<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/NCT04430738</url>
  </required_header>
  <id_info>
    <org_study_id>SGNTUC-024</org_study_id>
    <nct_id>NCT04430738</nct_id>
  </id_info>
  <brief_title>Tucatinib Plus Trastuzumab and Oxaliplatin-based Chemotherapy or Pembrolizumab-containing Combinations for HER2+ Gastrointestinal Cancers</brief_title>
  <official_title>A Phase 1b/2 Dose Escalation and Expansion Study of Tucatinib in Combination With Trastuzumab and Oxaliplatin-based Chemotherapy or Pembrolizumab-containing Combinations for HER2+ Gastrointestinal Cancers</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>No</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 trial studies tucatinib to find out if it is safe when given with trastuzumab and other&#xD;
      anti-cancer drugs (pembrolizumab, FOLFOX, and CAPOX). It will look at what side effects&#xD;
      happen when participants take this combination of drugs. A side effect is anything the drug&#xD;
      does other than treating cancer. It will also look at whether tucatinib works with these&#xD;
      drugs to treat certain types of cancer.&#xD;
&#xD;
      The participants in this trial have HER2-positive (HER2+) cancer in their gut, stomach,&#xD;
      intestines, or gallbladder (gastrointestinal cancer).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 15, 2020</start_date>
  <completion_date type="Anticipated">October 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">May 30, 2024</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of renal dose-limiting toxicities (DLTs) (Cohorts 1A and 1B)</measure>
    <time_frame>Up to one month; 2 cycles after receiving all study treatment (each cycle is 14 days)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of adverse events (AEs) (Cohorts 1C, 1D, 1E, 1F, 1G, 2A, and 2B)</measure>
    <time_frame>Up to approximately 12 months</time_frame>
    <description>An AE is defined as any untoward medical occurrence in a clinical investigational participant 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 (Cohorts 1C, 1D, 1E, 1F, 1G, 2A, and 2B)</measure>
    <time_frame>Up to approximately 12 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of DLTs (Cohorts 1C, 1D, 1E, 1F, and 1G)</measure>
    <time_frame>Up to approximately 12 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of dose alterations (Cohort 1D)</measure>
    <time_frame>Up to approximately 12 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of AEs (Cohorts 1A and 1B)</measure>
    <time_frame>Up to approximately 12 months</time_frame>
    <description>An AE is defined as any untoward medical occurrence in a clinical investigational participant 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 (Cohorts 1A and 1B)</measure>
    <time_frame>Up to approximately 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in glomerular filtration rate (GFR) from baseline through 2 cycles of combination therapy (Cohorts 1A and 1B)</measure>
    <time_frame>Up to approximately 6 weeks</time_frame>
    <description>To be summarized using descriptive statistics</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic (PK) parameter of tucatinib - AUClast (Cohorts 1A and 1B)</measure>
    <time_frame>Up to approximately 2.5 months; through predose of Cycle 2, Day 1 (each cycle is 14 days)</time_frame>
    <description>To be summarized using descriptive statistics</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameter of tucatinib - Cmax (Cohorts 1A and 1B)</measure>
    <time_frame>Up to approximately 2.5 months; through predose of Cycle 2, Day 1 (each cycle is 14 days)</time_frame>
    <description>To be summarized using descriptive statistics</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameter of tucatinib - Ctrough (Cohorts 1A, 1B, 1C, 1E, 1F, and 1G)</measure>
    <time_frame>Up to approximately 2.5 months; through predose of Cycle 6, Day 1</time_frame>
    <description>To be summarized using descriptive statistics</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameter of tucatinib - Tmax (Cohorts 1A and 1B)</measure>
    <time_frame>Up to approximately 2.5 months; through predose of Cycle 2, Day 1 (each cycle is 14 days)</time_frame>
    <description>To be summarized using descriptive statistics</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameter of oxaliplatin - AUClast (Cohorts 1A and 1B)</measure>
    <time_frame>Up to 15 days; through Cycle 2, Day 1 (each cycle is 14 days)</time_frame>
