<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/NCT04410367</url>
  </required_header>
  <id_info>
    <org_study_id>BED-FLC-219</org_study_id>
    <nct_id>NCT04410367</nct_id>
  </id_info>
  <brief_title>Study to Establish Image Interpretation Criteria for 18F Fluciclovine PET in Detecting Recurrent Brain Metastases (PURSUE)</brief_title>
  <acronym>PURSUE</acronym>
  <official_title>An Open-label, Single-arm, Single-dose, Prospective, Multicenter Phase 2b Study to Establish Image Interpretation Criteria for 18F-Fluciclovine Positron Emission Tomography (PET) in Detecting Recurrent Brain Metastases After Radiation Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Blue Earth Diagnostics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Precision For Medicine</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Blue Earth Diagnostics</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      An Open-label, Single-arm, Single-dose, Prospective, Multicenter Phase 2b Study to Establish&#xD;
      Image Interpretation Criteria for 18F-Fluciclovine Positron Emission Tomography (PET) in&#xD;
      Detecting Recurrent Brain Metastases After Radiation Therapy&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 31, 2020</start_date>
  <completion_date type="Actual">December 31, 2021</completion_date>
  <primary_completion_date type="Actual">December 31, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Positron Emission Tomography (PET) Imaging study</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases at Different Visual Thresholds</measure>
    <time_frame>60 days</time_frame>
    <description>Sensitivity is calculated as % of participants with positive histopathology who are classified as positive on their 18F fluciclovine PET (i.e. true positive). Each participant had one lesion, therefore results are representative of both subject and lesion level sensitivity.&#xD;
Three readers evaluated the PET scans to classify 18F fluciclovine uptake in study lesions according to 4 incremental categories: absent, mild, moderate or marked. Three different thresholds of 18F fluciclovine uptake were then applied to calculate the sensitivity: Mild or Higher Uptake, Moderate or Higher Uptake, Marked Uptake. As an example, for calculating sensitivity based on the threshold of Mild or Higher Uptake, all participants with positive histopathology, classified by a reader as having mild, moderate or marked 18F fluciclovine uptake, would be categorized as true positive. This calculation was then repeated on the other two threshold categories, to produce sensitivities at different thresholds.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Specificity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases at Different Visual Thresholds</measure>
    <time_frame>60 days</time_frame>
    <description>Specificity is calculated as the % of participants with negative histopathology who are classified as negative on their 18F fluciclovine PET (i.e. true negative). Each participant had 1 lesion, therefore results are representative of both subject and lesion level specificity. 3 readers evaluated the PET scans to classify 18F fluciclovine uptake in study lesions according to 4 incremental categories: absent, mild, moderate or marked. 3 different thresholds of uptake were then applied to calculate the specificity: Mild or Higher Uptake, Moderate or Higher Uptake, Marked Uptake. Example, for calculating specificity based on the threshold of Moderate or Higher Uptake, all participants with negative histopath, classified by a reader as having absent or mild uptake (i.e. not classified by a reader as having moderate or marked uptake), would be categorized as true negative. This calculation was repeated on the other 2 threshold categories, to produce specificities at different thresholds</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases Based on Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake</measure>
    <time_frame>60 days</time_frame>
    <description>Sensitivity calculated as %participants with positive histopath and positive on PET (i.e. true positive). Each participant had 1 lesion, results represent both subject and lesion level sensitivity. Sensitivity is calculated using positive PET classified by quantitative and dynamic measures. Quantitative measure is based on lesion standardized uptake value (SUV). Receiver Operating Characteristic (ROC) analysis of all participant lesion SUV was performed. ROC analyses was performed to select a SUV threshold for calculating sensitivity. Sensitivity calculation: participants with positive histopath and SUV = or &gt; threshold are positive on scan. Dynamic measure: 3 readers evaluated PET scans to classify uptake pattern based on 4 categories: Type 0, Type I, Type II, Type III. Sensitivity is calculated for each type of uptake pattern (example: calculating sensitivity based on Type I pattern, participants with positive histopath, classified as Type I, would be categorized as true positive).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Specificity of Different Thresholds of Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake.</measure>
    <time_frame>60 days</time_frame>
    <description>Specificity is calculated as %participants with negative histopath and negative on PET (i.e. true negative). Each participant had 1 lesion, results represent both subject and lesion level specificity. Specificity is calculated using negative PET classified by quantitative and dynamic measures. Quantitative measure is based on lesion standardized uptake value (SUV). Receiver Operating Characteristic (ROC) analysis of all participant lesion SUV was performed. ROC analyses was performed to select a SUV threshold for calculating sensitivity. Specificity calculation: participants with negative histopath, SUV &lt; threshold are negative on scan. Dynamic measure: 3 readers evaluated PET scans to classify uptake pattern based on 4 categories: Type 0, Type I, Type II, Type III. Specificity is calculated for each type of uptake pattern (example, calculating specificity based on Type I pattern, participants with negative histopath, classified as Type I, would be categorized as true negative)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment-emergent Adverse Events</measure>
