
      During study treatment, tumor radiological assessments will be performed every 6 weeks (42 ±&#xD;
      7 days) in the first 52 weeks and every 12 weeks (84 ± 7 days) thereafter.&#xD;
&#xD;
      After the end of treatment and safety follow-up, all subjects will be followed for survival&#xD;
      (every 56 ± 7 days) until death, withdrawal of informed consent, lost to follow-up, or&#xD;
      termination of the study (whichever occurs first).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 11, 2020</start_date>
  <completion_date type="Anticipated">October 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2023</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>Single (Outcomes Assessor)</masking>
    <masking_description>In this study, the Blinded Independent Review Committee (BIRC) will perform a blinded evaluation on the primary endpoint.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>26 months</time_frame>
    <description>Time from the date of randomization to the date of first disease progression documented by BIRC according to the RECIST v1.1 or death for any cause, whichever comes first.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>36 months</time_frame>
    <description>Time from the date of randomization to death for any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>26 months</time_frame>
    <description>Assessed by BIRC and investigator according to the RECIST v1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate (DCR)</measure>
    <time_frame>26 months</time_frame>
    <description>Assessed by BIRC and investigator according to the RECIST v1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DoR)</measure>
    <time_frame>26 months</time_frame>
    <description>Assessed by BIRC and investigator according to the RECIST v1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to tumor progression (TTP)</measure>
    <time_frame>26 months</time_frame>
    <description>Assessed by BIRC and investigator according to the RECIST v1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival 2(PFS2)</measure>
    <time_frame>36 months</time_frame>
    <description>Assessed by investigator according to the RECIST v1.1, or death for any cause, whichever comes first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient reported outcome (PRO) using EORTC QLQ-C30</measure>
    <time_frame>26 months</time_frame>
    <description>Symptoms related to NSCLC,</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient reported outcomes (PRO) using the QLQ-LC13</measure>
    <time_frame>26 months</time_frame>
    <description>Symptoms related to NSCLC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma concentrations of pyrotinib</measure>
    <time_frame>26 months</time_frame>
    <description>Pharmacokinetics (PK) of pyrotinib</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AEs and SAEs</measure>
    <time_frame>26 months</time_frame>
    <description>Judged in accordance with NCI-CTCAE v5.0</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">151</enrollment>
  <condition>Non-squamous NSCLC</condition>
  <condition>HER2 Exon 20 Mutation</condition>
  <arm_group>
    <arm_group_label>Study treatment Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pyrotinib maleate tablet, 400 mg, once daily (QD)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Docetaxel injection, 75 mg/m2, once every 3 weeks (Q3W)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pyrotinib</intervention_name>
    <description>400 mg, once daily (QD), will be administered with water within 30 minutes after completion of a meal, at approximately the same time each day on a continuous daily dosing schedule, with 21 days as a cycle.</description>
    <arm_group_label>Study treatment Arm</arm_group_label>
    <other_name>Irene</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Docetaxel</intervention_name>
    <description>75 mg/m2, once every 3 weeks (Q3W), will be administered by intravenous infusion over 1 hour, with 21 days as a cycle.</description>
    <arm_group_label>Control Arm</arm_group_label>
    <other_name>Docetaxel injection</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed and dated written informed consent which is approved by IRB/EC, willing and&#xD;
             able to comply with scheduled treatment, all examinations at study visits, and other&#xD;
             study procedures.&#xD;
&#xD;
          -  ECOG PS 0-1.&#xD;
&#xD;
          -  Have histologically or cytologically confirmed locally advanced or metastatic&#xD;
             non-squamous NSCLC disease.&#xD;
&#xD;
          -  Before enrollment, a documented confirmed presence of activating mutations in exon 20&#xD;
             of the HER2 gene must be provided. Sufficient tumor tissue samples should be provided&#xD;
             to retrospectively confirm the mutation status of the HER2 gene.&#xD;
&#xD;
          -  Must have measureable disease per RECIST v1.1.&#xD;
&#xD;
          -  For advanced NSCLC, patients must have had progressive disease on or after a platinum&#xD;
             based chemotherapy, with or without immune checkpoint inhibitors (PD-1/PD-L1&#xD;
             inhibitors) and/or anti-angiogenic drugs. No more than 2 prior lines of systemic&#xD;
             therapy are allowed.&#xD;
&#xD;
          -  The laboratory test values must meet the following standards to manifest that the&#xD;
             functional level of important organs/systems meets the requirements.&#xD;
&#xD;