    <description>To be summarized using descriptive statistics</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameter of oxaliplatin - Cmax (Cohorts 1A and 1B)</measure>
    <time_frame>Up to 15 days; through Cycle 2, Day 1 (each cycle is 14 days)</time_frame>
    <description>To be summarized using descriptive statistics</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameter of oxaliplatin - Tmax (Cohorts 1A and 1B)</measure>
    <time_frame>Up to 15 days; through Cycle 2, Day 1 (each cycle is 14 days)</time_frame>
    <description>To be summarized using descriptive statistics</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Confirmed objective response rate (cORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 per investigator assessment (INV) (Cohort 2A)</measure>
    <time_frame>Up to approximately 2.5 years</time_frame>
    <description>cORR is defined as the proportion of participants with confirmed complete response (CR) or partial response (PR)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR) according to RECIST v1.1 per INV (Cohorts 1C, 1E, 1F, 1G, and 2A)</measure>
    <time_frame>Up to approximately 2.5 years</time_frame>
    <description>DOR is defined as the time from first documentation of objective response of confirmed CR or confirmed PR to the first documentation of disease progression or death from any cause, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS) according to RECIST v1.1 per INV (Cohorts 1C, 1E, 1F, 1G, and 2A)</measure>
    <time_frame>Up to approximately 2.5 years</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, which occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS) (Cohort 1C, 1E, 1F, 1G, and 2A)</measure>
    <time_frame>Up to approximately 2.5 years</time_frame>
    <description>OS is defined as the time from treatment initiation to death due to any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR) (Cohorts 1C, 1E, 1F, and 1G)</measure>
    <time_frame>Up to approximately 2.5 years</time_frame>
    <description>ORR is defined as the proportion of subjects with confirmed CR or PR, according to RECIST v1.1.</description>
  </secondary_outcome>
  <number_of_arms>9</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Colorectal Carcinoma</condition>
  <condition>Gastric Adenocarcinoma</condition>
  <condition>GEJ Adenocarcinoma</condition>
  <condition>Esophageal Adenocarcinoma</condition>
  <condition>Cholangiocarcinoma</condition>
  <condition>Gallbladder Carcinoma</condition>
  <arm_group>
    <arm_group_label>Cohort 1A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tucatinib + trastuzumab + FOLFOX given in 14-day cycles</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 1B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tucatinib + trastuzumab + FOLFOX given in 14-day cycles</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 1C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tucatinib + trastuzumab + CAPOX given in 21-day cycles</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 1D</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tucatinib + trastuzumab + FOLFOX. Tucatinib and FOLFOX given in 14-day cycles and trastuzumab given every 21 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 1E</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tucatinib + trastuzumab + pembrolizumab + FOLFOX. Tucatinib and FOLFOX given in 14-day cycles, trastuzumab given in 21-day cycles, and pembrolizumab given in 42-day cycles</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 1F</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tucatinib + trastuzumab + pembrolizumab + CAPOX. Tucatinib, trastuzumab, and CAPOX given in 21-day cycles and pembrolizumab given in 42-day cycles.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 1G</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tucatinib + trastuzumab + pembrolizumab. Tucatinib and trastuzumab given in 21-day cycles and pembrolizumab given in 42-day cycles.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tucatinib + trastuzumab + pembrolizumab + (FOLFOX or CAPOX). Either (1) tucatinib and FOLFOX given in 14-day cycles or (2) tucatinib and CAPOX given in 21-day cycles. Trastuzumab given in 21-day cycles and pembrolizumab given in 42-day cycles.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tucatinib + trastuzumab + FOLFOX given in 14-day cycles.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>tucatinib</intervention_name>
    <description>For Cohort 1A, 150 mg will be administered twice daily by mouth (orally) from Cycle 1 Day 8 onwards. For all other cohorts, 300 mg (or intermediate dose) will be given orally twice daily starting on Cycle 1 Day 1.</description>