    <time_frame>From the time of administration of 18F fluciclovine until 1 day post-18F-fluciclovine administration.</time_frame>
    <description>Safety will be assessed from data on the occurrence of one or more treatment-emergent Adverse Events from the time of intravenous administration of 18F fluciclovine until 1 day post-18F-fluciclovine administration.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">23</enrollment>
  <condition>Brain Metastases</condition>
  <arm_group>
    <arm_group_label>Patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single intravenous administration of 18F fluciclovine for PET Scan</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>18F fluciclovine</intervention_name>
    <description>18F fluciclovine injection, 185 MegaBecquerel (MBq) (5 Millicurie (mCi)) ± 20%, delivered as an intravenous bolus</description>
    <arm_group_label>Patients</arm_group_label>
    <other_name>Axumin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2&#xD;
&#xD;
          2. Previous history of solid tumor brain metastasis of any origin&#xD;
&#xD;
          3. Histopathological confirmation of the primary solid tumor or a metastatic site&#xD;
&#xD;
          4. Previous radiation therapy of brain metastatic lesion(s)&#xD;
&#xD;
          5. A reference lesion considered by the site investigator to be equivocal for recurrent&#xD;
             brain metastasis&#xD;
&#xD;
          6. Patient requires further confirmatory diagnostic procedures to confirm brain MRI&#xD;
             findings and is planned for craniotomy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        1. Patients with a history of active hematological malignancy&#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>Eugene Teoh, MD</last_name>
    <role>Study Director</role>
    <affiliation>Blue Earth Diagnostics</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Rupesh Kotecha, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Miami Cancer Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>John Wayne Cancer Institute at Providence St. John's Health Center</name>
      <address>
        <city>Santa Monica</city>
        <state>California</state>
        <zip>90404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yale School of Medicine</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06519</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Miami Cancer Institute</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33176</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ochsner Clinic Foundation</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70131</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine Center for Clinical Imaging Research</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NYU Langone Health</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Cleveland</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania Health System</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Center for Quantitative Cancer Imaging at Huntsman Cancer Institute</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>May 27, 2020</study_first_submitted>
  <study_first_submitted_qc>May 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 1, 2020</study_first_posted>
  <results_first_submitted>December 29, 2022</results_first_submitted>
  <results_first_submitted_qc>July 11, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">August 1, 2023</results_first_posted>
  <last_update_submitted>July 11, 2023</last_update_submitted>
  <last_update_submitted_qc>July 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Recurrent Brain Metastases</keyword>
  <keyword>Diagnostic</keyword>
  <keyword>Positron Emission Tomography (PET) Scan</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Brain Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 10, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/67/NCT04410367/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 1, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/67/NCT04410367/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Subjects with a history of brain metastases previously treated with primary, adjuvant, or repeat (salvage) radiation therapy, with a recent standard of care (SoC) brain magnetic resonance imaging (MRI) found to be equivocal for recurrent brain metastasis, and who met all the inclusion criteria and none of the exclusion criteria, were consented and enrolled.&#xD;
Subjects were screened between 28Oct2020 and 30Dec2021. Nine clinical research sites in the US participated in the study.</recruitment_details>
      <pre_assignment_details>On-study site investigators prospectively annotated and measured the 'reference lesion' on a postradiation treatment MRI scan and on the SoC MRI brain scan to confirm eligibility. The 'reference lesion' was defined as the lesion which was Equivocal for recurrent metastasis on SoC MRI, Intended for pre-planned SoC craniotomy, and If &gt; 1 equivocal lesion was intended for resection, the largest of these lesions.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>18F-Fluciclovine Injection</title>
          <description>Subjects who have been dosed with 18F-Fluciclovine, have an evaluable on-study PET scan, and an evaluable central histopathology report from the sample obtained from the SoC craniotomy.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="23"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Underwent 18F-fluciclovine PET</title>
              <participants_list>
                <participants group_id="P1" count="23"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="23"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Patients</title>
          <description>Single intravenous administration of 18F fluciclovine for PET Scan&#xD;
18F fluciclovine: 18F fluciclovine injection, 185 MBq (5 mCi) ± 20%, delivered as an intravenous bolus</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="23"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="59.8" spread="11.88"/>
