<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/NCT03786081</url>
  </required_header>
  <id_info>
    <org_study_id>GCT1015-05</org_study_id>
    <secondary_id>InnovaTV 205</secondary_id>
    <secondary_id>MK3475 KN 834</secondary_id>
    <secondary_id>ENGOT-cx8</secondary_id>
    <secondary_id>GOG-3024</secondary_id>
    <nct_id>NCT03786081</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of Tisotumab Vedotin Monotherapy &amp; in Combination With Other Cancer Agents in Subjects With Cervical Cancer</brief_title>
  <official_title>A Phase 1b/2 Open-Label Trial of Tisotumab Vedotin (HuMax®-TF-ADC) Monotherapy and in Combination With Other Agents in Subjects With Recurrent or Stage IVB Cervical Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Seagen Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Genmab</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>European Network of Gynaecological Oncological Trial Groups (ENGOT)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Belgian Gynaecological Oncology Group</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Gynecologic Oncology Group</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </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 is an open label, multi-center trial of tisotumab vedotin monotherapy and in combination&#xD;
      with bevacizumab, pembrolizumab, or carboplatin in subjects with recurrent or stage IVB&#xD;
      cervical cancer.&#xD;
&#xD;
      The trial consists of two-parts a dose escalation part and an expansion part. The expansion&#xD;
      part of the trial will be initiated once the Recommended Phase 2 Dose (RP2D) of the&#xD;
      combinations have been determined in the dose escalation part.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The dose escalation part will occur in participants with cervical cancer who have progressed&#xD;
      during or after standard of care therapy and who are intolerant or ineligible to receive&#xD;
      standard of care treatments. Arm A will be conducted by escalating doses of both tisotumab&#xD;
      vedotin and bevacizumab. Dose escalations of the tisotumab vedotin + pembrolizumab and&#xD;
      tisotumab vedotin + carboplatin combinations (Arms B and C, respectively) will be conducted&#xD;
      by combining fixed doses of either pembrolizumab or carboplatin with increasing doses of&#xD;
      tisotumab vedotin.&#xD;
&#xD;
      The dose expansion part of this study (Arms D through H) will be conducted in 2 populations:&#xD;
      participants with cervical cancer who have not received prior systemic therapy for recurrent&#xD;
      or stage IVB cervical cancer (Arms D, E, and H) and participants with cervical cancer who&#xD;
      have progressed on or after at least 1 but no more than 2 prior systemic therapies (Arms F&#xD;
      and G).&#xD;
&#xD;
      Participants enrolled to Arms D, E, F and H will receive the RP2D of tisotumab vedotin&#xD;
      established in the dose escalation part. Participants enrolled to Arm G will receive&#xD;
      tisotumab vedotin weekly (at a dose lower than subjects in all other Arms) for three weeks&#xD;
      and 1 week off (28-day treatment cycle).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">February 27, 2019</start_date>
  <completion_date type="Anticipated">September 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">September 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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Dose escalation: Dose Limiting Toxicities (DLTs)</measure>
    <time_frame>DLTs will be identified during the first treatment cycle (21 day cycles)</time_frame>
    <description>To establish the MTD and RP2D of tisotumab vedotin in combination</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Dose expansion: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)</measure>
    <time_frame>approximately 2 years</time_frame>
    <description>Objective response is defined as confirmed partial response (PR) or complete response (CR)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of adverse events (AEs)</measure>
    <time_frame>up to 2 years</time_frame>
    <description>Any untoward medical occurrence in a clinical trial participant whether or not considered related to the medicinal product.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose escalation: ORR per RECIST v1.1</measure>
    <time_frame>approximately 2 years</time_frame>
    <description>Objective response is defined as confirmed PR or CR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR) per RECIST v1.1 by investigator assessment</measure>
    <time_frame>approximately 2 years</time_frame>
    <description>Will be calculated from the date of initial documentation of a response (CR or PR) to the date of first documented evidence of progressive disease (PD) or death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Response (TTR) per RECIST v1.1 by investigator assessment</measure>
    <time_frame>approximately 2 years</time_frame>
    <description>Will be calculated from the date of the first dose to the date of the initial documentation of response (CR or PR).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS) per RECIST v1.1 by investigator assessment</measure>
    <time_frame>approximately 2 years</time_frame>
    <description>The time from the date of the first trial drug administration to the date of the first documented disease progression or death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>approximately 2 years</time_frame>
