<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/NCT04499924</url>
  </required_header>
  <id_info>
    <org_study_id>SGNTUC-022</org_study_id>
    <nct_id>NCT04499924</nct_id>
  </id_info>
  <brief_title>Tucatinib, Trastuzumab, Ramucirumab, and Paclitaxel Versus Paclitaxel and Ramucirumab in Previously Treated HER2+ Gastroesophageal Cancer</brief_title>
  <acronym>MOUNTAINEER-02</acronym>
  <official_title>A Randomized, Double-blind, Placebo-controlled, Active Comparator Phase 2/3 Study of Tucatinib in Combination With Trastuzumab, Ramucirumab, and Paclitaxel in Subjects With Previously Treated, Locally-advanced Unresectable or Metastatic HER2+ Gastric or Gastroesophageal Junction Adenocarcinoma (GEC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Seagen Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Seagen Inc.</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 study is being done to see if tucatinib with trastuzumab, ramucirumab and paclitaxel&#xD;
      works better than ramucirumab and paclitaxel to treat HER2-positive (HER2+) cancer of the gut&#xD;
      (stomach or gastroesophageal cancer). This study will also look at what side effects happen&#xD;
      when participants take this combination of drugs. A side effect is anything the drug does&#xD;
      other than treating cancer.&#xD;
&#xD;
      Study treatment will be given in 28-day cycles.&#xD;
&#xD;
      In the Phase 2 part of the trial, participants and their doctors will know what drugs are&#xD;
      being given (open-label). In the Phase 3 part, the study is &quot;blinded.&quot; This means that&#xD;
      participants, their doctor, and the study sponsor will not know which drugs are being given.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 22, 2021</start_date>
  <completion_date type="Anticipated">March 31, 2027</completion_date>
  <primary_completion_date type="Anticipated">May 31, 2025</primary_completion_date>
  <phase>Phase 2/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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall survival (OS) (Phase 3 only)</measure>
    <time_frame>60 months</time_frame>
    <description>OS is defined as the time from randomization to death due to any cause</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Progression-free survival (PFS) per Response evaluation criteria in solid tumors (RECIST) version 1.1 according to investigator assessment (Phase 3 only)</measure>
    <time_frame>36 months</time_frame>
    <description>PFS is defined as the time from randomization to the date of disease progression or death from any cause</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of dose-limiting toxicities (DLTs) (Phase 2 only)</measure>
    <time_frame>During first cycle of treatment; up to one month</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of adverse events (AEs) (Phase 2 only)</measure>
    <time_frame>18 months</time_frame>
    <description>An adverse event is any untoward medical occurrence in a subject or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of laboratory abnormalities (Phase 2 only)</measure>
    <time_frame>18 months</time_frame>
    <description>To be summarized using descriptive statistics.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of dose modifications (Phase 2 only)</measure>
    <time_frame>18 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Confirmed objective response rate (ORR) per RECIST version 1.1 according to investigator assessment (Phases 2 and 3)</measure>
    <time_frame>36 months</time_frame>
    <description>ORR is defined as the proportion of subjects with best overall response of CR or PR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ORR per RECIST version 1.1 according to investigator assessment (Phases 2 and 3)</measure>
    <time_frame>36 months</time_frame>
    <description>ORR is defined as the proportion of subjects with best overall response of CR or PR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR) per RECIST version 1.1 according to investigator assessment (Phases 2 and 3)</measure>
    <time_frame>36 months</time_frame>
    <description>DOR is defined as the time from first documentation of objective response of CR or PR to the first documentation of disease progression or death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate (DCR) per RECIST version 1.1 according to investigator assessment (Phases 2 and 3)</measure>
    <time_frame>36 months</time_frame>
    <description>DCR is defined as subjects with CR, PR, or stable disease (SD or non-CR/non-progressive disease)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS per RECIST v1.1 according to blinded independent central review (BICR) assessment (Phase 3 only)</measure>
    <time_frame>36 months</time_frame>
    <description>PFS is defined as the time from randomization to the date of disease progression or death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Confirmed ORR per RECIST version 1.1 according to BICR assessment (Phase 3 only)</measure>
    <time_frame>36 months</time_frame>
    <description>ORR is defined as the proportion of subjects with best overall response of CR or PR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ORR per RECIST version 1.1 according to BICR assessment (Phase 3 only)</measure>
    <time_frame>36 months</time_frame>
    <description>ORR is defined as the proportion of subjects with best overall response of CR or PR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DOR per RECIST version 1.1 according to BICR assessment (Phase 3 only)</measure>
    <time_frame>36 months</time_frame>
    <description>DOR is defined as the time from first documentation of objective response of CR or PR to the first documentation of disease progression or death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DCR per RECIST version 1.1 according to BICR assessment (Phase 3 only)</measure>
