<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/NCT03007719</url>
  </required_header>
  <id_info>
    <org_study_id>16709</org_study_id>
    <secondary_id>NCI-2017-01323</secondary_id>
    <nct_id>NCT03007719</nct_id>
  </id_info>
  <brief_title>Functional Imaging of T-Cell Activation With [18F]F-AraG in Urothelial Carcinoma Patients Receiving Neoadjuvant Therapy or Patients With Cancer Receiving Standard of Care Anti-PD-1/L1</brief_title>
  <official_title>Functional Imaging of T-Cell Activation With [18F]F-AraG in Urothelial Carcinoma Patients Receiving Neoadjuvant Therapy or Patients With Cancer Receiving Standard of Care Anti-PD-1/L1</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Lawrence Fong</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>CellSight Technologies, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, San Francisco</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 phase II trial studies how well fluorine F 18 Ara-G positron emission tomography&#xD;
      (PET)/magnetic resonance (MR) imaging works in measuring clinical response to atezolizumab or&#xD;
      patients with cancer receiving standard of care Anti-PD-1/L1. Diagnostic procedures, such as&#xD;
      fluorine F 18 Ara-G PET/MR imaging, may help measure a patient's response to standard of care&#xD;
      atezolizumab or Anti-PD-1/L1 treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To assess the change in fluorine F 18 Ara-G ([18F]F-AraG) uptake in primary and/or&#xD;
      metastatic tumor(s) on whole-body [18F]F-AraG PET/MR imaging associated with neoadjuvant&#xD;
      atezolizumab and standard of care (SOC) anti-PD-1 or anti-PD-L1 treatment.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To correlate change in [18F]F-AraG uptake within the primary tumor with clinical and&#xD;
      pathologic response in patients treated with neoadjuvant atezolizumab. (Cohort 1) II. To&#xD;
      assess [18F]F-AraG uptake in lymphoid organs before and after anti-PD-1 or anti-PD-L1&#xD;
      treatment. (Cohort 1 and 2)&#xD;
&#xD;
      OUTLINE: Patients are assigned to 1 or 2 cohorts.&#xD;
&#xD;
      COHORT I (NEOADJUVANT COHORT): Patients receive fluorine F 18 Ara-G intravenously (IV) and&#xD;
      undergo PET/MR imaging over 1.5-3 hours within 7 days of starting standard of care&#xD;
      atezolizumab and within 7 days before surgery.&#xD;
&#xD;
      COHORT II (SOC COHORT): Patients receive fluorine F 18 Ara-G IV and undergo PET/MR imaging&#xD;
      over 1.5-3 hours within 7 days of initiating course 1 of anti-PD-1 or anti-PD-L1 therapy and&#xD;
      between day 15 of course 1 and day 7 of course 2 of anti-PD-1 or anti-PD-L1 treatment.&#xD;
&#xD;
      After completion of study, patients are followed up at days 2 and 8.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Low Accrual&#xD;
  </why_stopped>
  <start_date type="Actual">March 7, 2017</start_date>
  <completion_date type="Actual">January 11, 2019</completion_date>
  <primary_completion_date type="Actual">January 11, 2019</primary_completion_date>
  <phase>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>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change Between Pre-treatment and Post-treatment SUVmax (Standardized Uptake Values) in the Primary and/or Metastatic Tumor(s) on Whole-body [18F]F-AraG Positron Emission Tomography/Magnetic Resonance (PET/MR) Imaging by Study Cohort.</measure>
    <time_frame>Up to 2 weeks</time_frame>
    <description>The nonparametric paired Wilcoxon Signed-rank test will be used to assess differences in SUVmax before and after treatment. The log2 ratio of post-treatment versus baseline SUVmax within the tumor and lymphoid tissues will also be calculated</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Compare Change in SUVmax of the Primary Tumor in Patients Who Achieve Pathologic Downstaging or Clinical Response and Those Without Pathologic or Clinical Response at Time of Surgery in Patients Receiving Neoadjuvant Atezolizumab (Cohort 1)</measure>
    <time_frame>Up to 6 weeks</time_frame>