    <description>The time from the date of the first trial drug administration to the date of death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum concentration (Cmax) (All Arms except G)</measure>
    <time_frame>Up to 42 days</time_frame>
    <description>Pharmacokinetic (PK) parameter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax (Arm G only)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>PK parameter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trough Concentration (Ctrough) (All Arms)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>PK parameter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve (AUC) (All Arms except G)</measure>
    <time_frame>Through 21 days after first dose</time_frame>
    <description>PK parameter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC (Arm G only)</measure>
    <time_frame>Through 8 days after first dose</time_frame>
    <description>PK parameter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anti-drug antibodies (ADAs)</measure>
    <time_frame>Up to 2 years</time_frame>
  </secondary_outcome>
  <number_of_arms>8</number_of_arms>
  <enrollment type="Actual">214</enrollment>
  <condition>Cervical Cancer</condition>
  <arm_group>
    <arm_group_label>A: Tisotumab Vedotin + bevacizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose escalation: Tisotumab vedotin in combination with bevacizumab once every three weeks in previously treated patients</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B: Tisotumab vedotin + pembrolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose escalation: Tisotumab vedotin in combination with pembrolizumab once every three weeks in previously treated patients</description>
  </arm_group>
  <arm_group>
    <arm_group_label>C: Tisotumab vedotin + carboplatin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose escalation: Tisotumab vedotin in combination with carboplatin once every three weeks in previously treated patients</description>
  </arm_group>
  <arm_group>
    <arm_group_label>D: Tisotumab vedotin + carboplatin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose expansion:Tisotumab vedotin in combination with carboplatin once every three weeks in previously untreated patients</description>
  </arm_group>
  <arm_group>
    <arm_group_label>E: Tisotumab vedotin + pembrolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose expansion: Tisotumab vedotin in combination with pembrolizumab once every three weeks in previously untreated patients</description>
  </arm_group>
  <arm_group>
    <arm_group_label>F: Tisotumab vedotin + pembrolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose expansion: Tisotumab vedotin in combination with pembrolizumab once every three weeks in previously treated patients</description>
  </arm_group>
  <arm_group>
    <arm_group_label>G: Tisotumab vedotin monotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose expansion: Tisotumab vedotin monotherapy weekly for three weeks and 1 week off (28 day treatment cycle) in previously treated patients.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>H: Tisotumab vedotin + pembrolizumab + carboplatin +/- bevacizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose expansion: Tisotumab vedotin in combination with pembrolizumab and carboplatin with or without bevacizumab once every three weeks in previously untreated patients</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tisotumab Vedotin</intervention_name>
    <description>Given into the vein (IV)</description>
    <arm_group_label>A: Tisotumab Vedotin + bevacizumab</arm_group_label>
    <arm_group_label>B: Tisotumab vedotin + pembrolizumab</arm_group_label>
    <arm_group_label>C: Tisotumab vedotin + carboplatin</arm_group_label>
    <arm_group_label>D: Tisotumab vedotin + carboplatin</arm_group_label>
    <arm_group_label>E: Tisotumab vedotin + pembrolizumab</arm_group_label>
    <arm_group_label>F: Tisotumab vedotin + pembrolizumab</arm_group_label>
    <arm_group_label>G: Tisotumab vedotin monotherapy</arm_group_label>
    <arm_group_label>H: Tisotumab vedotin + pembrolizumab + carboplatin +/- bevacizumab</arm_group_label>
    <other_name>TIVDAK</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bevacizumab</intervention_name>
    <description>Given via IV</description>
    <arm_group_label>A: Tisotumab Vedotin + bevacizumab</arm_group_label>
    <arm_group_label>H: Tisotumab vedotin + pembrolizumab + carboplatin +/- bevacizumab</arm_group_label>
    <other_name>Avastin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Given via IV</description>
    <arm_group_label>B: Tisotumab vedotin + pembrolizumab</arm_group_label>
    <arm_group_label>E: Tisotumab vedotin + pembrolizumab</arm_group_label>
    <arm_group_label>F: Tisotumab vedotin + pembrolizumab</arm_group_label>
    <arm_group_label>H: Tisotumab vedotin + pembrolizumab + carboplatin +/- bevacizumab</arm_group_label>
    <other_name>Keytruda</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>Given via IV</description>
    <arm_group_label>C: Tisotumab vedotin + carboplatin</arm_group_label>
    <arm_group_label>D: Tisotumab vedotin + carboplatin</arm_group_label>
    <arm_group_label>H: Tisotumab vedotin + pembrolizumab + carboplatin +/- bevacizumab</arm_group_label>
    <other_name>Paraplatin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Must have squamous, adenosquamous, or adenocarcinoma of the cervix and progressed on&#xD;
             or after standard of care treatments or are ineligible or intolerant to standard of&#xD;
             care for recurrent or stage IVB cervical cancer (Arms A, B and C only).&#xD;
&#xD;