    <time_frame>36 months</time_frame>
    <description>DCR is defined as subjects with CR, PR, or stable disease (SD or non-CR/non-progressive disease)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of AEs (Phase 3 only)</measure>
    <time_frame>36 months</time_frame>
    <description>An adverse event is any untoward medical occurrence in a subject or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of laboratory abnormalities (Phase 3 only)</measure>
    <time_frame>36 months</time_frame>
    <description>To be summarized using descriptive statistics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of dose modifications (Phase 3 only)</measure>
    <time_frame>36 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS per RECIST version 1.1 according to investigator assessment (Phase 2 only)</measure>
    <time_frame>18 months</time_frame>
    <description>PFS is defined as the time from the date of treatment initiation to the date of disease progression or death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration-time curve (AUC) to the time of the last quantifiable concentration (AUClast) of tucatinib (Phase 2 only)</measure>
    <time_frame>1 month</time_frame>
    <description>Pharmacokinetic (PK) parameter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC to AUClast of paclitaxel (Phase 2 only)</measure>
    <time_frame>1 month</time_frame>
    <description>PK parameter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum observed concentration (Cmax) of tucatinib (Phase 2 only)</measure>
    <time_frame>1 month</time_frame>
    <description>PK parameter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax of paclitaxel (Phase 2 only)</measure>
    <time_frame>1 month</time_frame>
    <description>PK parameter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of Cmax (Tmax) of tucatinib (Phase 2 only)</measure>
    <time_frame>1 month</time_frame>
    <description>PK parameter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax of paclitaxel (Phase 2 only)</measure>
    <time_frame>1 month</time_frame>
    <description>PK parameter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trough concentration (Ctrough) of tucatinib (Phase 2 only)</measure>
    <time_frame>18 months</time_frame>
    <description>PK parameter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ctrough of paclitaxel (Phase 2 only)</measure>
    <time_frame>18 months</time_frame>
    <description>PK parameter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Metabolic ratio of tucatinib based on AUC (MRAUC) (Phase 2 only)</measure>
    <time_frame>1 month</time_frame>
    <description>PK parameter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRAUC of paclitaxel (Phase 2 only)</measure>
    <time_frame>1 month</time_frame>
    <description>PK parameter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to deterioration of GEC symptoms as assessed by the European Organisation for Research and Treatment or Cancer (EORTC) quality of life questionnaire (QLQ)-C30 and EORTC QLQ-OG25 questionnaires.</measure>
    <time_frame>36 months</time_frame>
    <description>The EORTC questionnaires measure aspects of health-related quality of life (HRQoL). Time to deterioration will be assessed in specific pre-specified single items from either the EORTC QLQ-C30 or EORTC QLQ OG25 and deterioration is defined as a 10-point increase from baseline in the symptom scales and a 10-point decrease from baseline for overall HRQoL.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in health-related quality of life (HRQoL)</measure>
    <time_frame>36 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Utility index values as assessed by the EQ-5D-5L</measure>
    <time_frame>36 months</time_frame>
    <description>The EQ-5D-5L questionnaire is used as a preference based measurement of HRQoL outcomes. Data will be summarized using descriptive statistics.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">17</enrollment>
  <condition>Gastric Adenocarcinoma</condition>
  <condition>Gastroesophageal Junction Adenocarcinoma</condition>
  <condition>Esophageal Adenocarcinoma</condition>
  <arm_group>
    <arm_group_label>Phase 2 Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tucatinib + trastuzumab + ramucirumab + paclitaxel</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 3A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tucatinib + trastuzumab + ramucirumab + paclitaxel</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 3B</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ramucirumab + paclitaxel + tucatinib placebo + trastuzumab placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 3C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tucatinib + ramucirumab + paclitaxel + trastuzumab placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>tucatinib</intervention_name>
    <description>300 mg given twice daily orally</description>
    <arm_group_label>Arm 3A</arm_group_label>
    <arm_group_label>Arm 3C</arm_group_label>
    <arm_group_label>Phase 2 Arm</arm_group_label>
    <other_name>TUKYSA, ONT-380, ARRY-380</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>trastuzumab</intervention_name>
    <description>6 mg/kg loading dose will be administered intravenously (IV; into the vein) on Cycle 1 Day 1, followed by 4 mg/kg IV on Cycle 1 Day 15 and then Days 1 and 15 of each cycle thereafter</description>
    <arm_group_label>Arm 3A</arm_group_label>
    <arm_group_label>Phase 2 Arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ramucirumab</intervention_name>
    <description>8 mg/kg will be administered IV on Days 1 and 15 of each cycle</description>
    <arm_group_label>Arm 3A</arm_group_label>
    <arm_group_label>Arm 3B</arm_group_label>