    <description>To correlate change in SUVmax to clinical and/or pathologic response, patients will be divided into two groups: those who achieved clinical response and/or pathologic downs-staging, and those who did not. The median and interquartile range of change in SUVmax from baseline to pre-surgery in the different groups will be descriptively reported. For Cohort 1, clinical response will be determined by abdominal imaging performed &lt;30 days after the last dose of atezolizumab prior to cystectomy compared to baseline pre-treatment imaging using RECIST v1.1 criteria, as specified in the companion treatment protocol. For Cohort 1, pathologic response will be determined by evidence of down-staging (e.g. from muscle invasive to non-muscle invasive, or complete pathologic response) at the time of cystectomy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change Between Pre-treatment and Post-treatment SUVmax in Lymphoid Organs on Whole-body [18F]F-AraG PET/MR Imaging (Cohort 1 and 2)</measure>
    <time_frame>Up to 8 days</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">4</enrollment>
  <condition>Bladder Cancer</condition>
  <arm_group>
    <arm_group_label>Cohort 1: Neoadjuvant</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with localized bladder cancer who are eligible for the UCSF phase 2 clinical trial of neoadjuvant atezolizumab before definitive surgery (NCT02451423) (Cohort 1). For the neoadjuvant cohort, study participants will undergo whole body PET/MR imaging with [18F]F-AraG within 7 days of initiating atezolizumab and within 7 days before surgery. Approximately 12 patients will be enrolled.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2: Standard of Care (SOC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with any cancer type who are planned to initiate standard of care (SOC) anti-PD-1 or anti-PD-L1 treatment (Cohort 2). For the SOC cohort, study participants will undergo whole body PET/MR imaging with [18F]F-AraG within 7 days of initiating Cycle 1 anti-PD-1 or anti-PD-L1, and between Cycle 1 Day 15 (C1D15) and Cycle 2 Day 7 (C2D7) anti-PD-1 or anti-PD-L1. Approximately 19 patients will be enrolled.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fluorine F 18 Ara-G</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Cohort 1: Neoadjuvant</arm_group_label>
    <arm_group_label>Cohort 2: Standard of Care (SOC)</arm_group_label>
    <other_name>2'-deoxy-2'-fluoro-9-β-D-arabinofuranosylguanine</other_name>
    <other_name>VisAcT</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Positron Emission Tomography</intervention_name>
    <description>Undergo PET/MR imaging</description>
    <arm_group_label>Cohort 1: Neoadjuvant</arm_group_label>
    <arm_group_label>Cohort 2: Standard of Care (SOC)</arm_group_label>
    <other_name>PET</other_name>
    <other_name>PET Scan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Magnetic Resonance Imaging</intervention_name>
    <description>Undergo PET/MR imaging</description>
    <arm_group_label>Cohort 1: Neoadjuvant</arm_group_label>
    <arm_group_label>Cohort 2: Standard of Care (SOC)</arm_group_label>
    <other_name>MRI</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically or cytologically documented cancer to which anti-PD1 or anti-PDL1 are&#xD;
             approved therapies&#xD;
&#xD;
          -  Eligible for with plan to undergo neoadjuvant treatment with atezolizumab followed by&#xD;
             surgery as part of a companion study (NCT02451423), or planned to undergo treatment&#xD;
             with anti-PD-1 or anti-PD-L1 per standard of care&#xD;
&#xD;
          -  Must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST)&#xD;
             version (v)1.1 regardless of disease stage (e.g. localized, locally advanced, or&#xD;
             metastatic)&#xD;
&#xD;
          -  In female patients, negative pregnancy test with no plans to become pregnant during&#xD;
             the duration of the study&#xD;
&#xD;
          -  Able to provide informed consent and follow the study guidelines&#xD;
&#xD;
          -  Archival tumor tissue from biopsy or resection will be required for all patients;&#xD;
             archival tissue should be of good quality based on total and viable tumor contents;&#xD;
             fine needle aspiration, brushing, and cytologic cell pellets are not acceptable&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of prior treatment with immune checkpoint antibodies (e.g. anti-PD1,&#xD;
             anti-PDL1, anti-CTLA4 antibody) or co-stimulatory agonist antibodies (e.g. anti-41BB,&#xD;
             anti-OX40)&#xD;
&#xD;
             * Prior intravesical treatment with Bacillus Calmette-Guerin (BCG) is allowed;&#xD;
             however, the last dose must be at least 6 weeks from time of enrollment and patients&#xD;
             must have documented progressive disease at least 6 weeks from completion of last BCG&#xD;
&#xD;
          -  Diagnosis of immunodeficiency including history of human immunodeficiency virus (HIV)&#xD;
&#xD;
