<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/NCT04462419</url>
  </required_header>
  <id_info>
    <org_study_id>MC1975</org_study_id>
    <secondary_id>NCI-2020-04564</secondary_id>
    <secondary_id>MC1975</secondary_id>
    <nct_id>NCT04462419</nct_id>
  </id_info>
  <brief_title>18F-fluciclovine PET/MRI Imaging for the Detection of Tumor Recurrence After Radiation Injury to the Brain</brief_title>
  <official_title>18F-Fluciclovine PET Discrimination of Radiation Injury to the Brain</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Mayo Clinic</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I trial studies the ability and amount of fluciclovine positron emission&#xD;
      tomography (PET) imaging needed to recognize tumors that have come back (recurrence) after&#xD;
      brain injury from radiation therapy (radionecrosis) in patients with intracranial disease&#xD;
      that has spread to other places in the body (metastatic). F-18 fluciclovine is a radiotracer&#xD;
      that works by accumulating in tumor cells, making it easier to detect tumors. The results of&#xD;
      this study may also help investigators understand all the ways that F-18 fluciclovine may&#xD;
      affect patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To determine the static fluciclovine F18 (fluciclovine) PET imaging tumor-to-background&#xD;
      ratios (TBRmax; TBRmean) which distinguish true tumor recurrence from radionecrosis in&#xD;
      patients with intracranial metastatic disease previously treated with radiation therapy, and&#xD;
      magnetic resonance imaging (MRI) findings suggesting recurrent disease, using histopathology&#xD;
      as proof of disease.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To determine static fluciclovine PET standardized uptake value (SUV)peak, SUVmean values&#xD;
      and metabolic tumor volumes (MTV) which distinguish true tumor recurrence from radionecrosis&#xD;
      in patients with MRI findings suggesting recurrent disease, using serial MRI as a surrogate&#xD;
      marker of disease.&#xD;
&#xD;
      II. To determine early dynamic fluciclovine PET time activity curve values which distinguish&#xD;
      true tumor recurrence from radionecrosis in patients with MRI findings suggesting recurrent&#xD;
      disease, using histopathology or serial MRI as a marker of disease.&#xD;
&#xD;
      III. To correlate the determined static fluciclovine PET SUVpeak, SUVmean, TBRmax, TBRmean,&#xD;
      and MTV values with progression free survival.&#xD;
&#xD;
      IV. In patients with true tumor progression, SUV values will be correlated with Ki67 staining&#xD;
      on final pathology.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive fluciclovine intravenously (IV) and undergo brain dynamic PET/MRI imaging&#xD;
      over 50 minutes.&#xD;
&#xD;
      After completion of study, patients are followed up every 3 months for up to 1 year.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 18, 2020</start_date>
  <completion_date type="Anticipated">August 15, 2026</completion_date>
  <primary_completion_date type="Anticipated">August 15, 2025</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Tumor-to-background ratios (TBR)max and TBRmean thresholds</measure>
    <time_frame>Up to 4 weeks post study registration</time_frame>
    <description>Will be estimated to delineate tumor progression from radionecrosis for use in future studies. The optimal TBRmax and TBRmean thresholds will be chosen as the threshold with the best cutpoint/threshold during a Receiver Operating Characteristics analysis corresponding to the maximum area under the curve (AUC) value when both the sensitivity and specificity are greater than 85%.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Static values for fluciclovine PET standardized uptake value (SUV)peak that distinguish true tumor recurrence from radionecrosis in patients with MRI findings suggesting recurrent disease</measure>
    <time_frame>Up to 4 weeks post study registration</time_frame>
    <description>Determined using serial MRI as a surrogate marker of disease.The optimal SUVpeak, SUVmean and metabolic tumor volumes (MTV) values will be chosen as the threshold with the best cutpoint/threshold during a Receiver Operating Characteristics analysis corresponding to the maximum AUC value when both the sensitivity and specificity are greater than 85%.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Static values for fluciclovine SUVmean that distinguish true tumor recurrence from radionecrosis in patients with MRI findings suggesting recurrent disease</measure>
    <time_frame>Up to 4 weeks post study registration</time_frame>
    <description>Determined using serial MRI as a surrogate marker of disease. The optimal SUVmean values will be chosen as the threshold with the best cutpoint/threshold during a Receiver Operating Characteristics analysis corresponding to the maximum AUC value when both the sensitivity and specificity are greater than 85%.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Static values for metabolic tumor volumes (MTV) that distinguish true tumor recurrence from radionecrosis in patients with MRI findings suggesting recurrent disease</measure>