    <arm_group_label>Cohort 1A</arm_group_label>
    <arm_group_label>Cohort 1B</arm_group_label>
    <arm_group_label>Cohort 1C</arm_group_label>
    <arm_group_label>Cohort 1D</arm_group_label>
    <arm_group_label>Cohort 1E</arm_group_label>
    <arm_group_label>Cohort 1F</arm_group_label>
    <arm_group_label>Cohort 1G</arm_group_label>
    <arm_group_label>Cohort 2A</arm_group_label>
    <arm_group_label>Cohort 2B</arm_group_label>
    <other_name>TUKYSA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>trastuzumab</intervention_name>
    <description>Cohorts 1A and 1B: a 6 mg/kg loading dose will be given into the vein (IV; intravenously) on Cycle 1 Day 1, followed by a dose of 4 mg/kg IV every 2 weeks starting on Cycle 2 Day 1. Cohorts 1C, 1D, 1E, 1F, 1G, 2A, and 2B: an 8 mg/kg loading dose will be administered IV on Cycle 1 Day 1, followed by a dose of 6 mg/kg IV every 3 weeks thereafter.</description>
    <arm_group_label>Cohort 1A</arm_group_label>
    <arm_group_label>Cohort 1B</arm_group_label>
    <arm_group_label>Cohort 1C</arm_group_label>
    <arm_group_label>Cohort 1D</arm_group_label>
    <arm_group_label>Cohort 1E</arm_group_label>
    <arm_group_label>Cohort 1F</arm_group_label>
    <arm_group_label>Cohort 1G</arm_group_label>
    <arm_group_label>Cohort 2A</arm_group_label>
    <arm_group_label>Cohort 2B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>oxaliplatin</intervention_name>
    <description>85 mg/m^2 given IV every 2 weeks for cohorts using FOLFOX. For cohorts using CAPOX regimen, 130 mg/m^2 given every 3 weeks.</description>
    <arm_group_label>Cohort 1A</arm_group_label>
    <arm_group_label>Cohort 1B</arm_group_label>
    <arm_group_label>Cohort 1C</arm_group_label>
    <arm_group_label>Cohort 1D</arm_group_label>
    <arm_group_label>Cohort 1E</arm_group_label>
    <arm_group_label>Cohort 1F</arm_group_label>
    <arm_group_label>Cohort 2A</arm_group_label>
    <arm_group_label>Cohort 2B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>leucovorin</intervention_name>
    <description>200 (mFOLFOX7) or 400 (mFOLFOX6) mg/m^2 given IV every 2 weeks. Part of FOLFOX regimen.</description>
    <arm_group_label>Cohort 1A</arm_group_label>
    <arm_group_label>Cohort 1B</arm_group_label>
    <arm_group_label>Cohort 1D</arm_group_label>
    <arm_group_label>Cohort 1E</arm_group_label>
    <arm_group_label>Cohort 2A</arm_group_label>
    <arm_group_label>Cohort 2B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>fluorouracil</intervention_name>
    <description>400 mg/m^2 (IV bolus after leucovorin) and/or 2400 mg/m^2 (continuous infusion over 46 hours). Part of FOLFOX regimen.</description>
    <arm_group_label>Cohort 1A</arm_group_label>
    <arm_group_label>Cohort 1B</arm_group_label>
    <arm_group_label>Cohort 1D</arm_group_label>
    <arm_group_label>Cohort 1E</arm_group_label>
    <arm_group_label>Cohort 2A</arm_group_label>
    <arm_group_label>Cohort 2B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>capecitabine</intervention_name>
    <description>1000 mg/m^2 is taken twice per day orally on Days 1-14 of each 3 week cycle. Part of CAPOX regimen.</description>
    <arm_group_label>Cohort 1C</arm_group_label>
    <arm_group_label>Cohort 1F</arm_group_label>
    <arm_group_label>Cohort 2A</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>pembrolizumab</intervention_name>
    <description>400 mg given by IV on day 1 of cycle 1, then every 6 weeks.</description>
    <arm_group_label>Cohort 1E</arm_group_label>
    <arm_group_label>Cohort 1F</arm_group_label>
    <arm_group_label>Cohort 1G</arm_group_label>
    <arm_group_label>Cohort 2A</arm_group_label>
    <other_name>KEYTRUDA</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants must have an unresectable or metastatic solid malignancy that is&#xD;
             histologically or cytologically confirmed to be one of the tumor types listed below:&#xD;
&#xD;
               -  Cohorts 1A, 1B, 1C, and 1D&#xD;
&#xD;
                    -  CRC&#xD;
&#xD;
                    -  Gastric adenocarcinoma&#xD;
&#xD;
                    -  GEJ adenocarcinoma&#xD;
&#xD;
                    -  Esophageal adenocarcinoma&#xD;
&#xD;
                    -  Cholangiocarcinoma&#xD;
&#xD;
                    -  Gallbladder carcinoma&#xD;
&#xD;
               -  Cohorts 1E, 1F, 1G, and 2A&#xD;
&#xD;
                    -  Gastric adenocarcinoma&#xD;
&#xD;
                    -  GEJ adenocarcinoma&#xD;
&#xD;
                    -  Esophageal adenocarcinoma&#xD;