                  </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="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </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="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" 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_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" 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="B1" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases at Different Visual Thresholds</title>
        <description>Sensitivity is calculated as % of participants with positive histopathology who are classified as positive on their 18F fluciclovine PET (i.e. true positive). Each participant had one lesion, therefore results are representative of both subject and lesion level sensitivity.&#xD;
Three readers evaluated the PET scans to classify 18F fluciclovine uptake in study lesions according to 4 incremental categories: absent, mild, moderate or marked. Three different thresholds of 18F fluciclovine uptake were then applied to calculate the sensitivity: Mild or Higher Uptake, Moderate or Higher Uptake, Marked Uptake. As an example, for calculating sensitivity based on the threshold of Mild or Higher Uptake, all participants with positive histopathology, classified by a reader as having mild, moderate or marked 18F fluciclovine uptake, would be categorized as true positive. This calculation was then repeated on the other two threshold categories, to produce sensitivities at different thresholds.</description>
        <time_frame>60 days</time_frame>
        <population>Sensitivity analysis (%) based on 10 subjects with positive lesions per standard of truth (central histopathological analysis).</population>
        <group_list>
          <group group_id="O1">
            <title>18F-Fluciclovine Injection</title>
            <description>Subjects who have been dosed with 18F-Fluciclovine, have an evaluable on-study PET scan, and positive histopathology.</description>
          </group>
        </group_list>
        <measure>
          <title>Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases at Different Visual Thresholds</title>
          <description>Sensitivity is calculated as % of participants with positive histopathology who are classified as positive on their 18F fluciclovine PET (i.e. true positive). Each participant had one lesion, therefore results are representative of both subject and lesion level sensitivity.&#xD;
Three readers evaluated the PET scans to classify 18F fluciclovine uptake in study lesions according to 4 incremental categories: absent, mild, moderate or marked. Three different thresholds of 18F fluciclovine uptake were then applied to calculate the sensitivity: Mild or Higher Uptake, Moderate or Higher Uptake, Marked Uptake. As an example, for calculating sensitivity based on the threshold of Mild or Higher Uptake, all participants with positive histopathology, classified by a reader as having mild, moderate or marked 18F fluciclovine uptake, would be categorized as true positive. This calculation was then repeated on the other two threshold categories, to produce sensitivities at different thresholds.</description>
          <population>Sensitivity analysis (%) based on 10 subjects with positive lesions per standard of truth (central histopathological analysis).</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Mild or Higher Uptake = Positive : Central Reader 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100" lower_limit="69.2" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mild or Higher Uptake = Positive : Central Reader 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100" lower_limit="69.2" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mild or Higher Uptake = Positive : Central Reader 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100" lower_limit="69.2" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Moderate or Higher Uptake = Positive : Central Reader 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100" lower_limit="69.2" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Moderate or Higher Uptake = Positive : Central Reader 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100" lower_limit="69.2" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Moderate or Higher Uptake = Positive : Central Reader 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="90" lower_limit="55.5" upper_limit="99.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Marked Uptake = Positive : Central Reader 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80" lower_limit="44.4" upper_limit="97.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Marked Uptake = Positive : Central Reader 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40" lower_limit="12.2" upper_limit="73.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Marked Uptake = Positive : Central Reader 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60" lower_limit="26.2" upper_limit="87.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Specificity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases at Different Visual Thresholds</title>
        <description>Specificity is calculated as the % of participants with negative histopathology who are classified as negative on their 18F fluciclovine PET (i.e. true negative). Each participant had 1 lesion, therefore results are representative of both subject and lesion level specificity. 3 readers evaluated the PET scans to classify 18F fluciclovine uptake in study lesions according to 4 incremental categories: absent, mild, moderate or marked. 3 different thresholds of uptake were then applied to calculate the specificity: Mild or Higher Uptake, Moderate or Higher Uptake, Marked Uptake. Example, for calculating specificity based on the threshold of Moderate or Higher Uptake, all participants with negative histopath, classified by a reader as having absent or mild uptake (i.e. not classified by a reader as having moderate or marked uptake), would be categorized as true negative. This calculation was repeated on the other 2 threshold categories, to produce specificities at different thresholds</description>