          -  Female patient of childbearing potential (WOCBP) and male patient whose - partner is&#xD;
             WOCBP must agree to use effective contraception method during the study period.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Malignant tumors with other pathological types.&#xD;
&#xD;
          -  Medical history of other active malignancies within last 5 years.&#xD;
&#xD;
          -  Subjects with active CNS metastases.&#xD;
&#xD;
          -  Previously treated with targeted drugs for HER2 gene mutations,or previously treated&#xD;
             with docetaxel.&#xD;
&#xD;
          -  Prior to the first dose of study treatment, patients with severe effusions with&#xD;
             clinical symptoms, severe cardiac disease, or severe infection.&#xD;
&#xD;
          -  Prior to the first dose of study treatment, patients with diseases or special&#xD;
             conditions that affect drug administration and absorption.&#xD;
&#xD;
          -  Congenital or acquired immunodeficiency.&#xD;
&#xD;
          -  History of allergy to the study drugs or components.&#xD;
&#xD;
          -  Prior to the first dose of study treatment, or during the study period, patients&#xD;
             receive or are anticipated to receive continuous strong CYP3A4 inducers or inhibitors,&#xD;
             P-gp inhibitors, or medications that are known to cause QT/QTc prolongation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wei Shi, MD,PhD</last_name>
    <role>Study Director</role>
    <affiliation>Jiangsu Hengrui Pharmaceuticals Co.,Ltd</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California - Irvine Medical Center</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California (UC) Davis Comprehensive Cancer Center</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Innovative Clinical Research Institute</name>
      <address>
        <city>Whittier</city>
        <state>California</state>
        <zip>33756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists South Divisio</name>
      <address>
        <city>Fort Myers</city>
        <state>Florida</state>
        <zip>33901</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists North Divisio</name>
      <address>
        <city>Saint Petersburg</city>
        <state>Florida</state>
        <zip>33701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Medical Center (KUMC)</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gabrail Cancer Center</name>
      <address>
        <city>Canton</city>
        <state>Ohio</state>
        <zip>44718</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tennessee Oncology</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>33756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Summit Cancer Centers - North Spokane</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal North Shore Hospital</name>
      <address>
        <city>St Leonards</city>
        <state>Saint Leonards</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Border Medical Oncology</name>
      <address>
        <city>Albury</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Vincent's Hospital Melbourne</name>
      <address>
        <city>Fitzroy</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sir Charles Gairdner Hospital</name>
      <address>
        <city>Nedlands</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Calvary North Adelaide Hospital</name>
      <address>
        <city>North Adelaide</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Antwerp University Hospital (UZA)</name>
      <address>
        <city>Edegem</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Gent</name>
      <address>
        <city>Gent</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital (UZ) Leuven</name>
      <address>
        <city>Leuven</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>the Second Affiliated Hospital of Anhui Medical University</name>
      <address>
        <city>Hefei</city>
        <state>Anhui</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>beijing chest hospital,Capital medical university</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Peking university Cancer Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The second affiliated hospital of ChongQing medical university</name>
      <address>
        <city>Chongqing</city>
        <state>Chongqing</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Affiliated Hospital of Guangdong Pharmaceutical University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cangzhou Hospital of Integrated Tcm-Wm.Hebei</name>
      <address>
        <city>Cangzhou</city>
        <state>Hebei</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Harbin Medical University Cancer Hospital</name>
      <address>
        <city>Ha'erbin</city>
        <state>Heilongjiang</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>First Affiliated Hospital of ZhengzhouUniversity</name>
      <address>
        <city>Zhengzhou</city>
        <state>Henan</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henan Cancer Hospital</name>
      <address>
        <city>Zhengzhou</city>
        <state>Henan</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hubei cancer hospital WardII</name>
      <address>
        <city>Wuhan</city>
        <state>Hubei</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hunan Cancer Hospital &amp; The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University</name>
      <address>
        <city>Changsha</city>