&#xD;
               -  Cohort 2B&#xD;
&#xD;
                    -  CRC&#xD;
&#xD;
          -  Participants must be candidates to receive an oxaliplatin-based regimen as part of&#xD;
             their standard-of-care treatment for all cohorts, except Cohort 1G.&#xD;
&#xD;
          -  HER2+ disease, as determined by historic or local laboratory testing&#xD;
&#xD;
          -  Phase 1b cohorts: measurable or non-measurable disease according to RECIST v1.1 as&#xD;
             determined by the investigator&#xD;
&#xD;
          -  Phase 2 cohorts: measurable disease according to RECIST v1.1 as determined by the&#xD;
             investigator&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group Performance Status score of 0 or 1.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of known hypersensitivity to planned study treatment&#xD;
&#xD;
          -  Known to be positive for Hepatitis B or C&#xD;
&#xD;
          -  For Cohorts 2A and 2B: prior anti-HER2 therapies&#xD;
&#xD;
          -  For Cohorts 1E, 1F, 1G, 2A: Prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2&#xD;
             agent or with an agent directed to another stimulatory or co-inhibitory T-cell&#xD;
             receptor (eg, CTLA-4, OX 40, CD137), and was discontinued from that treatment due to a&#xD;
             Grade 3 or higher immune-related adverse event (irAE)&#xD;
&#xD;
        There are additional inclusion criteria. The study center will determine if criteria for&#xD;
        participations are met.&#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>
  <overall_contact>
    <last_name>Seagen Trial Information Support</last_name>
    <phone>8663337436</phone>
    <email>clinicaltrials@seagen.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Mayo Clinic Arizona</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85054</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Stanford Cancer Center / Blood and Marrow Transplant Program</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>University of Colorado Hospital / University of Colorado</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </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>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins Medical Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20016</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Carol Goldener, RN</last_name>
      <phone>220-660-6500</phone>
      <email>cgolden9@jhmi.edu</email>
    </contact>
    <investigator>
      <last_name>Michael Pishvaian</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>H. Lee Moffitt Cancer Center and Research Institute</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>University of Chicago Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637-1470</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55903-4008</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Washington University in St Louis</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jordan Wynn</last_name>
      <phone>314-273-4913</phone>
      <email>wynn@wustl.edu</email>
    </contact>
    <investigator>
      <last_name>Patrick Grierson</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>New Mexico Cancer Center</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87131</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Erika Maestas, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Levine Cancer Institute</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28204</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Melani Terry</last_name>
      <phone>980-442-2000</phone>
      <email>Melani.terry@atriumhealth.org</email>
    </contact>
    <investigator>
      <last_name>Mohamed E Salem, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </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>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Gabrail Cancer Center Research, LLC</name>
      <address>
        <city>Canton</city>
        <state>Ohio</state>
        <zip>44718</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic, The</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Seattle Cancer Care Alliance / University of Washington</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109-1023</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Madilyn Heit</last_name>
      <phone>206-606-6387</phone>
      <email>mheit@seattlecca.org</email>
    </contact>
    <investigator>
      <last_name>David B Zhen</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>National Cancer Center Hospital</name>