          -  Receiving systemic steroid therapy or any form of immunosuppressive therapy within 7&#xD;
             days prior to first injection of [18F]F-AraG&#xD;
&#xD;
             * Topical and inhaled corticosteroids are allowed&#xD;
&#xD;
          -  Prior allogeneic stem cell or solid organ transplant&#xD;
&#xD;
          -  Known psychiatric or substance abuse disorders that would interfere with cooperation&#xD;
             with the requirements of the study&#xD;
&#xD;
          -  Biopsy or resection of the primary tumor within 14 days the first injection of&#xD;
             [18F]F-AraG&#xD;
&#xD;
          -  Contraindication to magnetic resonance (MRI) imaging, as determined through review of&#xD;
             the University of California, San Francisco (UCSF) MRI screening form by study&#xD;
             investigator&#xD;
&#xD;
          -  Evidence of active infection within 14 days of study enrollment&#xD;
&#xD;
          -  Female patients who are pregnant or breastfeeding&#xD;
&#xD;
          -  Inability to receive furosemide (Lasix) in the opinion of the treating investigator&#xD;
&#xD;
          -  Patients that plan to receive off-label use of anti-PD1 or anti-PDL1&#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>Lawrence Fong, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Francisco</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California, San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94158</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>December 28, 2016</study_first_submitted>
  <study_first_submitted_qc>December 29, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 2, 2017</study_first_posted>
  <results_first_submitted>November 14, 2019</results_first_submitted>
  <results_first_submitted_qc>January 10, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">January 21, 2020</results_first_posted>
  <last_update_submitted>January 10, 2020</last_update_submitted>
  <last_update_submitted_qc>January 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 21, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of California, San Francisco</investigator_affiliation>
    <investigator_full_name>Lawrence Fong</investigator_full_name>
    <investigator_title>Professor in Residence</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Transitional Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fluorides</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>November 13, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/19/NCT03007719/ICF_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 20, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/19/NCT03007719/Prot_SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This study was closed due to low accrual. Only 4 patients were enrolled to this protocol and all were assigned to cohort 2</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Cohort 1: Neoadjuvant</title>
          <description>Patients with localized bladder cancer who are eligible for the University of California, San Francisco (UCSF) phase 2 clinical trial of neoadjuvant atezolizumab before definitive surgery (NCT02451423) (Cohort 1).</description>
        </group>
        <group group_id="P2">
          <title>Cohort 2: Standard of Care (SOC)</title>
          <description>Patients with any cancer type who are planned to initiate standard of care (SOC) anti-PD-1 or anti-PD-L1 treatment (Cohort 2).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Only four participants were consented and enrolled to this protocol</population>
      <group_list>
        <group group_id="B1">
          <title>Cohort 1: Neoadjuvant</title>
          <description>Patients with localized bladder cancer who are eligible for the University of California, San Francisco (UCSF) phase 2 clinical trial of neoadjuvant atezolizumab before definitive surgery (NCT02451423) (Cohort 1).</description>
        </group>
        <group group_id="B2">
          <title>Cohort 2: Standard of Care (SOC)</title>
          <description>Patients with any cancer type who are planned to initiate standard of care (SOC) anti-PD-1 or anti-PD-L1 treatment (Cohort 2).</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="0"/>
            <count group_id="B2" value="4"/>
            <count group_id="B3" value="4"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>60-69</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>70-79</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>80-89</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change Between Pre-treatment and Post-treatment SUVmax (Standardized Uptake Values) in the Primary and/or Metastatic Tumor(s) on Whole-body [18F]F-AraG Positron Emission Tomography/Magnetic Resonance (PET/MR) Imaging by Study Cohort.</title>