        <state>Hunan</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jiangsu Cancer Hospital</name>
      <address>
        <city>Nanjing</city>
        <state>Jiangsu</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Subei People's Hospital of Jiangsu Province</name>
      <address>
        <city>Yangzhou</city>
        <state>Jiangsu</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Second Affiliated of Nanchang University</name>
      <address>
        <city>Nanchang</city>
        <state>Jiangxi</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jilin Cancer Hospital</name>
      <address>
        <city>Changchun</city>
        <state>Jilin</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The affiliated hospital of inner mongolia medical univerity</name>
      <address>
        <city>Hohhot</city>
        <state>Neimenggu</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shandong Cancer Hospital Affiliated to Shandong University</name>
      <address>
        <city>Jinan</city>
        <state>Shandong</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shanghai Pulmonary Hospital, Tongji University</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200433</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fudan University Cancer hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ruijin Hospital, Shanghai Jiaotong University School of Medicine</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shanghai Chest Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shanxi Provincial Cancer Hospital</name>
      <address>
        <city>Taiyuan</city>
        <state>Shanxi</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SiChuan Cancer Hospital</name>
      <address>
        <city>Chengdu</city>
        <state>Sichuan</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West China Hospital,Sichuan University</name>
      <address>
        <city>Chengdu</city>
        <state>Sichuan</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Second People's Hosipital of Yibin</name>
      <address>
        <city>Yibin</city>
        <state>Sichuan</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>General Hospital of Tianjin Medical University</name>
      <address>
        <city>Tianjin</city>
        <state>Tianjin</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yunnan Provincial Cancer Hospital</name>
      <address>
        <city>Kunming</city>
        <state>Yunnan</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sir Run Run Shaw Hospital ZheJiang University School Of Medicine</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Affiliated Hospital，ZheJiang University</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ZheJiang Cancer Hospital</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taizhou Hospital of Zhejiang Province</name>
      <address>
        <city>Taizhou</city>
        <state>Zhejiang</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Francois Baclesse</name>
      <address>
        <city>CAEN cedex 05</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Intercommunal Creteil</name>
      <address>
        <city>Creteil</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AP-HM - Hôpital Nord</name>
      <address>
        <city>Marseille cedex 20</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Bichat - Claude Bernard - AP-HP</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHRU Strasbourg</name>
      <address>
        <city>Strasbourg Cedex</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Toulouse - Hopital Larrey</name>
      <address>
        <city>Toulouse</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Carl Gustav Carus Dresden</name>
      <address>
        <city>Dresden</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniklinikum Giessen und Marburg</name>
      <address>
        <city>Giessen</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikverbund Kempten-Oberallgäu gGmbH</name>
      <address>
        <city>Kempten</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>POIS Leipzig GbR</name>
      <address>
        <city>Leipzig</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pius-Hospital Oldenburg, Centre of Radiotherapy and Medical Oncology, Dept. Medical Oncology</name>
      <address>
        <city>Oldenburg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Riferimento Oncologico - Aviano</name>
      <address>
        <city>Aviano</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero Universitaria Policlinico G. Rodolico-San Marco - Presidio Ospedaliero G. Rodolico</name>
      <address>
        <city>Catania</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Romagnolo per lo Studio dei Tumori Dino Amadori</name>
      <address>
        <city>Meldola (fc)</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Europeo di Oncologia</name>
      <address>
        <city>Milano</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ASST dei Sette Laghi-Ospedale di Circolo e Fondazione Macchi di Varese</name>
      <address>
        <city>Varese</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Bundang Hospital</name>
      <address>
        <city>Seoul</city>
        <state>Bundang</state>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ajou University Hospital</name>
      <address>