    <arm_group_label>Arm 3C</arm_group_label>
    <arm_group_label>Phase 2 Arm</arm_group_label>
    <other_name>CYRAMZA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>paclitaxel</intervention_name>
    <description>60 or 80 mg/m^2 IV on Days 1, 8, and 15 of each cycle</description>
    <arm_group_label>Arm 3A</arm_group_label>
    <arm_group_label>Arm 3B</arm_group_label>
    <arm_group_label>Arm 3C</arm_group_label>
    <arm_group_label>Phase 2 Arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>tucatinib placebo</intervention_name>
    <description>Given twice daily orally</description>
    <arm_group_label>Arm 3B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>trastuzumab placebo</intervention_name>
    <description>IV on Days 1 and 15 of each cycle</description>
    <arm_group_label>Arm 3B</arm_group_label>
    <arm_group_label>Arm 3C</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically or cytologically confirmed diagnosis of locally-advanced unresectable&#xD;
             or metastatic HER2+ gastric or gastroesophageal junction adenocarcinoma (GEC)&#xD;
&#xD;
          -  HER2+ disease documented since progression of the most recent line of systemic&#xD;
             therapy, as follows:&#xD;
&#xD;
               -  Phase 2 paclitaxel dose optimization stage:&#xD;
&#xD;
                    -  HER2 amplification in a blood-based NGS assay performed at a central&#xD;
                       laboratory, or&#xD;
&#xD;
                    -  HER2 overexpression/amplification immunohistochemistry (IHC) and in situ&#xD;
                       hybridization (ISH) (IHC3+ or IHC2+/ISH+) assay of a tumor tissue sample&#xD;
&#xD;
               -  Phase 2 dose expansion stage:&#xD;
&#xD;
                    -  Cohort 2A: HER2 amplification in a blood-based NGS assay performed at a&#xD;
                       central laboratory&#xD;
&#xD;
                    -  Cohort 2B: No HER2 amplification by blood-based NGS assay, but HER2&#xD;
                       overexpression/amplification by IHC and ISH (IHC3+ or IHC2+/ISH+) assay of a&#xD;
                       tumor tissue sample&#xD;
&#xD;
               -  Phase 3: HER2 amplification in a blood-based NGS assay performed at a central&#xD;
                  laboratory&#xD;
&#xD;
          -  History of prior treatment with a HER2-directed antibody&#xD;
&#xD;
          -  Progressive disease during or after first-line therapy for locally-advanced&#xD;
             unresectable or metastatic GEC&#xD;
&#xD;
          -  Phase 2: Measurable disease according to RECIST version 1.1&#xD;
&#xD;
          -  Phase 3: Measurable or non-measurable disease according to RECIST version 1.1&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1&#xD;
&#xD;
          -  Life expectancy of at least 3 months, in the opinion of the investigator&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with squamous cell or undifferentiated GEC&#xD;
&#xD;
          -  Having received more than 1 line of prior systemic therapy for locally-advanced&#xD;
             unresectable or metastatic disease&#xD;
&#xD;
          -  Having received taxanes ≤12 months prior to enrollment, prior treatment with&#xD;
             ramucirumab, or prior treatment with tucatinib, lapatinib, neratinib, afatinib, or any&#xD;
             other investigational anti-HER2 and/or anti-EGFR tyrosine kinase inhibitor, or with&#xD;
             T-DM1, T-Dxd, or any other HER2-directed antibody-drug conjugate&#xD;
&#xD;
          -  Phase 2 paclitaxel dose optimization stage only: history of prior partial or total&#xD;
             gastrectomy&#xD;
&#xD;
          -  Unable to swallow pills&#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>JoAl Mayor, PharmD, BCOP</last_name>
    <role>Study Director</role>
    <affiliation>Seagen Inc.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Michelle Ubowski, PharmD</last_name>
    <role>Study Director</role>
    <affiliation>Seagen Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alabama at Birmingham</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35249</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic Arizona</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arizona Cancer Center / University of Arizona</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85724</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City of Hope National Medical Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCLA Medical Center / David Geffen School of Medicine</name>
      <address>
        <city>Santa Monica</city>
        <state>California</state>
        <zip>90404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers - Aurora</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Centers of Colorado - Denver</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SCL Health - St. Mary's Hospital &amp; Medical Center</name>
      <address>
        <city>Grand Junction</city>
        <state>Colorado</state>
        <zip>81501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SCL Health Good Samaritan Medical Center Cancer Centers of Colorado</name>
      <address>
        <city>Lafayette</city>
        <state>Colorado</state>
        <zip>80026</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lutheran Medical Center - Cancer Centers of Colorado</name>
      <address>
        <city>Wheat Ridge</city>
        <state>Colorado</state>
        <zip>80033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lombardi Cancer Center / Georgetown University Medical Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Holden Comprehensive Cancer Center / University of Iowa</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Norton Cancer Institute</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40217</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Minnesota Oncology Hematology P.A.</name>