        <description>The nonparametric paired Wilcoxon Signed-rank test will be used to assess differences in SUVmax before and after treatment. The log2 ratio of post-treatment versus baseline SUVmax within the tumor and lymphoid tissues will also be calculated</description>
        <time_frame>Up to 2 weeks</time_frame>
        <population>SUVmax data not collected</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Neoadjuvant</title>
            <description>Patients with localized bladder cancer who are eligible for the University of California, San Francisco (UCSF) phase 2 clinical trial of neoadjuvant atezolizumab before definitive surgery (NCT02451423) (Cohort 1).</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Standard of Care (SOC)</title>
            <description>Patients with any cancer type who are planned to initiate standard of care (SOC) anti-PD-1 or anti-PD-L1 treatment (Cohort 2).</description>
          </group>
        </group_list>
        <measure>
          <title>Change Between Pre-treatment and Post-treatment SUVmax (Standardized Uptake Values) in the Primary and/or Metastatic Tumor(s) on Whole-body [18F]F-AraG Positron Emission Tomography/Magnetic Resonance (PET/MR) Imaging by Study Cohort.</title>
          <description>The nonparametric paired Wilcoxon Signed-rank test will be used to assess differences in SUVmax before and after treatment. The log2 ratio of post-treatment versus baseline SUVmax within the tumor and lymphoid tissues will also be calculated</description>
          <population>SUVmax data not collected</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Compare Change in SUVmax of the Primary Tumor in Patients Who Achieve Pathologic Downstaging or Clinical Response and Those Without Pathologic or Clinical Response at Time of Surgery in Patients Receiving Neoadjuvant Atezolizumab (Cohort 1)</title>
        <description>To correlate change in SUVmax to clinical and/or pathologic response, patients will be divided into two groups: those who achieved clinical response and/or pathologic downs-staging, and those who did not. The median and interquartile range of change in SUVmax from baseline to pre-surgery in the different groups will be descriptively reported. For Cohort 1, clinical response will be determined by abdominal imaging performed &lt;30 days after the last dose of atezolizumab prior to cystectomy compared to baseline pre-treatment imaging using RECIST v1.1 criteria, as specified in the companion treatment protocol. For Cohort 1, pathologic response will be determined by evidence of down-staging (e.g. from muscle invasive to non-muscle invasive, or complete pathologic response) at the time of cystectomy.</description>
        <time_frame>Up to 6 weeks</time_frame>
        <population>SUVmax data not collected</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Neoadjuvant</title>
            <description>Patients with localized bladder cancer who are eligible for the UCSF phase 2 clinical trial of neoadjuvant atezolizumab before definitive surgery (NCT02451423) (Cohort 1). For the neoadjuvant cohort, study participants will undergo whole body PET/MR imaging with [18F]F-AraG within 7 days of initiating atezolizumab and within 7 days before surgery. Approximately 12 patients will be enrolled.&#xD;
Fluorine F 18 Ara-G: Given IV&#xD;
Positron Emission Tomography: Undergo PET/MR imaging&#xD;
Magnetic Resonance Imaging: Undergo PET/MR imaging</description>
          </group>
        </group_list>
        <measure>
          <title>Compare Change in SUVmax of the Primary Tumor in Patients Who Achieve Pathologic Downstaging or Clinical Response and Those Without Pathologic or Clinical Response at Time of Surgery in Patients Receiving Neoadjuvant Atezolizumab (Cohort 1)</title>
          <description>To correlate change in SUVmax to clinical and/or pathologic response, patients will be divided into two groups: those who achieved clinical response and/or pathologic downs-staging, and those who did not. The median and interquartile range of change in SUVmax from baseline to pre-surgery in the different groups will be descriptively reported. For Cohort 1, clinical response will be determined by abdominal imaging performed &lt;30 days after the last dose of atezolizumab prior to cystectomy compared to baseline pre-treatment imaging using RECIST v1.1 criteria, as specified in the companion treatment protocol. For Cohort 1, pathologic response will be determined by evidence of down-staging (e.g. from muscle invasive to non-muscle invasive, or complete pathologic response) at the time of cystectomy.</description>