        <city>Gyeonggi-do</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asan Medical Center</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Korea University Anam Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samsung Medical Center</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul St. Mary's Hospital, The Catholic University of Korea</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Severance Hospital, Yonsei University Health System</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrum Onkologii KOMED</name>
      <address>
        <city>Konin</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Salve-Medica</name>
      <address>
        <city>Lodz</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instytut Genetyki i Immunologii GENIM</name>
      <address>
        <city>Lublin</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Med Polonia Sp. z o.o.</name>
      <address>
        <city>Poznan</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Petrov National Medical Research Center of Oncology</name>
      <address>
        <city>St. Petersburg</city>
        <state>Saint Petersburg</state>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arkhangelsk Clinical Oncological Dispensary</name>
      <address>
        <city>Arkhangelsk</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>JSC Group of companies Medsi</name>
      <address>
        <city>Moscow</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical hospital RZD-Medicine of St. Petersburg</name>
      <address>
        <city>Saint Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eurocityclinic LLC</name>
      <address>
        <city>Saint Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint-Petersburg Clinical Research Center of Specialized Types of Medical Care (Oncology)</name>
      <address>
        <city>Saint Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Germans Trias i Pujol</name>
      <address>
        <city>Barcelona</city>
        <state>Badalona</state>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <state>Badalona</state>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinic Barcelona</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Fundación Jiménez Díaz</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario 12 de Octubre</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Regional Universitario de Malaga</name>
      <address>
        <city>Malaga</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Complejo Hospitalario de Navarra</name>
      <address>
        <city>Pamplona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen del Rocio</name>
      <address>
        <city>Sevilla</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Valenciano de Oncologia</name>
      <address>
        <city>Valencia</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>China Medical University Hospital</name>
      <address>
        <city>Taichung</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taipei Veterans General Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Linkou Chang Gung Memorial Hospital (CGMHLK)</name>
      <address>
        <city>Taoyuan City</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baskent University Adana Application and Research Center</name>
      <address>
        <city>Adana</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ankara Sehir Hastanesi</name>
      <address>
        <city>Ankara</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istanbul University Cerrahpasa Medical Faculty</name>
      <address>
        <city>Istanbul</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Izmir Medical Park Hospital</name>
      <address>
        <city>Izmir</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gulhane Training and Research Hospital</name>
      <address>
        <city>Keçiören</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Necmettin Erbakan University Selcuklu Faculty of Medicine</name>
      <address>
        <city>Konya</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Trakya University Medical Faculty</name>
      <address>
        <city>Merkez</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Belgium</country>
    <country>China</country>
    <country>France</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Korea, Republic of</country>
    <country>Poland</country>
    <country>Russian Federation</country>
    <country>Spain</country>
    <country>Taiwan</country>
    <country>Turkey</country>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>June 23, 2020</study_first_submitted>
  <study_first_submitted_qc>June 24, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 25, 2020</study_first_posted>
  <last_update_submitted>March 7, 2023</last_update_submitted>
  <last_update_submitted_qc>March 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>pyrotinib</keyword>
  <keyword>docetaxel</keyword>
  <keyword>HER2 Exon 20 Mutation</keyword>
  <keyword>NSCLC</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Docetaxel</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/NCT04447118
org study id: HR-BLTN-III-NSCLC
nct id: NCT04447118
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a randomized, positive-controlled, open-label, international multicenter, Phase 3
      clinical study to compare the efficacy and safety of pyrotinib versus docetaxel in patients
      with advanced non-squamous NSCLC harboring a HER2 exon 20 mutation who failed platinum based
      chemotherapy.
150 eligible subjects will be randomized in a 2:1 ratio (Study treatment Arm: Control Arm =
      100 : 50 subjects) to receive pyrotinib or docetaxel monotherapy.