        <time_frame>60 days</time_frame>
        <population>Specificity analysis (%) based on 13 subjects with negative lesions per standard of truth (central histopathological analysis).</population>
        <group_list>
          <group group_id="O1">
            <title>18F-Fluciclovine Injection</title>
            <description>Subjects who have been dosed with 18F-Fluciclovine, have an evaluable on-study PET scan, and negative histopathology.</description>
          </group>
        </group_list>
        <measure>
          <title>Specificity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases at Different Visual Thresholds</title>
          <description>Specificity is calculated as the % of participants with negative histopathology who are classified as negative on their 18F fluciclovine PET (i.e. true negative). Each participant had 1 lesion, therefore results are representative of both subject and lesion level specificity. 3 readers evaluated the PET scans to classify 18F fluciclovine uptake in study lesions according to 4 incremental categories: absent, mild, moderate or marked. 3 different thresholds of uptake were then applied to calculate the specificity: Mild or Higher Uptake, Moderate or Higher Uptake, Marked Uptake. Example, for calculating specificity based on the threshold of Moderate or Higher Uptake, all participants with negative histopath, classified by a reader as having absent or mild uptake (i.e. not classified by a reader as having moderate or marked uptake), would be categorized as true negative. This calculation was repeated on the other 2 threshold categories, to produce specificities at different thresholds</description>
          <population>Specificity analysis (%) based on 13 subjects with negative lesions per standard of truth (central histopathological analysis).</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Mild or Higher Uptake = Positive : Central Reader 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0.0" upper_limit="24.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mild or Higher Uptake = Positive : Central Reader 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0.0" upper_limit="24.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mild or Higher Uptake = Positive : Central Reader 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0.0" upper_limit="24.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Moderate or Higher Uptake = Positive : Central Reader 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38.5" lower_limit="13.9" upper_limit="68.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Moderate or Higher Uptake = Positive : Central Reader 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30.8" lower_limit="9.1" upper_limit="61.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Moderate or Higher Uptake = Positive : Central Reader 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.2" lower_limit="19.2" upper_limit="74.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Marked Uptake = Positive : Central Reader 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="92.3" lower_limit="64.0" upper_limit="99.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Marked Uptake = Positive : Central Reader 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100" lower_limit="75.3" upper_limit="100.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Marked Uptake = Positive : Central Reader 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100" lower_limit="75.3" upper_limit="100.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases Based on Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake</title>
        <description>Sensitivity calculated as %participants with positive histopath and positive on PET (i.e. true positive). Each participant had 1 lesion, results represent both subject and lesion level sensitivity. Sensitivity is calculated using positive PET classified by quantitative and dynamic measures. Quantitative measure is based on lesion standardized uptake value (SUV). Receiver Operating Characteristic (ROC) analysis of all participant lesion SUV was performed. ROC analyses was performed to select a SUV threshold for calculating sensitivity. Sensitivity calculation: participants with positive histopath and SUV = or &gt; threshold are positive on scan. Dynamic measure: 3 readers evaluated PET scans to classify uptake pattern based on 4 categories: Type 0, Type I, Type II, Type III. Sensitivity is calculated for each type of uptake pattern (example: calculating sensitivity based on Type I pattern, participants with positive histopath, classified as Type I, would be categorized as true positive).</description>
        <time_frame>60 days</time_frame>
        <population>Sensitivity analysis (%) based on 10 subjects with positive lesions per standard of truth.</population>
        <group_list>
          <group group_id="O1">
            <title>18F-Fluciclovine Injection</title>
            <description>Subjects who have been dosed with 18F-Fluciclovine, have an evaluable on-study PET scan, and positive histopathology</description>
          </group>
        </group_list>
        <measure>
          <title>Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases Based on Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake</title>
          <description>Sensitivity calculated as %participants with positive histopath and positive on PET (i.e. true positive). Each participant had 1 lesion, results represent both subject and lesion level sensitivity. Sensitivity is calculated using positive PET classified by quantitative and dynamic measures. Quantitative measure is based on lesion standardized uptake value (SUV). Receiver Operating Characteristic (ROC) analysis of all participant lesion SUV was performed. ROC analyses was performed to select a SUV threshold for calculating sensitivity. Sensitivity calculation: participants with positive histopath and SUV = or &gt; threshold are positive on scan. Dynamic measure: 3 readers evaluated PET scans to classify uptake pattern based on 4 categories: Type 0, Type I, Type II, Type III. Sensitivity is calculated for each type of uptake pattern (example: calculating sensitivity based on Type I pattern, participants with positive histopath, classified as Type I, would be categorized as true positive).</description>