          -  Must have squamous, adenosquamous, or adenocarcinoma of the cervix and must not have&#xD;
             received prior systemic therapy for recurrent or stage IVB cervical cancer (Arms D, E,&#xD;
             and H only).&#xD;
&#xD;
          -  Must have squamous, adenosquamous, or adenocarcinoma of the cervix and progressed on&#xD;
             or after at least one but no more than two prior systemic therapies for recurrent or&#xD;
             stage IVB cervical cancer (Arms F and G only).&#xD;
&#xD;
          -  Must have baseline measurable disease per RECIST v1.1.&#xD;
&#xD;
          -  Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (All&#xD;
             Arms).&#xD;
&#xD;
          -  Is not pregnant, breastfeeding, or expecting to conceive children within the projected&#xD;
             duration of the trial and for at least 6 months after the last trial treatment&#xD;
             administration&#xD;
&#xD;
          -  Participants of childbearing potential must agree to use adequate contraception during&#xD;
             and for 6 months after the last dose of trial treatment administration.&#xD;
&#xD;
          -  Must sign an informed consent form (ICF) indicating the trial subject understands the&#xD;
             purpose of and procedures required for the trial and are willing to participate in the&#xD;
             trial (All Arms).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has clinically relevant bilateral hydronephrosis which cannot be alleviated by&#xD;
             ureteral stents or percutaneous drainage. (All Arms)&#xD;
&#xD;
          -  Has clinical signs or symptoms of gastrointestinal obstruction and requires parenteral&#xD;
             hydration and/or nutrition. Post-operative obstructions within 4 weeks of abdominal&#xD;
             surgery are permitted. (All Arms)&#xD;
&#xD;
          -  Has clinically significant bleeding issues or risks&#xD;
&#xD;
               -  Prior history (within 3 months) or current evidence of hemoptysis (1/2 teaspoon&#xD;
                  or more) (Arm A and bevacizumab-eligible participants in Arm H)&#xD;
&#xD;
               -  Recent (within 4 weeks of first dose of trial treatment) clinically significant&#xD;
                  gastrointestinal or vaginal bleeding requiring PRBC transfusion (Arms A and H&#xD;
                  only)&#xD;
&#xD;
               -  Recent (within 4 weeks of first dose of trial treatment) evidence of wound&#xD;
                  healing complications that require medical intervention (Arms A and H only)&#xD;
&#xD;
          -  Has active ocular surface disease at baseline. Subjects with prior history of&#xD;
             cicatricial conjunctivitis are ineligible (All Arms).&#xD;
&#xD;
          -  Clinically significant cardiac disease&#xD;
&#xD;
          -  Requires anti-coagulation therapy (Arms A and H only)&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Arizona Oncology Associates</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Univ 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>Olive View - UCLA Research and Education Institute</name>
      <address>
        <city>Sylmar</city>
        <state>California</state>
        <zip>91342</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baptist MD Anderson Cancer Center</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Augusta University</name>
      <address>
        <city>Augusta</city>
        <state>Georgia</state>
        <zip>30912</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60525</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University School of Medicine</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Medical Center</name>
      <address>
        <city>Westwood</city>
        <state>Kansas</state>
        <zip>66205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oschner Clinic</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70121</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>Billings Clinic Cancer Center</name>
      <address>
        <city>Billings</city>
        <state>Montana</state>
        <zip>59101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montana Cancer Consortium</name>
      <address>
        <city>Billings</city>
        <state>Montana</state>
        <zip>59102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SUNY Downstate Medical Center</name>
      <address>
        <city>Brooklyn</city>
        <state>New York</state>
        <zip>11203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of North Carolina Chapel Hill</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27514</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati Physicians Group</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ohio State University Wexner Medical Center</name>
      <address>
        <city>Hilliard</city>
        <state>Ohio</state>
        <zip>43026</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fox Chase Cancer Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Magee-Womens Hospital of UPMC</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brown University - Women's and Infant Hospital</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Francis Hospital Cancer Center</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Huntsman Cancer Center</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carilion Clinic</name>
      <address>
        <city>Roanoke</city>
        <state>Virginia</state>
        <zip>24016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AZ Sint-Jan</name>
      <address>
        <city>Brugge</city>
        <zip>8000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cliniques universitaires Saint-Luc</name>