      Each treatment cycle is defined as 21 days for subjects in both arms. Treatment regimen of
      pyrotinib (Study treatment Arm): 400 mg/d (QD) oral pyrotinib will be administered within 30
      minutes after completion of a meal.

      Treatment regimen of docetaxel (Control Arm): 75 mg/m2 (Q3W) of docetaxel will be
      administered via intravenous infusion.

      In this study, crossover treatment is allowed for subjects in Control Arm. Within the
      specified time window of each cycle, subjects should complete physical examinations,
      laboratory tests, quality of life questionnaires and other tests to assess the safety and
      quality of life of the subjects.

      During study treatment, tumor radiological assessments will be performed every 6 weeks (42 ±
      7 days) in the first 52 weeks and every 12 weeks (84 ± 7 days) thereafter.

      After the end of treatment and safety follow-up, all subjects will be followed for survival
      (every 56 ± 7 days) until death, withdrawal of informed consent, lost to follow-up, or
      termination of the study (whichever occurs first).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: In this study, the Blinded Independent Review Committee (BIRC) will perform a blinded evaluation on the primary endpoint.
measure: Progression-free survival (PFS)
time frame: 26 months
description: Time from the date of randomization to the date of first disease progression documented by BIRC according to the RECIST v1.1 or death for any cause, whichever comes first.
measure: Overall survival (OS)
time frame: 36 months
description: Time from the date of randomization to death for any cause.
measure: Objective response rate (ORR)
time frame: 26 months
description: Assessed by BIRC and investigator according to the RECIST v1.1.
measure: Disease control rate (DCR)
time frame: 26 months
description: Assessed by BIRC and investigator according to the RECIST v1.1.
measure: Duration of response (DoR)
time frame: 26 months
description: Assessed by BIRC and investigator according to the RECIST v1.1.
measure: Time to tumor progression (TTP)
time frame: 26 months
description: Assessed by BIRC and investigator according to the RECIST v1.1.
measure: Progression-free survival 2(PFS2)
time frame: 36 months
description: Assessed by investigator according to the RECIST v1.1, or death for any cause, whichever comes first.
measure: Patient reported outcome (PRO) using EORTC QLQ-C30
time frame: 26 months
description: Symptoms related to NSCLC,
measure: Patient reported outcomes (PRO) using the QLQ-LC13
time frame: 26 months
description: Symptoms related to NSCLC
measure: Plasma concentrations of pyrotinib
time frame: 26 months
description: Pharmacokinetics (PK) of pyrotinib
measure: AEs and SAEs
time frame: 26 months
description: Judged in accordance with NCI-CTCAE v5.0
arm group label: Study treatment Arm
arm group type: Experimental
description: Pyrotinib maleate tablet, 400 mg, once daily (QD)
arm group label: Control Arm
arm group type: Active Comparator
description: Docetaxel injection, 75 mg/m2, once every 3 weeks (Q3W)
intervention type: Drug
intervention name: Pyrotinib
description: 400 mg, once daily (QD), will be administered with water within 30 minutes after completion of a meal, at approximately the same time each day on a continuous daily dosing schedule, with 21 days as a cycle.
arm group label: Study treatment Arm
other name: Irene
intervention type: Drug
intervention name: Docetaxel
description: 75 mg/m2, once every 3 weeks (Q3W), will be administered by intravenous infusion over 1 hour, with 21 days as a cycle.
arm group label: Control Arm
other name: Docetaxel injection
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Wei Shi, MD,PhD
role: Study Director
affiliation: Jiangsu Hengrui Pharmaceuticals Co.,Ltd
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country: Australia
country: Belgium
country: China
country: France
country: Germany
country: Italy
country: Korea, Republic of
country: Poland
country: Russian Federation
country: Spain
country: Taiwan
country: Turkey
country: United States
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Docetaxel
sharing ipd: No