          <population>SUVmax data not collected</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change Between Pre-treatment and Post-treatment SUVmax in Lymphoid Organs on Whole-body [18F]F-AraG PET/MR Imaging (Cohort 1 and 2)</title>
        <time_frame>Up to 8 days</time_frame>
        <population>SUVmax data not collected</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1: Neoadjuvant</title>
            <description>Patients with localized bladder cancer who are eligible for the University of California, San Francisco (UCSF) phase 2 clinical trial of neoadjuvant atezolizumab before definitive surgery (NCT02451423) (Cohort 1).</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: Standard of Care (SOC)</title>
            <description>Patients with any cancer type who are planned to initiate standard of care (SOC) anti-PD-1 or anti-PD-L1 treatment (Cohort 2).</description>
          </group>
        </group_list>
        <measure>
          <title>Change Between Pre-treatment and Post-treatment SUVmax in Lymphoid Organs on Whole-body [18F]F-AraG PET/MR Imaging (Cohort 1 and 2)</title>
          <population>SUVmax data not collected</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Patients were evaluated one day and one week via telephone visit after each radiopharmaceutical injection for safety follow-up, up to 6 weeks.</time_frame>
      <desc>No patients were enrolled in Cohort 1. All patients who receive any dose of [18F]F-AraG were analyzed for safety, all adverse events were recorded. Patients removed from study for unacceptable treatment related adverse event(s) were followed until resolution or stabilization of all treatment related adverse events (AE) to Grade 0-1.</desc>
      <group_list>
        <group group_id="E1">
          <title>Cohort 2: Standard of Care (SOC)</title>
          <description>Patients with any cancer type who are planned to initiate standard of care (SOC) anti-PD-1 or anti-PD-L1 treatment.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Hematuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>This study was terminated due to low accrual. Only four participants were accrued to Cohort 2 (SOC) for this protocol. No patients were enrolled for cohort 1.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Lawrence Fong</name_or_title>
      <organization>University of California, San Francisco</organization>
      <phone>(415) 353-2051</phone>
      <email>Lawrence.Fong@ucsf.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03007719
org study id: 16709
secondary id: NCI-2017-01323
nct id: NCT03007719
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies how well fluorine F 18 Ara-G positron emission tomography
      (PET)/magnetic resonance (MR) imaging works in measuring clinical response to atezolizumab or
      patients with cancer receiving standard of care Anti-PD-1/L1. Diagnostic procedures, such as
      fluorine F 18 Ara-G PET/MR imaging, may help measure a patient's response to standard of care
      atezolizumab or Anti-PD-1/L1 treatment.
PRIMARY OBJECTIVES:

      I. To assess the change in fluorine F 18 Ara-G ([18F]F-AraG) uptake in primary and/or
      metastatic tumor(s) on whole-body [18F]F-AraG PET/MR imaging associated with neoadjuvant
      atezolizumab and standard of care (SOC) anti-PD-1 or anti-PD-L1 treatment.

      SECONDARY OBJECTIVES:

      I. To correlate change in [18F]F-AraG uptake within the primary tumor with clinical and
      pathologic response in patients treated with neoadjuvant atezolizumab. (Cohort 1) II. To
      assess [18F]F-AraG uptake in lymphoid organs before and after anti-PD-1 or anti-PD-L1
      treatment. (Cohort 1 and 2)

      OUTLINE: Patients are assigned to 1 or 2 cohorts.

      COHORT I (NEOADJUVANT COHORT): Patients receive fluorine F 18 Ara-G intravenously (IV) and
      undergo PET/MR imaging over 1.5-3 hours within 7 days of starting standard of care
      atezolizumab and within 7 days before surgery.

      COHORT II (SOC COHORT): Patients receive fluorine F 18 Ara-G IV and undergo PET/MR imaging
      over 1.5-3 hours within 7 days of initiating course 1 of anti-PD-1 or anti-PD-L1 therapy and
      between day 15 of course 1 and day 7 of course 2 of anti-PD-1 or anti-PD-L1 treatment.

