<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/NCT03788746</url>
  </required_header>
  <id_info>
    <org_study_id>D419BR00008</org_study_id>
    <nct_id>NCT03788746</nct_id>
  </id_info>
  <brief_title>Prevalence of PD-L1 Expression in Patients With Advanced Urothelial Carcinoma</brief_title>
  <acronym>PREVAIL</acronym>
  <official_title>A Prospective, Non-Interventional Study to Assess the Prevalence of PD-L1 Expression in the First-Line Setting of Locally Advanced/Unresectable or Metastatic Urothelial Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AstraZeneca</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to assess the prevalence of pre-treatment tumor tissue PD-L1&#xD;
      expression in patients diagnosed with advanced urothelial carcinoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Advanced urothelial carcinoma (UC) (locally advanced/unresectable or metastatic UC) is a&#xD;
      fatal disease with 5-year survival rate of 5%. The most frequently studied diagnostic for&#xD;
      advanced UC is the programmed death-ligand 1 (PD-L1) protein expression in tumor tissue. A&#xD;
      better understanding of PD-L1 expression in a &quot;real world&quot; setting could help understand its&#xD;
      clinical utility in the management and decision making in advanced UC and clinical trial&#xD;
      design&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 17, 2019</start_date>
  <completion_date type="Actual">May 25, 2023</completion_date>
  <primary_completion_date type="Actual">January 12, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Categorization of PD-L1 results (dichotomous, high vs. low) based on pre-treatment tissue samples.</measure>
    <time_frame>24 months</time_frame>
    <description>The proportion of advanced UC patients with biomarker PD-L1 high results will be calculated.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To assess the association of pre-treatment tumor tissue PD-L1 expression with pre-treatment tumor tissue TMB (tTMB) based on the chosen assay</measure>
    <time_frame>24 months</time_frame>
    <description>Assay results for pre-treatment tTMB will be assessed by pre-treatment tumor tissue PD-L1 expression status.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To describe the objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) as well as treatment patterns in the 1L setting of advanced UC</measure>
    <time_frame>54 months</time_frame>
    <description>1L advanced UC treatment patterns (such as regimen/agents used, start (first dose) and stop (last dose) dates, reasons for cis/carboplatin ineligibility) will be collected.&#xD;
Objective Response: complete or partial response based on healthcare provider (HCP) assessment; Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria highly recommended Progression: evidence malignancy has become worse or spreads in the body (based on HCP assessment).&#xD;
Objective response and survival endpoints (overall, stratified by PD-L1 expression [high vs. low] including the following: ORR: The proportion of patients with a complete or partial response based on HCP assessment; PFS: The time from the start of 1L advanced UC treatment until progression or death (any cause); and OS: The time from start of 1L advanced UC treatment until death (any cause)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To assess the association between pre-treatment tumor tissue PD-L1 expression with objective response, PFS, and OS among treated patients (anti PD-L1/PD-1, chemotherapy, other)</measure>
    <time_frame>60 months</time_frame>
    <description>Objective response, PFS, and OS (defined above) will be stratified by pre-treatment tumor tissue PD-L1 expression, and among patients treated with anti-PD-L1/PD-1 or chemotherapy or other.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>To assess the association of pre-treatment tumor tissue PD-L1 with pre-treatment bTMB</measure>
    <time_frame>24 months</time_frame>
    <description>bTMB levels will be summarized among the subset of patients with blood available for testing using the chosen assay who are newly diagnosed with advanced UC and have yet to start 1L treatment. Results for TMB can range from 0 (non-shedder) to very high values &gt;50 mut/Mb (no maximum has been determined). The results for pre-treatment bTMB will be presented by PD-L1 results (high vs low).</description>
  </other_outcome>
  <other_outcome>
    <measure>To assess changes in ctDNA levels (variant allele fractions [VAFs]) at 3 points of sample testing: (1) Before starting 1L treatment (pre-treatment) (2) before initiating treatment on day 1 of cycle 3, and (3) at the time of progression (if applicable)</measure>
    <time_frame>60 months</time_frame>
    <description>ctDNA levels will be summarized among the subset of patients with blood available for testing using the chosen assay who are newly diagnosed with advanced UC and have yet to start 1L treatment. VAF is the relative frequency of alleles at a particular locus in a population, expressed as a percentage, ranging from 0.3% to 100%. Changes in ctDNA levels at 3 points of sample testing will be assessed.</description>
  </other_outcome>
  <other_outcome>
    <measure>To examine the correlation between pre-treatment tTMB and bTMB values</measure>
    <time_frame>24 months</time_frame>
    <description>bTMB levels will be summarized among the subset of patients with blood available for testing using the chosen assay who are newly diagnosed with advanced UC and have yet to start 1L treatment. Assay results for pre-treatment tTMB will be assessed by pre-treatment bTMB results.</description>