      <address>
        <city>Saint Paul</city>
        <state>Minnesota</state>
        <zip>55102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Cancer Centers of Nevada</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89169</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Roswell Park Cancer Institute</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic - Taussig Cancer Institute</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncology Associates of Oregon</name>
      <address>
        <city>Eugene</city>
        <state>Oregon</state>
        <zip>97401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania / Perelman Center for Advanced Medicine</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Allegheny General Hospital</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Tennessee</name>
      <address>
        <city>Knoxville</city>
        <state>Tennessee</state>
        <zip>37920</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tennessee Oncology-Nashville/Sarah Cannon Research Institute</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology - Baylor Sammons Cancer Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology - San Antonio Medical Center</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78217</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology - Tyler</name>
      <address>
        <city>Tyler</city>
        <state>Texas</state>
        <zip>75702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Huntsman Cancer Institute/University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwest Cancer Specialists, P.C.</name>
      <address>
        <city>Vancouver</city>
        <state>Washington</state>
        <zip>98684</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Central Coast Local Health District (Gosford and Wyong Hospitals)</name>
      <address>
        <city>Gosford</city>
        <zip>2250</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Austin Health</name>
      <address>
        <city>Heidelberg</city>
        <zip>63V6 63</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>London Regional Cancer Program, London Health Sciences Centre</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A 5W9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier de l'Universite de Montreal</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H2X 3E4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McGill University Department of Oncology / McGill University Health Centre</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H4A 3J1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dong-A University Hospital</name>
      <address>
        <city>Busan</city>
        <zip>49201</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kyungpook National University Chilgok Hospital</name>
      <address>
        <city>Daegu</city>
        <zip>41404</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Bundang Hospital</name>
      <address>
        <city>Seongnam-si</city>
        <zip>13605</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>03080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Severance Hospital, Yonsei University Health System</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asan Medical Center - Oncology</name>
      <address>
        <city>Seoul</city>
        <zip>05505</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samsung Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>06351</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ajou University Hospital</name>
      <address>
        <city>Suwon-si</city>
        <zip>16499</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaohsiung Medical University Hospital</name>
      <address>
        <city>Kaohsiung</city>
        <zip>807</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>10002</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taipei Veterans General Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>11217</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute UK</name>
      <address>
        <city>London</city>
        <zip>W3 0ER</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Christie NHS Foundation Trust</name>
      <address>
        <city>Manchester</city>
        <zip>M20 4BX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Canada</country>
    <country>Korea, Republic of</country>
    <country>Taiwan</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>July 31, 2020</study_first_submitted>
  <study_first_submitted_qc>July 31, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 5, 2020</study_first_posted>
  <last_update_submitted>August 28, 2023</last_update_submitted>
  <last_update_submitted_qc>August 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 29, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HER2+</keyword>
  <keyword>HER2-positive</keyword>
  <keyword>GEA</keyword>
  <keyword>GEC</keyword>
  <keyword>GEJ</keyword>
  <keyword>Seattle Genetics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenocarcinoma</mesh_term>
    <mesh_term>Esophageal 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>Trastuzumab</mesh_term>
    <mesh_term>Ramucirumab</mesh_term>
    <mesh_term>Tucatinib</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/NCT04499924
org study id: SGNTUC-022
nct id: NCT04499924
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study is being done to see if tucatinib with trastuzumab, ramucirumab and paclitaxel
      works better than ramucirumab and paclitaxel to treat HER2-positive (HER2+) cancer of the gut
      (stomach or gastroesophageal cancer). This study will also look at what side effects happen
      when participants take this combination of drugs. A side effect is anything the drug does
      other than treating cancer.