      After completion of study, patients are followed up at days 2 and 8.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Change Between Pre-treatment and Post-treatment SUVmax (Standardized Uptake Values) in the Primary and/or Metastatic Tumor(s) on Whole-body [18F]F-AraG Positron Emission Tomography/Magnetic Resonance (PET/MR) Imaging by Study Cohort.
time frame: Up to 2 weeks
description: The nonparametric paired Wilcoxon Signed-rank test will be used to assess differences in SUVmax before and after treatment. The log2 ratio of post-treatment versus baseline SUVmax within the tumor and lymphoid tissues will also be calculated
measure: Compare Change in SUVmax of the Primary Tumor in Patients Who Achieve Pathologic Downstaging or Clinical Response and Those Without Pathologic or Clinical Response at Time of Surgery in Patients Receiving Neoadjuvant Atezolizumab (Cohort 1)
time frame: Up to 6 weeks
description: To correlate change in SUVmax to clinical and/or pathologic response, patients will be divided into two groups: those who achieved clinical response and/or pathologic downs-staging, and those who did not. The median and interquartile range of change in SUVmax from baseline to pre-surgery in the different groups will be descriptively reported. For Cohort 1, clinical response will be determined by abdominal imaging performed <30 days after the last dose of atezolizumab prior to cystectomy compared to baseline pre-treatment imaging using RECIST v1.1 criteria, as specified in the companion treatment protocol. For Cohort 1, pathologic response will be determined by evidence of down-staging (e.g. from muscle invasive to non-muscle invasive, or complete pathologic response) at the time of cystectomy.
measure: Change Between Pre-treatment and Post-treatment SUVmax in Lymphoid Organs on Whole-body [18F]F-AraG PET/MR Imaging (Cohort 1 and 2)
time frame: Up to 8 days
arm group label: Cohort 1: Neoadjuvant
arm group type: Experimental
description: Patients with localized bladder cancer who are eligible for the UCSF phase 2 clinical trial of neoadjuvant atezolizumab before definitive surgery (NCT02451423) (Cohort 1). For the neoadjuvant cohort, study participants will undergo whole body PET/MR imaging with [18F]F-AraG within 7 days of initiating atezolizumab and within 7 days before surgery. Approximately 12 patients will be enrolled.
arm group label: Cohort 2: Standard of Care (SOC)
arm group type: Experimental
description: Patients with any cancer type who are planned to initiate standard of care (SOC) anti-PD-1 or anti-PD-L1 treatment (Cohort 2). For the SOC cohort, study participants will undergo whole body PET/MR imaging with [18F]F-AraG within 7 days of initiating Cycle 1 anti-PD-1 or anti-PD-L1, and between Cycle 1 Day 15 (C1D15) and Cycle 2 Day 7 (C2D7) anti-PD-1 or anti-PD-L1. Approximately 19 patients will be enrolled.
intervention type: Drug
intervention name: Fluorine F 18 Ara-G
description: Given IV
arm group label: Cohort 1: Neoadjuvant
arm group label: Cohort 2: Standard of Care (SOC)
other name: 2'-deoxy-2'-fluoro-9-β-D-arabinofuranosylguanine
other name: VisAcT
intervention type: Procedure
intervention name: Positron Emission Tomography
description: Undergo PET/MR imaging
arm group label: Cohort 1: Neoadjuvant
arm group label: Cohort 2: Standard of Care (SOC)
other name: PET
other name: PET Scan
intervention type: Procedure
intervention name: Magnetic Resonance Imaging
description: Undergo PET/MR imaging
arm group label: Cohort 1: Neoadjuvant
arm group label: Cohort 2: Standard of Care (SOC)
other name: MRI
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Lawrence Fong, MD
role: Principal Investigator
affiliation: University of California, San Francisco
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of California, San Francisco
investigator full name: Lawrence Fong
investigator title: Professor in Residence
mesh term: Carcinoma, Transitional Cell
mesh term: Fluorides
sharing ipd: Undecided
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: This study was terminated due to low accrual. Only four participants were accrued to Cohort 2 (SOC) for this protocol. No patients were enrolled for cohort 1.
point of contact: 