  </other_outcome>
  <other_outcome>
    <measure>To assess the prognostic value of pre-treatment and changes to ctDNA levels, and pre-treatment tTMB compared to bTMB, for outcomes of ORR, PFS, and OS</measure>
    <time_frame>60 months</time_frame>
    <description>bTMB and ctDNA levels will be summarized among the subset of patients with blood available for testing using the chosen assay who are newly diagnosed with advanced UC and have yet to start 1L treatment. Objective response, PFS, and OS (defined in secondary outcome measures) will be assessed by the following: changes to ctDNA levels (VAFs) at 3 timepoints (defined above); and pre-treatment tTMB assay results compared with pre-treatment bTMB assay results.</description>
  </other_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">178</enrollment>
  <condition>Urothelial Carcinoma</condition>
  <arm_group>
    <arm_group_label>Patients diagnosed with advanced urothelial carcinoma</arm_group_label>
    <description>Patients with a confirmed diagnosis of advanced urothelial carcinoma, prior to or during first line therapy, who have available tumor tissue samples collected as part of standard of care</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Tissue, Plasma&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patient population with care managed in a community setting in the United States&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Provision of written informed consent&#xD;
&#xD;
          -  Age ≥18 years old&#xD;
&#xD;
          -  Patient must have advanced UC confirmed by their HCP; histologically- confirmed&#xD;
             diagnosis of UC an dHCP-confirmed advanced UC.&#xD;
&#xD;
          -  Patient must be either currently receiving 1L systemic treatment for their advanced UC&#xD;
             or will be starting 1L systemic treatment (i.e. &quot;newly diagnosed&quot; advanced UC; 1L&#xD;
             therapy is defined as the first systemic therapy given for advanced UC).&#xD;
&#xD;
          -  Patient remains eligible for the study if they received neoadjuvant or adjuvant&#xD;
             platinum-based chemotherapy if their recurrence was more than 12 months after their&#xD;
             last chemotherapy dose.&#xD;
&#xD;
          -  Radio-sensitizing chemotherapy as part of chemoradiation is NOT counted as neoadjuvant&#xD;
             or adjuvant chemotherapy; thus, the 12-month interval mention above does not apply,&#xD;
             and the patient would be eligible&#xD;
&#xD;
          -  Patients with available tumor tissue sample (fresh or archival - up to 3 years old)&#xD;
             that was collected as part of SoC any time prior to 1L treatment for advanced UC with&#xD;
             a target of 18 slides (7 minimum) available for biomarker testing (PD-L1 and tTMB).&#xD;
             Already prepared slides must have been cut within 6 months prior to PD-L1 testing.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients concurrently enrolled in other clinical trials that prohibit their&#xD;
             participation in a non-interventional study&#xD;
&#xD;
          -  Patient has resectable localized UC and has refused surgery&#xD;
&#xD;
          -  Patients with history of non-urothelial active malignancy that completed therapy&#xD;
             within 2 years from study enrollment except:&#xD;
&#xD;
               -  Any resected in situ carcinoma or non-melanoma skin cancer&#xD;
&#xD;
               -  Localized (early stage) cancer treated with curative intent (without evidence of&#xD;
                  recurrence and intent for further therapy) and in which no systemic therapy was&#xD;
                  indicated&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>130 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Petros Grivas, MD</last_name>
    <role>Study Chair</role>
    <affiliation>University of Washington</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Joshua Meeks</last_name>
    <role>Study Chair</role>
    <affiliation>Northwestern University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Glendale</city>
        <state>California</state>
        <zip>91204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90048</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90067</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Monterey</city>
        <state>California</state>
        <zip>93940</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Santa Rosa</city>
        <state>California</state>
        <zip>95403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Englewood</city>
        <state>Colorado</state>
        <zip>80113</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hartford</city>
        <state>Connecticut</state>
        <zip>06106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Stamford</city>
        <state>Connecticut</state>
        <zip>06904</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Boca Raton</city>
        <state>Florida</state>
        <zip>33486</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hialeah</city>
        <state>Florida</state>
        <zip>33016-1815</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32256</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Augusta</city>
        <state>Georgia</state>
        <zip>30912</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Roswell</city>
        <state>Georgia</state>
        <zip>30076</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Geneva</city>
        <state>Illinois</state>
        <zip>60134</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Harvey</city>