          <population>Sensitivity analysis (%) based on 10 subjects with positive lesions per standard of truth.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Quantitative SUV ≥ 4.8 = Positive : Central Reader 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80" lower_limit="44.4" upper_limit="97.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Quantitative SUV ≥ 4.8 = Positive : Central Reader 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80" lower_limit="44.4" upper_limit="97.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Quantitative SUV ≥ 4.8 = Positive : Central Reader 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80" lower_limit="44.4" upper_limit="97.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dynamic Type 0: Central Reader 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="30.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dynamic Type 0 : Central Reader 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="30.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dynamic Type 0 : Central Reader 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="30.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dynamic Type I: Central Reader 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80" lower_limit="44.4" upper_limit="97.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dynamic Type I: Central Reader 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="90" lower_limit="55.5" upper_limit="99.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dynamic Type I: Central Reader 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100" lower_limit="69.2" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dynamic Type II: Central Reader 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10" lower_limit="0.3" upper_limit="44.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dynamic Type II: Central Reader 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10" lower_limit="0.3" upper_limit="44.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dynamic Type II: Central Reader 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="30.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dynamic Type III: Central Reader 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10" lower_limit="0.3" upper_limit="44.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dynamic Type III: Central Reader 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="30.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dynamic Type III: Central Reader 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="30.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Specificity of Different Thresholds of Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake.</title>
        <description>Specificity is calculated as %participants with negative histopath and negative on PET (i.e. true negative). Each participant had 1 lesion, results represent both subject and lesion level specificity. Specificity is calculated using negative PET classified by quantitative and dynamic measures. Quantitative measure is based on lesion standardized uptake value (SUV). Receiver Operating Characteristic (ROC) analysis of all participant lesion SUV was performed. ROC analyses was performed to select a SUV threshold for calculating sensitivity. Specificity calculation: participants with negative histopath, SUV &lt; threshold are negative on scan. Dynamic measure: 3 readers evaluated PET scans to classify uptake pattern based on 4 categories: Type 0, Type I, Type II, Type III. Specificity is calculated for each type of uptake pattern (example, calculating specificity based on Type I pattern, participants with negative histopath, classified as Type I, would be categorized as true negative)</description>
        <time_frame>60 days</time_frame>
        <population>Subjects who have been dosed with 18F-Fluciclovine, have an evaluable on-study PET scan, and negative histopathology.</population>
        <group_list>
          <group group_id="O1">
            <title>18F-Fluciclovine Injection</title>
            <description>Specificity of 18F fluciclovine PET for detecting recurrent brain metastases based on quantitative and dynamic measures of lesion 18F fluciclovine uptake</description>
          </group>
        </group_list>
        <measure>
          <title>Specificity of Different Thresholds of Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake.</title>
          <description>Specificity is calculated as %participants with negative histopath and negative on PET (i.e. true negative). Each participant had 1 lesion, results represent both subject and lesion level specificity. Specificity is calculated using negative PET classified by quantitative and dynamic measures. Quantitative measure is based on lesion standardized uptake value (SUV). Receiver Operating Characteristic (ROC) analysis of all participant lesion SUV was performed. ROC analyses was performed to select a SUV threshold for calculating sensitivity. Specificity calculation: participants with negative histopath, SUV &lt; threshold are negative on scan. Dynamic measure: 3 readers evaluated PET scans to classify uptake pattern based on 4 categories: Type 0, Type I, Type II, Type III. Specificity is calculated for each type of uptake pattern (example, calculating specificity based on Type I pattern, participants with negative histopath, classified as Type I, would be categorized as true negative)</description>