      <address>
        <city>Brussels</city>
        <zip>1200</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cliniques Universitaires Saint-Luc</name>
      <address>
        <city>Bruxelles</city>
        <zip>1200</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Grand Hôpital de Charleroi</name>
      <address>
        <city>Charleroi</city>
        <zip>6000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitair Ziekenhuis Antwerpen (UZA)</name>
      <address>
        <city>Edegem</city>
        <zip>2650</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitair Ziekenhuis Gent</name>
      <address>
        <city>Gent</city>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Leuven</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaire Ziekenhuizen Leuven,</name>
      <address>
        <city>Leuven</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier de l'Ardenne</name>
      <address>
        <city>Libramont</city>
        <zip>6800</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Universitaire (CHU) de Liège</name>
      <address>
        <city>Liège</city>
        <zip>4000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Grand Hôpital de Charleroi</name>
      <address>
        <city>Loverval</city>
        <zip>6280</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU UCL Namur</name>
      <address>
        <city>Namur</city>
        <zip>5000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sainte-Elisabeth</name>
      <address>
        <city>Namur</city>
        <zip>5000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fakultni nemocnice Olomouc</name>
      <address>
        <city>Olomouc</city>
        <zip>775 20</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fakultni nemocnice Olomouc</name>
      <address>
        <city>Olomouc</city>
        <zip>77520</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fakultni nemocnice Ostrava</name>
      <address>
        <city>Ostrava-Poruba</city>
        <zip>70852</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vseobecna fakultni nemocnice v Praze</name>
      <address>
        <city>Praha 2</city>
        <zip>128 51</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vseobecna fakultni nemocnice v Praze</name>
      <address>
        <city>Praha 2</city>
        <zip>12851</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fakultni nemocnice Bulovka</name>
      <address>
        <city>Praha</city>
        <zip>180 81</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nemocnice Na Bulovce</name>
      <address>
        <city>Praha</city>
        <zip>18081</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rigshospitalet</name>
      <address>
        <city>Copenhagen</city>
        <zip>5072</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cork University Hospital</name>
      <address>
        <city>Cork</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mater Misericordiae University Hospital</name>
      <address>
        <city>Dublin</city>
        <zip>D07 R2WY</zip>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Waterford Regional Hospital</name>
      <address>
        <city>Waterford</city>
        <zip>X91 ER8E</zip>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Waterford</name>
      <address>
        <city>Waterford</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Cannizzaro</name>
      <address>
        <city>Catania</city>
        <zip>95100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IEO Istituto Europeo di Oncologia</name>
      <address>
        <city>Milano</city>
        <zip>20141</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Nazionale Tumori Fondazione G. Pascale</name>
      <address>
        <city>Napoli</city>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione Policlinico Universitario Agostino Gemelli IRCCS</name>
      <address>
        <city>Roma</city>
        <zip>00168</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione Policlinico Universitario Agostino Gemelli IRCCS</name>
      <address>
        <city>Rome</city>
        <zip>00168</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Amsterdam UMC, Locatie AMC</name>
      <address>
        <city>Amsterdam</city>
        <zip>1105 AZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AMC Medical Research</name>
      <address>
        <city>Amsterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitair Medisch Centrum Groningen (UMCG)</name>
      <address>
        <city>Groningen</city>
        <zip>9713 GZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Radboudumc</name>
      <address>
        <city>Nijmegen</city>
        <zip>6525 GA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Erasmus Medisch Centrum</name>
      <address>
        <city>Rotterdam</city>
        <zip>3015 CC</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Erasmus University Medical Center Rotterdam</name>
      <address>
        <city>Rotterdam</city>
        <zip>3015</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UMC Utrecht</name>
      <address>
        <city>Utrecht</city>
        <zip>3508 GA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Medical Center Utrecht (UMC Utrecht)</name>
      <address>
        <city>Utrecht</city>
        <zip>3584</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <zip>8035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Reina Sofia</name>
      <address>
        <city>Cordoba</city>
        <zip>14004</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen de la Arrixaca</name>
      <address>