        <state>Illinois</state>
        <zip>60426</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Lake Barrington</city>
        <state>Illinois</state>
        <zip>60010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Naperville</city>
        <state>Illinois</state>
        <zip>60540</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Greenwood</city>
        <state>Indiana</state>
        <zip>46143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Lafayette</city>
        <state>Indiana</state>
        <zip>47904</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Muncie</city>
        <state>Indiana</state>
        <zip>47303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Cedar Rapids</city>
        <state>Iowa</state>
        <zip>52403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Waterloo</city>
        <state>Iowa</state>
        <zip>50703</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Wichita</city>
        <state>Kansas</state>
        <zip>67226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Baton Rouge</city>
        <state>Louisiana</state>
        <zip>70809</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Shreveport</city>
        <state>Louisiana</state>
        <zip>71106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Brewer</city>
        <state>Maine</state>
        <zip>04412</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Lewiston</city>
        <state>Maine</state>
        <zip>04240</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49503-2563</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Duluth</city>
        <state>Minnesota</state>
        <zip>55805</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Saint Cloud</city>
        <state>Minnesota</state>
        <zip>56303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bridgeton</city>
        <state>Missouri</state>
        <zip>63044</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Berkeley Heights</city>
        <state>New Jersey</state>
        <zip>07922</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>East Brunswick</city>
        <state>New Jersey</state>
        <zip>08816</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Englewood</city>
        <state>New Jersey</state>
        <zip>07631</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Freehold</city>
        <state>New Jersey</state>
        <zip>07728</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Little Silver</city>
        <state>New Jersey</state>
        <zip>07739</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Mount Laurel</city>
        <state>New Jersey</state>
        <zip>08054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Albany</city>
        <state>New York</state>
        <zip>12206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Johnson City</city>
        <state>New York</state>
        <zip>13790</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Port Jefferson Station</city>
        <state>New York</state>
        <zip>11776</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Greenville</city>
        <state>North Carolina</state>
        <zip>27834</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45267</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kettering</city>
        <state>Ohio</state>
        <zip>45429</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Myrtle Beach</city>
        <state>South Carolina</state>
        <zip>29572</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Knoxville</city>
        <state>Tennessee</state>
        <zip>37920</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Temple</city>
        <state>Texas</state>
        <zip>76508</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>The Woodlands</city>
        <state>Texas</state>
        <zip>77380</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Virginia Beach</city>
        <state>Virginia</state>
        <zip>23462</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Olympia</city>
        <state>Washington</state>
        <zip>98502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Renton</city>
        <state>Washington</state>
        <zip>98055</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tacoma</city>
        <state>Washington</state>
        <zip>98405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Wenatchee</city>
        <state>Washington</state>
        <zip>98801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>November 27, 2018</study_first_submitted>
  <study_first_submitted_qc>December 23, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 28, 2018</study_first_posted>
  <last_update_submitted>June 29, 2023</last_update_submitted>
  <last_update_submitted_qc>June 29, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Urothelial Carcinoma</keyword>
  <keyword>Registry</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Transitional Cell</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.&#xD;
Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared</ipd_description>
    <ipd_time_frame>AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.</ipd_time_frame>
    <ipd_access_criteria>When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.</ipd_access_criteria>
    <ipd_url>https://astrazenecagroup-dt.pharmacm.com/DT/Home</ipd_url>
  </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/NCT03788746
org study id: D419BR00008
nct id: NCT03788746
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to assess the prevalence of pre-treatment tumor tissue PD-L1
      expression in patients diagnosed with advanced urothelial carcinoma.