          <population>Subjects who have been dosed with 18F-Fluciclovine, have an evaluable on-study PET scan, and negative histopathology.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>SUV ≥ 4.8 : Central Reader 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="84.6" lower_limit="54.6" upper_limit="98.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SUV ≥ 4.8 : Central Reader 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="84.6" lower_limit="54.6" upper_limit="98.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SUV ≥ 4.8 : Central Reader 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="84.6" lower_limit="54.6" upper_limit="98.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dynamic Type 0 : Central Reader 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100" lower_limit="75.3" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dynamic Type 0 : Central Reader 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100" lower_limit="75.3" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dynamic Type 0 : Central Reader 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100" lower_limit="75.3" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dynamic Type I : Central Reader 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.7" lower_limit="0.2" upper_limit="36.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dynamic Type I : Central Reader 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.4" lower_limit="1.9" upper_limit="45.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dynamic Type I : Central Reader 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="24.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dynamic Type II : Central Reader 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="92.3" lower_limit="64.0" upper_limit="99.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dynamic Type II : Central Reader 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="84.6" lower_limit="54.6" upper_limit="98.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dynamic Type II : Central Reader 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100" lower_limit="75.3" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dynamic Type III : Central Reader 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100" lower_limit="75.3" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dynamic Type III : Central Reader 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100" lower_limit="75.3" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dynamic Type III : Central Reader 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100" lower_limit="75.3" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Treatment-emergent Adverse Events</title>
        <description>Safety will be assessed from data on the occurrence of one or more treatment-emergent Adverse Events from the time of intravenous administration of 18F fluciclovine until 1 day post-18F-fluciclovine administration.</description>
        <time_frame>From the time of administration of 18F fluciclovine until 1 day post-18F-fluciclovine administration.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>18F-Fluciclovine Injection</title>
            <description>Safety will be assessed from data on the occurrence of one or more treatment-emergent Adverse Events from the time of intravenous administration of 18F fluciclovine until 2 days post-18F-fluciclovine administration.</description>
          </group>
        </group_list>
        <measure>
          <title>Treatment-emergent Adverse Events</title>
          <description>Safety will be assessed from data on the occurrence of one or more treatment-emergent Adverse Events from the time of intravenous administration of 18F fluciclovine until 1 day post-18F-fluciclovine administration.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Subjects reporting at least 1 TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nervous System Disorders (Headache)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Safety was assessed from the time of 18F-fluciclovine administration until 1 day post18Ffluciclovine administration based on reported adverse events (AEs) and serious adverse events (SAEs); treatment emergent adverse events (TEAE).</time_frame>
      <group_list>
        <group group_id="E1">
          <title>18F-Fluciclovine Injection</title>
          <description>Subjects who have been dosed with 18F-Fluciclovine, have an evaluable on-study PET scan, and an evaluable central histopathology report from the sample obtained from the SoC craniotomy.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>Neither the INSTITUTION nor the INVESTIGATOR will submit for publication or public disclosure any publication or disclosure based on the results of the Study until after the first to occur of (a) publication of the multi-center clinical trial results; (b) notification by BED that the multi-center clinical trial submission is no longer planned; or (c) the eighteen (18) month anniversary of the completion or early termination of the multi-center clinical trial.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Chief Medical Officer</name_or_title>
      <organization>Blue Earth Diagnostics, Ltd.</organization>
      <phone>+44 (0)1865 784 186</phone>
      <email>contact@blueearthDx.com</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/NCT04410367
org study id: BED-FLC-219
nct id: NCT04410367
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
An Open-label, Single-arm, Single-dose, Prospective, Multicenter Phase 2b Study to Establish
      Image Interpretation Criteria for 18F-Fluciclovine Positron Emission Tomography (PET) in
      Detecting Recurrent Brain Metastases After Radiation Therapy
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Positron Emission Tomography (PET) Imaging study
primary purpose: Diagnostic
masking: None (Open Label)
measure: Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases at Different Visual Thresholds
time frame: 60 days
description: Sensitivity is calculated as % of participants with positive histopathology who are classified as positive on their 18F fluciclovine PET (i.e. true positive). Each participant had one lesion, therefore results are representative of both subject and lesion level sensitivity.