      <address>
        <city>Chuo-ku</city>
        <state>Other</state>
        <zip>104-0045</zip>
        <country>Japan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Hidekazu Hirano, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>National Cancer Center Hospital East</name>
      <address>
        <city>Kashiwa-shi</city>
        <state>Other</state>
        <zip>277-8577</zip>
        <country>Japan</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>St. Marianna University School of Medicine</name>
      <address>
        <city>Kawasaki-shi</city>
        <state>Other</state>
        <zip>2168511</zip>
        <country>Japan</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>The Cancer Institute Hospital of Japanese Foundation for Cancer Research</name>
      <address>
        <city>Koto-ku</city>
        <state>Other</state>
        <zip>135-8550</zip>
        <country>Japan</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Aichi Cancer Center</name>
      <address>
        <city>Nagoya-shi</city>
        <state>Other</state>
        <zip>464-8681</zip>
        <country>Japan</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Kindai University Hospital</name>
      <address>
        <city>Osakasayama-Shi</city>
        <state>Other</state>
        <zip>589-8511</zip>
        <country>Japan</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Osaka International Cancer Institute</name>
      <address>
        <city>Osaka</city>
        <state>Other</state>
        <zip>541-8567</zip>
        <country>Japan</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location_countries>
    <country>Japan</country>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>June 10, 2020</study_first_submitted>
  <study_first_submitted_qc>June 11, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 12, 2020</study_first_posted>
  <last_update_submitted>September 8, 2023</last_update_submitted>
  <last_update_submitted_qc>September 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HER2+</keyword>
  <keyword>HER2-positive</keyword>
  <keyword>CRC</keyword>
  <keyword>Gastric cancer</keyword>
  <keyword>Esophageal cancer</keyword>
  <keyword>Seattle Genetics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Adenocarcinoma</mesh_term>
    <mesh_term>Cholangiocarcinoma</mesh_term>
    <mesh_term>Colorectal Neoplasms</mesh_term>
    <mesh_term>Gastrointestinal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leucovorin</mesh_term>
    <mesh_term>Pembrolizumab</mesh_term>
    <mesh_term>Trastuzumab</mesh_term>
    <mesh_term>Fluorouracil</mesh_term>
    <mesh_term>Capecitabine</mesh_term>
    <mesh_term>Oxaliplatin</mesh_term>
    <mesh_term>Tucatinib</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/NCT04430738
org study id: SGNTUC-024
nct id: NCT04430738
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This trial studies tucatinib to find out if it is safe when given with trastuzumab and other
      anti-cancer drugs (pembrolizumab, FOLFOX, and CAPOX). It will 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. It will also look at whether tucatinib works with these
      drugs to treat certain types of cancer.

      The participants in this trial have HER2-positive (HER2+) cancer in their gut, stomach,
      intestines, or gallbladder (gastrointestinal cancer).
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of renal dose-limiting toxicities (DLTs) (Cohorts 1A and 1B)
time frame: Up to one month; 2 cycles after receiving all study treatment (each cycle is 14 days)
measure: Incidence of adverse events (AEs) (Cohorts 1C, 1D, 1E, 1F, 1G, 2A, and 2B)
time frame: Up to approximately 12 months
description: An AE is defined as any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
measure: Incidence of laboratory abnormalities (Cohorts 1C, 1D, 1E, 1F, 1G, 2A, and 2B)
time frame: Up to approximately 12 months
measure: Incidence of DLTs (Cohorts 1C, 1D, 1E, 1F, and 1G)
time frame: Up to approximately 12 months
measure: Incidence of dose alterations (Cohort 1D)
time frame: Up to approximately 12 months
measure: Incidence of AEs (Cohorts 1A and 1B)
time frame: Up to approximately 12 months
description: An AE is defined as any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
measure: Incidence of laboratory abnormalities (Cohorts 1A and 1B)
time frame: Up to approximately 12 months
measure: Change in glomerular filtration rate (GFR) from baseline through 2 cycles of combination therapy (Cohorts 1A and 1B)
time frame: Up to approximately 6 weeks