      Study treatment will be given in 28-day cycles.

      In the Phase 2 part of the trial, participants and their doctors will know what drugs are
      being given (open-label). In the Phase 3 part, the study is "blinded." This means that
      participants, their doctor, and the study sponsor will not know which drugs are being given.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Overall survival (OS) (Phase 3 only)
time frame: 60 months
description: OS is defined as the time from randomization to death due to any cause
measure: Progression-free survival (PFS) per Response evaluation criteria in solid tumors (RECIST) version 1.1 according to investigator assessment (Phase 3 only)
time frame: 36 months
description: PFS is defined as the time from randomization to the date of disease progression or death from any cause
measure: Incidence of dose-limiting toxicities (DLTs) (Phase 2 only)
time frame: During first cycle of treatment; up to one month
measure: Incidence of adverse events (AEs) (Phase 2 only)
time frame: 18 months
description: An adverse event is any untoward medical occurrence in a subject or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
measure: Incidence of laboratory abnormalities (Phase 2 only)
time frame: 18 months
description: To be summarized using descriptive statistics.
measure: Incidence of dose modifications (Phase 2 only)
time frame: 18 months
measure: Confirmed objective response rate (ORR) per RECIST version 1.1 according to investigator assessment (Phases 2 and 3)
time frame: 36 months
description: ORR is defined as the proportion of subjects with best overall response of CR or PR
measure: ORR per RECIST version 1.1 according to investigator assessment (Phases 2 and 3)
time frame: 36 months
description: ORR is defined as the proportion of subjects with best overall response of CR or PR
measure: Duration of response (DOR) per RECIST version 1.1 according to investigator assessment (Phases 2 and 3)
time frame: 36 months
description: DOR is defined as the time from first documentation of objective response of CR or PR to the first documentation of disease progression or death from any cause
measure: Disease control rate (DCR) per RECIST version 1.1 according to investigator assessment (Phases 2 and 3)
time frame: 36 months
description: DCR is defined as subjects with CR, PR, or stable disease (SD or non-CR/non-progressive disease)
measure: PFS per RECIST v1.1 according to blinded independent central review (BICR) assessment (Phase 3 only)
time frame: 36 months
description: PFS is defined as the time from randomization to the date of disease progression or death from any cause
measure: Confirmed ORR per RECIST version 1.1 according to BICR assessment (Phase 3 only)
time frame: 36 months
description: ORR is defined as the proportion of subjects with best overall response of CR or PR
measure: ORR per RECIST version 1.1 according to BICR assessment (Phase 3 only)
time frame: 36 months
description: ORR is defined as the proportion of subjects with best overall response of CR or PR
measure: DOR per RECIST version 1.1 according to BICR assessment (Phase 3 only)
time frame: 36 months
description: DOR is defined as the time from first documentation of objective response of CR or PR to the first documentation of disease progression or death from any cause
measure: DCR per RECIST version 1.1 according to BICR assessment (Phase 3 only)
time frame: 36 months
description: DCR is defined as subjects with CR, PR, or stable disease (SD or non-CR/non-progressive disease)
measure: Incidence of AEs (Phase 3 only)
time frame: 36 months
description: An adverse event is any untoward medical occurrence in a subject or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
measure: Incidence of laboratory abnormalities (Phase 3 only)
time frame: 36 months
description: To be summarized using descriptive statistics.