Three readers evaluated the PET scans to classify 18F fluciclovine uptake in study lesions according to 4 incremental categories: absent, mild, moderate or marked. Three different thresholds of 18F fluciclovine uptake were then applied to calculate the sensitivity: Mild or Higher Uptake, Moderate or Higher Uptake, Marked Uptake. As an example, for calculating sensitivity based on the threshold of Mild or Higher Uptake, all participants with positive histopathology, classified by a reader as having mild, moderate or marked 18F fluciclovine uptake, would be categorized as true positive. This calculation was then repeated on the other two threshold categories, to produce sensitivities at different thresholds.
measure: Specificity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases at Different Visual Thresholds
time frame: 60 days
description: Specificity is calculated as the % of participants with negative histopathology who are classified as negative on their 18F fluciclovine PET (i.e. true negative). Each participant had 1 lesion, therefore results are representative of both subject and lesion level specificity. 3 readers evaluated the PET scans to classify 18F fluciclovine uptake in study lesions according to 4 incremental categories: absent, mild, moderate or marked. 3 different thresholds of uptake were then applied to calculate the specificity: Mild or Higher Uptake, Moderate or Higher Uptake, Marked Uptake. Example, for calculating specificity based on the threshold of Moderate or Higher Uptake, all participants with negative histopath, classified by a reader as having absent or mild uptake (i.e. not classified by a reader as having moderate or marked uptake), would be categorized as true negative. This calculation was repeated on the other 2 threshold categories, to produce specificities at different thresholds
measure: Sensitivity of 18F Fluciclovine PET for Detecting Recurrent Brain Metastases Based on Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake
time frame: 60 days
description: Sensitivity calculated as %participants with positive histopath and positive on PET (i.e. true positive). Each participant had 1 lesion, results represent both subject and lesion level sensitivity. Sensitivity is calculated using positive PET classified by quantitative and dynamic measures. Quantitative measure is based on lesion standardized uptake value (SUV). Receiver Operating Characteristic (ROC) analysis of all participant lesion SUV was performed. ROC analyses was performed to select a SUV threshold for calculating sensitivity. Sensitivity calculation: participants with positive histopath and SUV = or > threshold are positive on scan. Dynamic measure: 3 readers evaluated PET scans to classify uptake pattern based on 4 categories: Type 0, Type I, Type II, Type III. Sensitivity is calculated for each type of uptake pattern (example: calculating sensitivity based on Type I pattern, participants with positive histopath, classified as Type I, would be categorized as true positive).
measure: Specificity of Different Thresholds of Quantitative and Dynamic Measures of Lesion 18F Fluciclovine Uptake.
time frame: 60 days
description: Specificity is calculated as %participants with negative histopath and negative on PET (i.e. true negative). Each participant had 1 lesion, results represent both subject and lesion level specificity. Specificity is calculated using negative PET classified by quantitative and dynamic measures. Quantitative measure is based on lesion standardized uptake value (SUV). Receiver Operating Characteristic (ROC) analysis of all participant lesion SUV was performed. ROC analyses was performed to select a SUV threshold for calculating sensitivity. Specificity calculation: participants with negative histopath, SUV < threshold are negative on scan. Dynamic measure: 3 readers evaluated PET scans to classify uptake pattern based on 4 categories: Type 0, Type I, Type II, Type III. Specificity is calculated for each type of uptake pattern (example, calculating specificity based on Type I pattern, participants with negative histopath, classified as Type I, would be categorized as true negative)
measure: Treatment-emergent Adverse Events
time frame: From the time of administration of 18F fluciclovine until 1 day post-18F-fluciclovine administration.
description: Safety will be assessed from data on the occurrence of one or more treatment-emergent Adverse Events from the time of intravenous administration of 18F fluciclovine until 1 day post-18F-fluciclovine administration.
arm group label: Patients
arm group type: Experimental
description: Single intravenous administration of 18F fluciclovine for PET Scan
intervention type: Drug
intervention name: 18F fluciclovine
description: 18F fluciclovine injection, 185 MegaBecquerel (MBq) (5 Millicurie (mCi)) ± 20%, delivered as an intravenous bolus
arm group label: Patients
other name: Axumin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Eugene Teoh, MD
role: Study Director
affiliation: Blue Earth Diagnostics
last name: Rupesh Kotecha, MD
role: Principal Investigator
affiliation: Miami Cancer Institute
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Neoplasm Metastasis
mesh term: Brain Neoplasms
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 