Advanced urothelial carcinoma (UC) (locally advanced/unresectable or metastatic UC) is a
      fatal disease with 5-year survival rate of 5%. The most frequently studied diagnostic for
      advanced UC is the programmed death-ligand 1 (PD-L1) protein expression in tumor tissue. A
      better understanding of PD-L1 expression in a "real world" setting could help understand its
      clinical utility in the management and decision making in advanced UC and clinical trial
      design
observational model: Cohort
time perspective: Prospective
measure: Categorization of PD-L1 results (dichotomous, high vs. low) based on pre-treatment tissue samples.
time frame: 24 months
description: The proportion of advanced UC patients with biomarker PD-L1 high results will be calculated.
measure: To assess the association of pre-treatment tumor tissue PD-L1 expression with pre-treatment tumor tissue TMB (tTMB) based on the chosen assay
time frame: 24 months
description: Assay results for pre-treatment tTMB will be assessed by pre-treatment tumor tissue PD-L1 expression status.
measure: To describe the objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) as well as treatment patterns in the 1L setting of advanced UC
time frame: 54 months
description: 1L advanced UC treatment patterns (such as regimen/agents used, start (first dose) and stop (last dose) dates, reasons for cis/carboplatin ineligibility) will be collected.
Objective Response: complete or partial response based on healthcare provider (HCP) assessment; Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria highly recommended Progression: evidence malignancy has become worse or spreads in the body (based on HCP assessment).
Objective response and survival endpoints (overall, stratified by PD-L1 expression [high vs. low] including the following: ORR: The proportion of patients with a complete or partial response based on HCP assessment; PFS: The time from the start of 1L advanced UC treatment until progression or death (any cause); and OS: The time from start of 1L advanced UC treatment until death (any cause)
measure: To assess the association between pre-treatment tumor tissue PD-L1 expression with objective response, PFS, and OS among treated patients (anti PD-L1/PD-1, chemotherapy, other)
time frame: 60 months
description: Objective response, PFS, and OS (defined above) will be stratified by pre-treatment tumor tissue PD-L1 expression, and among patients treated with anti-PD-L1/PD-1 or chemotherapy or other.
measure: To assess the association of pre-treatment tumor tissue PD-L1 with pre-treatment bTMB
time frame: 24 months
description: bTMB levels will be summarized among the subset of patients with blood available for testing using the chosen assay who are newly diagnosed with advanced UC and have yet to start 1L treatment. Results for TMB can range from 0 (non-shedder) to very high values >50 mut/Mb (no maximum has been determined). The results for pre-treatment bTMB will be presented by PD-L1 results (high vs low).
measure: To assess changes in ctDNA levels (variant allele fractions [VAFs]) at 3 points of sample testing: (1) Before starting 1L treatment (pre-treatment) (2) before initiating treatment on day 1 of cycle 3, and (3) at the time of progression (if applicable)
time frame: 60 months
description: ctDNA levels will be summarized among the subset of patients with blood available for testing using the chosen assay who are newly diagnosed with advanced UC and have yet to start 1L treatment. VAF is the relative frequency of alleles at a particular locus in a population, expressed as a percentage, ranging from 0.3% to 100%. Changes in ctDNA levels at 3 points of sample testing will be assessed.
measure: To examine the correlation between pre-treatment tTMB and bTMB values
time frame: 24 months
description: bTMB levels will be summarized among the subset of patients with blood available for testing using the chosen assay who are newly diagnosed with advanced UC and have yet to start 1L treatment. Assay results for pre-treatment tTMB will be assessed by pre-treatment bTMB results.
measure: To assess the prognostic value of pre-treatment and changes to ctDNA levels, and pre-treatment tTMB compared to bTMB, for outcomes of ORR, PFS, and OS
time frame: 60 months
description: bTMB and ctDNA levels will be summarized among the subset of patients with blood available for testing using the chosen assay who are newly diagnosed with advanced UC and have yet to start 1L treatment. Objective response, PFS, and OS (defined in secondary outcome measures) will be assessed by the following: changes to ctDNA levels (VAFs) at 3 timepoints (defined above); and pre-treatment tTMB assay results compared with pre-treatment bTMB assay results.
arm group label: Patients diagnosed with advanced urothelial carcinoma
description: Patients with a confirmed diagnosis of advanced urothelial carcinoma, prior to or during first line therapy, who have available tumor tissue samples collected as part of standard of care
Tissue, Plasma
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 130 Years
healthy volunteers: No
last name: Petros Grivas, MD
role: Study Chair
affiliation: University of Washington
last name: Joshua Meeks
role: Study Chair
affiliation: Northwestern University
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Transitional Cell
sharing ipd: Yes
ipd description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared
ipd time frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
ipd access criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
ipd url: https://astrazenecagroup-dt.pharmacm.com/DT/Home