        <city>El Palmar</city>
        <zip>30120</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital 12 De Octubre</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baskent University Adana Application and Research Center</name>
      <address>
        <city>Adana</city>
        <zip>01220</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baskent University Ankara Hospital</name>
      <address>
        <city>Ankara</city>
        <zip>06490</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Velindre Cancer Centre</name>
      <address>
        <city>Cardiff</city>
        <state>South Glamorgan</state>
        <zip>CF14 2TL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beatson West of Scotland Cancer Centre</name>
      <address>
        <city>Glasgow</city>
        <state>Strathclyde</state>
        <zip>G12 OYN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Marsden Hospital- Sutton</name>
      <address>
        <city>Sutton</city>
        <state>Surrey</state>
        <zip>SM2 5PT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Czechia</country>
    <country>Denmark</country>
    <country>Ireland</country>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>Spain</country>
    <country>Turkey</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>December 13, 2018</study_first_submitted>
  <study_first_submitted_qc>December 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 24, 2018</study_first_posted>
  <last_update_submitted>January 9, 2023</last_update_submitted>
  <last_update_submitted_qc>January 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 11, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>cervical carcinoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Uterine Cervical Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bevacizumab</mesh_term>
    <mesh_term>Pembrolizumab</mesh_term>
    <mesh_term>Tisotumab vedotin</mesh_term>
    <mesh_term>Carboplatin</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/NCT03786081
org study id: GCT1015-05
secondary id: InnovaTV 205
secondary id: MK3475 KN 834
secondary id: ENGOT-cx8
secondary id: GOG-3024
nct id: NCT03786081
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is an open label, multi-center trial of tisotumab vedotin monotherapy and in combination
      with bevacizumab, pembrolizumab, or carboplatin in subjects with recurrent or stage IVB
      cervical cancer.

      The trial consists of two-parts a dose escalation part and an expansion part. The expansion
      part of the trial will be initiated once the Recommended Phase 2 Dose (RP2D) of the
      combinations have been determined in the dose escalation part.
The dose escalation part will occur in participants with cervical cancer who have progressed
      during or after standard of care therapy and who are intolerant or ineligible to receive
      standard of care treatments. Arm A will be conducted by escalating doses of both tisotumab
      vedotin and bevacizumab. Dose escalations of the tisotumab vedotin + pembrolizumab and
      tisotumab vedotin + carboplatin combinations (Arms B and C, respectively) will be conducted
      by combining fixed doses of either pembrolizumab or carboplatin with increasing doses of
      tisotumab vedotin.

      The dose expansion part of this study (Arms D through H) will be conducted in 2 populations:
      participants with cervical cancer who have not received prior systemic therapy for recurrent
      or stage IVB cervical cancer (Arms D, E, and H) and participants with cervical cancer who
      have progressed on or after at least 1 but no more than 2 prior systemic therapies (Arms F
      and G).

      Participants enrolled to Arms D, E, F and H will receive the RP2D of tisotumab vedotin
      established in the dose escalation part. Participants enrolled to Arm G will receive
      tisotumab vedotin weekly (at a dose lower than subjects in all other Arms) for three weeks
      and 1 week off (28-day treatment cycle).
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Dose escalation: Dose Limiting Toxicities (DLTs)
time frame: DLTs will be identified during the first treatment cycle (21 day cycles)
description: To establish the MTD and RP2D of tisotumab vedotin in combination
measure: Dose expansion: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
time frame: approximately 2 years
description: Objective response is defined as confirmed partial response (PR) or complete response (CR)
measure: Number of adverse events (AEs)
time frame: up to 2 years
description: Any untoward medical occurrence in a clinical trial participant whether or not considered related to the medicinal product.
measure: Dose escalation: ORR per RECIST v1.1
time frame: approximately 2 years
description: Objective response is defined as confirmed PR or CR.
measure: Duration of Response (DOR) per RECIST v1.1 by investigator assessment
time frame: approximately 2 years
description: Will be calculated from the date of initial documentation of a response (CR or PR) to the date of first documented evidence of progressive disease (PD) or death.
measure: Time to Response (TTR) per RECIST v1.1 by investigator assessment
time frame: approximately 2 years
description: Will be calculated from the date of the first dose to the date of the initial documentation of response (CR or PR).
measure: Progression free survival (PFS) per RECIST v1.1 by investigator assessment
time frame: approximately 2 years
description: The time from the date of the first trial drug administration to the date of the first documented disease progression or death due to any cause.