description: To be summarized using descriptive statistics
measure: Pharmacokinetic (PK) parameter of tucatinib - AUClast (Cohorts 1A and 1B)
time frame: Up to approximately 2.5 months; through predose of Cycle 2, Day 1 (each cycle is 14 days)
description: To be summarized using descriptive statistics
measure: PK parameter of tucatinib - Cmax (Cohorts 1A and 1B)
time frame: Up to approximately 2.5 months; through predose of Cycle 2, Day 1 (each cycle is 14 days)
description: To be summarized using descriptive statistics
measure: PK parameter of tucatinib - Ctrough (Cohorts 1A, 1B, 1C, 1E, 1F, and 1G)
time frame: Up to approximately 2.5 months; through predose of Cycle 6, Day 1
description: To be summarized using descriptive statistics
measure: PK parameter of tucatinib - Tmax (Cohorts 1A and 1B)
time frame: Up to approximately 2.5 months; through predose of Cycle 2, Day 1 (each cycle is 14 days)
description: To be summarized using descriptive statistics
measure: PK parameter of oxaliplatin - AUClast (Cohorts 1A and 1B)
time frame: Up to 15 days; through Cycle 2, Day 1 (each cycle is 14 days)
description: To be summarized using descriptive statistics
measure: PK parameter of oxaliplatin - Cmax (Cohorts 1A and 1B)
time frame: Up to 15 days; through Cycle 2, Day 1 (each cycle is 14 days)
description: To be summarized using descriptive statistics
measure: PK parameter of oxaliplatin - Tmax (Cohorts 1A and 1B)
time frame: Up to 15 days; through Cycle 2, Day 1 (each cycle is 14 days)
description: To be summarized using descriptive statistics
measure: Confirmed objective response rate (cORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 per investigator assessment (INV) (Cohort 2A)
time frame: Up to approximately 2.5 years
description: cORR is defined as the proportion of participants with confirmed complete response (CR) or partial response (PR)
measure: Duration of response (DOR) according to RECIST v1.1 per INV (Cohorts 1C, 1E, 1F, 1G, and 2A)
time frame: Up to approximately 2.5 years
description: DOR is defined as the time from first documentation of objective response of confirmed CR or confirmed PR to the first documentation of disease progression or death from any cause, whichever occurs first.
measure: Progression-free survival (PFS) according to RECIST v1.1 per INV (Cohorts 1C, 1E, 1F, 1G, and 2A)
time frame: Up to approximately 2.5 years
description: PFS is defined as the time from the date of treatment initiation to the date of disease progression or death from any cause, which occurs first.
measure: Overall survival (OS) (Cohort 1C, 1E, 1F, 1G, and 2A)
time frame: Up to approximately 2.5 years
description: OS is defined as the time from treatment initiation to death due to any cause
measure: Objective response rate (ORR) (Cohorts 1C, 1E, 1F, and 1G)
time frame: Up to approximately 2.5 years
description: ORR is defined as the proportion of subjects with confirmed CR or PR, according to RECIST v1.1.
arm group label: Cohort 1A
arm group type: Experimental
description: Tucatinib + trastuzumab + FOLFOX given in 14-day cycles
arm group label: Cohort 1B
arm group type: Experimental
description: Tucatinib + trastuzumab + FOLFOX given in 14-day cycles
arm group label: Cohort 1C
arm group type: Experimental
description: Tucatinib + trastuzumab + CAPOX given in 21-day cycles
arm group label: Cohort 1D
arm group type: Experimental
description: Tucatinib + trastuzumab + FOLFOX. Tucatinib and FOLFOX given in 14-day cycles and trastuzumab given every 21 days
arm group label: Cohort 1E
arm group type: Experimental
description: Tucatinib + trastuzumab + pembrolizumab + FOLFOX. Tucatinib and FOLFOX given in 14-day cycles, trastuzumab given in 21-day cycles, and pembrolizumab given in 42-day cycles
arm group label: Cohort 1F
arm group type: Experimental
description: Tucatinib + trastuzumab + pembrolizumab + CAPOX. Tucatinib, trastuzumab, and CAPOX given in 21-day cycles and pembrolizumab given in 42-day cycles.
arm group label: Cohort 1G
arm group type: Experimental
description: Tucatinib + trastuzumab + pembrolizumab. Tucatinib and trastuzumab given in 21-day cycles and pembrolizumab given in 42-day cycles.
arm group label: Cohort 2A
arm group type: Experimental
description: Tucatinib + trastuzumab + pembrolizumab + (FOLFOX or CAPOX). Either (1) tucatinib and FOLFOX given in 14-day cycles or (2) tucatinib and CAPOX given in 21-day cycles. Trastuzumab given in 21-day cycles and pembrolizumab given in 42-day cycles.
arm group label: Cohort 2B
arm group type: Experimental
description: Tucatinib + trastuzumab + FOLFOX given in 14-day cycles.