measure: Incidence of dose modifications (Phase 3 only)
time frame: 36 months
measure: PFS per RECIST version 1.1 according to investigator assessment (Phase 2 only)
time frame: 18 months
description: PFS is defined as the time from the date of treatment initiation to the date of disease progression or death from any cause
measure: Area under the plasma concentration-time curve (AUC) to the time of the last quantifiable concentration (AUClast) of tucatinib (Phase 2 only)
time frame: 1 month
description: Pharmacokinetic (PK) parameter
measure: AUC to AUClast of paclitaxel (Phase 2 only)
time frame: 1 month
description: PK parameter
measure: Maximum observed concentration (Cmax) of tucatinib (Phase 2 only)
time frame: 1 month
description: PK parameter
measure: Cmax of paclitaxel (Phase 2 only)
time frame: 1 month
description: PK parameter
measure: Time of Cmax (Tmax) of tucatinib (Phase 2 only)
time frame: 1 month
description: PK parameter
measure: Tmax of paclitaxel (Phase 2 only)
time frame: 1 month
description: PK parameter
measure: Trough concentration (Ctrough) of tucatinib (Phase 2 only)
time frame: 18 months
description: PK parameter
measure: Ctrough of paclitaxel (Phase 2 only)
time frame: 18 months
description: PK parameter
measure: Metabolic ratio of tucatinib based on AUC (MRAUC) (Phase 2 only)
time frame: 1 month
description: PK parameter
measure: MRAUC of paclitaxel (Phase 2 only)
time frame: 1 month
description: PK parameter
measure: Time to deterioration of GEC symptoms as assessed by the European Organisation for Research and Treatment or Cancer (EORTC) quality of life questionnaire (QLQ)-C30 and EORTC QLQ-OG25 questionnaires.
time frame: 36 months
description: The EORTC questionnaires measure aspects of health-related quality of life (HRQoL). Time to deterioration will be assessed in specific pre-specified single items from either the EORTC QLQ-C30 or EORTC QLQ OG25 and deterioration is defined as a 10-point increase from baseline in the symptom scales and a 10-point decrease from baseline for overall HRQoL.
measure: Change from baseline in health-related quality of life (HRQoL)
time frame: 36 months
measure: Utility index values as assessed by the EQ-5D-5L
time frame: 36 months
description: The EQ-5D-5L questionnaire is used as a preference based measurement of HRQoL outcomes. Data will be summarized using descriptive statistics.
arm group label: Phase 2 Arm
arm group type: Experimental
description: Tucatinib + trastuzumab + ramucirumab + paclitaxel
arm group label: Arm 3A
arm group type: Experimental
description: Tucatinib + trastuzumab + ramucirumab + paclitaxel
arm group label: Arm 3B
arm group type: Active Comparator
description: Ramucirumab + paclitaxel + tucatinib placebo + trastuzumab placebo
arm group label: Arm 3C
arm group type: Experimental
description: Tucatinib + ramucirumab + paclitaxel + trastuzumab placebo
intervention type: Drug
intervention name: tucatinib
description: 300 mg given twice daily orally
arm group label: Arm 3A
arm group label: Arm 3C
arm group label: Phase 2 Arm
other name: TUKYSA, ONT-380, ARRY-380
intervention type: Drug
intervention name: trastuzumab
description: 6 mg/kg loading dose will be administered intravenously (IV; into the vein) on Cycle 1 Day 1, followed by 4 mg/kg IV on Cycle 1 Day 15 and then Days 1 and 15 of each cycle thereafter
arm group label: Arm 3A
arm group label: Phase 2 Arm
intervention type: Drug
intervention name: ramucirumab
description: 8 mg/kg will be administered IV on Days 1 and 15 of each cycle
arm group label: Arm 3A
arm group label: Arm 3B
arm group label: Arm 3C
arm group label: Phase 2 Arm
other name: CYRAMZA
intervention type: Drug
intervention name: paclitaxel
description: 60 or 80 mg/m^2 IV on Days 1, 8, and 15 of each cycle
arm group label: Arm 3A
arm group label: Arm 3B
arm group label: Arm 3C
arm group label: Phase 2 Arm
intervention type: Other
intervention name: tucatinib placebo
description: Given twice daily orally
arm group label: Arm 3B
intervention type: Other
intervention name: trastuzumab placebo
description: IV on Days 1 and 15 of each cycle
arm group label: Arm 3B
arm group label: Arm 3C
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: JoAl Mayor, PharmD, BCOP
role: Study Director
affiliation: Seagen Inc.
last name: Michelle Ubowski, PharmD
role: Study Director
affiliation: Seagen Inc.
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country: Australia
country: Canada
country: Korea, Republic of
country: Taiwan
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Adenocarcinoma
mesh term: Esophageal Neoplasms
mesh term: Paclitaxel
mesh term: Trastuzumab
mesh term: Ramucirumab
mesh term: Tucatinib