measure: Overall Survival (OS)
time frame: approximately 2 years
description: The time from the date of the first trial drug administration to the date of death due to any cause.
measure: Maximum concentration (Cmax) (All Arms except G)
time frame: Up to 42 days
description: Pharmacokinetic (PK) parameter
measure: Cmax (Arm G only)
time frame: Up to 2 years
description: PK parameter
measure: Trough Concentration (Ctrough) (All Arms)
time frame: Up to 2 years
description: PK parameter
measure: Area under the concentration-time curve (AUC) (All Arms except G)
time frame: Through 21 days after first dose
description: PK parameter
measure: AUC (Arm G only)
time frame: Through 8 days after first dose
description: PK parameter
measure: Anti-drug antibodies (ADAs)
time frame: Up to 2 years
arm group label: A: Tisotumab Vedotin + bevacizumab
arm group type: Experimental
description: Dose escalation: Tisotumab vedotin in combination with bevacizumab once every three weeks in previously treated patients
arm group label: B: Tisotumab vedotin + pembrolizumab
arm group type: Experimental
description: Dose escalation: Tisotumab vedotin in combination with pembrolizumab once every three weeks in previously treated patients
arm group label: C: Tisotumab vedotin + carboplatin
arm group type: Experimental
description: Dose escalation: Tisotumab vedotin in combination with carboplatin once every three weeks in previously treated patients
arm group label: D: Tisotumab vedotin + carboplatin
arm group type: Experimental
description: Dose expansion:Tisotumab vedotin in combination with carboplatin once every three weeks in previously untreated patients
arm group label: E: Tisotumab vedotin + pembrolizumab
arm group type: Experimental
description: Dose expansion: Tisotumab vedotin in combination with pembrolizumab once every three weeks in previously untreated patients
arm group label: F: Tisotumab vedotin + pembrolizumab
arm group type: Experimental
description: Dose expansion: Tisotumab vedotin in combination with pembrolizumab once every three weeks in previously treated patients
arm group label: G: Tisotumab vedotin monotherapy
arm group type: Experimental
description: Dose expansion: Tisotumab vedotin monotherapy weekly for three weeks and 1 week off (28 day treatment cycle) in previously treated patients.
arm group label: H: Tisotumab vedotin + pembrolizumab + carboplatin +/- bevacizumab
arm group type: Experimental
description: Dose expansion: Tisotumab vedotin in combination with pembrolizumab and carboplatin with or without bevacizumab once every three weeks in previously untreated patients
intervention type: Drug
intervention name: Tisotumab Vedotin
description: Given into the vein (IV)
arm group label: A: Tisotumab Vedotin + bevacizumab
arm group label: B: Tisotumab vedotin + pembrolizumab
arm group label: C: Tisotumab vedotin + carboplatin
arm group label: D: Tisotumab vedotin + carboplatin
arm group label: E: Tisotumab vedotin + pembrolizumab
arm group label: F: Tisotumab vedotin + pembrolizumab
arm group label: G: Tisotumab vedotin monotherapy
arm group label: H: Tisotumab vedotin + pembrolizumab + carboplatin +/- bevacizumab
other name: TIVDAK
intervention type: Drug
intervention name: Bevacizumab
description: Given via IV
arm group label: A: Tisotumab Vedotin + bevacizumab
arm group label: H: Tisotumab vedotin + pembrolizumab + carboplatin +/- bevacizumab
other name: Avastin
intervention type: Drug
intervention name: Pembrolizumab
description: Given via IV
arm group label: B: Tisotumab vedotin + pembrolizumab
arm group label: E: Tisotumab vedotin + pembrolizumab
arm group label: F: Tisotumab vedotin + pembrolizumab
arm group label: H: Tisotumab vedotin + pembrolizumab + carboplatin +/- bevacizumab
other name: Keytruda
intervention type: Drug
intervention name: Carboplatin
description: Given via IV
arm group label: C: Tisotumab vedotin + carboplatin
arm group label: D: Tisotumab vedotin + carboplatin
arm group label: H: Tisotumab vedotin + pembrolizumab + carboplatin +/- bevacizumab
other name: Paraplatin
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
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country: Belgium
country: Czechia
country: Denmark
country: Ireland
country: Italy
country: Netherlands
country: Spain
country: Turkey
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Uterine Cervical Neoplasms
mesh term: Bevacizumab
mesh term: Pembrolizumab
mesh term: Tisotumab vedotin
mesh term: Carboplatin