intervention type: Drug
intervention name: tucatinib
description: For Cohort 1A, 150 mg will be administered twice daily by mouth (orally) from Cycle 1 Day 8 onwards. For all other cohorts, 300 mg (or intermediate dose) will be given orally twice daily starting on Cycle 1 Day 1.
arm group label: Cohort 1A
arm group label: Cohort 1B
arm group label: Cohort 1C
arm group label: Cohort 1D
arm group label: Cohort 1E
arm group label: Cohort 1F
arm group label: Cohort 1G
arm group label: Cohort 2A
arm group label: Cohort 2B
other name: TUKYSA
intervention type: Drug
intervention name: trastuzumab
description: Cohorts 1A and 1B: a 6 mg/kg loading dose will be given into the vein (IV; intravenously) on Cycle 1 Day 1, followed by a dose of 4 mg/kg IV every 2 weeks starting on Cycle 2 Day 1. Cohorts 1C, 1D, 1E, 1F, 1G, 2A, and 2B: an 8 mg/kg loading dose will be administered IV on Cycle 1 Day 1, followed by a dose of 6 mg/kg IV every 3 weeks thereafter.
arm group label: Cohort 1A
arm group label: Cohort 1B
arm group label: Cohort 1C
arm group label: Cohort 1D
arm group label: Cohort 1E
arm group label: Cohort 1F
arm group label: Cohort 1G
arm group label: Cohort 2A
arm group label: Cohort 2B
intervention type: Drug
intervention name: oxaliplatin
description: 85 mg/m^2 given IV every 2 weeks for cohorts using FOLFOX. For cohorts using CAPOX regimen, 130 mg/m^2 given every 3 weeks.
arm group label: Cohort 1A
arm group label: Cohort 1B
arm group label: Cohort 1C
arm group label: Cohort 1D
arm group label: Cohort 1E
arm group label: Cohort 1F
arm group label: Cohort 2A
arm group label: Cohort 2B
intervention type: Drug
intervention name: leucovorin
description: 200 (mFOLFOX7) or 400 (mFOLFOX6) mg/m^2 given IV every 2 weeks. Part of FOLFOX regimen.
arm group label: Cohort 1A
arm group label: Cohort 1B
arm group label: Cohort 1D
arm group label: Cohort 1E
arm group label: Cohort 2A
arm group label: Cohort 2B
intervention type: Drug
intervention name: fluorouracil
description: 400 mg/m^2 (IV bolus after leucovorin) and/or 2400 mg/m^2 (continuous infusion over 46 hours). Part of FOLFOX regimen.
arm group label: Cohort 1A
arm group label: Cohort 1B
arm group label: Cohort 1D
arm group label: Cohort 1E
arm group label: Cohort 2A
arm group label: Cohort 2B
intervention type: Drug
intervention name: capecitabine
description: 1000 mg/m^2 is taken twice per day orally on Days 1-14 of each 3 week cycle. Part of CAPOX regimen.
arm group label: Cohort 1C
arm group label: Cohort 1F
arm group label: Cohort 2A
intervention type: Drug
intervention name: pembrolizumab
description: 400 mg given by IV on day 1 of cycle 1, then every 6 weeks.
arm group label: Cohort 1E
arm group label: Cohort 1F
arm group label: Cohort 1G
arm group label: Cohort 2A
other name: KEYTRUDA
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.
last name: Seagen Trial Information Support
phone: 8663337436
email: clinicaltrials@seagen.com
facility: 
status: Active, not recruiting
facility: 
status: Completed
facility: 
status: Active, not recruiting
facility: 
status: Completed
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Completed
facility: 
status: Completed
facility: 
status: Completed
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Active, not recruiting
facility: 
status: Completed
facility: 
status: Active, not recruiting
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
country: Japan
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Adenocarcinoma
mesh term: Cholangiocarcinoma
mesh term: Colorectal Neoplasms
mesh term: Gastrointestinal Neoplasms
mesh term: Leucovorin
mesh term: Pembrolizumab
mesh term: Trastuzumab
mesh term: Fluorouracil
mesh term: Capecitabine
mesh term: Oxaliplatin
mesh term: Tucatinib
sharing ipd: No