    <time_frame>Up to 4 weeks post study registration</time_frame>
    <description>Determined using serial MRI as a surrogate marker of disease. The optimal MTV values will be chosen as the threshold with the best cutpoint/threshold during a Receiver Operating Characteristics analysis corresponding to the maximum AUC value when both the sensitivity and specificity are greater than 85%.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events</measure>
    <time_frame>Every 3 months up to 1 year</time_frame>
    <description>Will be graded using Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Early dynamic fluciclovine PET time-activity curve values which distinguish true tumor recurrence from radionecrosis</measure>
    <time_frame>Up to 4 weeks post study registration</time_frame>
    <description>Will be chosen as the threshold with the best cutpoint/threshold during a Receiver Operating Characteristics analysis corresponding to the maximum area under the curve (AUC) value when both the sensitivity and specificity are greater than 85%.</description>
  </other_outcome>
  <other_outcome>
    <measure>Correlation of static fluciclovine PET SUVpeak, SUVmean, TBRmax, TBRmean, and MTV values with progression free survival</measure>
    <time_frame>Up to 1 year after completion of PET/MR imaging</time_frame>
    <description>Differences in progression free survival time between patient groups based on the determined thresholds will be analyzed via Kaplan-Meier methods.</description>
  </other_outcome>
  <other_outcome>
    <measure>Correlation of SUV values with Ki67 staining</measure>
    <time_frame>Up to 4 weeks post study registration</time_frame>
    <description>In patients with true tumor progression, SUV values will be correlated with Ki67 staining on final pathology. Spearman correlation analysis will be performed to determine if a relationship exists between SUV values and Ki67 staining values in patients with tumor progression.</description>
  </other_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Metastatic Intracranial Malignant Neoplasm</condition>
  <condition>Recurrent Intracranial Neoplasm</condition>
  <arm_group>
    <arm_group_label>Diagnostic (18F-fluciclovine, PET/MRI imaging)</arm_group_label>
    <description>Patients receive fluciclovine IV and undergo brain dynamic PET/MRI imaging over 50 minutes.</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Dynamic Contrast-Enhanced Magnetic Resonance Imaging with Positron Emission Tomography</intervention_name>
    <description>Undergo PET-MRI imaging</description>
    <arm_group_label>Diagnostic (18F-fluciclovine, PET/MRI imaging)</arm_group_label>
    <other_name>DCE-MRI with PET</other_name>
    <other_name>DCE-MRI/PET</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Fluciclovine F18</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Diagnostic (18F-fluciclovine, PET/MRI imaging)</arm_group_label>
    <other_name>(18F)Fluciclovine</other_name>
    <other_name>(18F)GE-148</other_name>
    <other_name>18F-Fluciclovine</other_name>
    <other_name>[18F]FACBC</other_name>
    <other_name>Anti-(18f)FABC</other_name>
    <other_name>Anti-1-Amino-3-[18F]Fluorocyclobutane-1-Carboxylic Acid</other_name>
    <other_name>Anti-[18F] FACBC</other_name>
    <other_name>Axumin</other_name>
    <other_name>Fluciclovine (18F)</other_name>
    <other_name>FLUCICLOVINE F-18</other_name>
    <other_name>GE-148 (18F)</other_name>
    <other_name>GE-148 F-18</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with intracranial metastatic disease (brain tumor) that has been treated with&#xD;
        radiation therapy.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Clinical evidence of intracranial metastatic disease which underwent radiation and who&#xD;
             presents with MRI findings suspicious for recurrent disease and/or radionecrosis&#xD;
             (namely the 'index lesion')&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Contraindication to contrast enhanced MRI&#xD;
&#xD;
          -  Females of child-bearing potential who are pregnant or lactating or who are not using&#xD;
             adequate contraception (surgical, hormonal or double barrier, i.e. condom and&#xD;
             diaphragm)&#xD;
&#xD;
          -  Inability to lie still for 50 minutes during fluciclovine PET-MRI imaging&#xD;
&#xD;
          -  Inability or refusal to consent&#xD;
&#xD;
          -  Allergy or anaphylaxis to any of the reagents used in this study&#xD;
&#xD;
          -  Inability or unwillingness to return for required visits and follow-up exams&#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>Daniel Trifiletti</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic in Florida</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32224-9980</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Clinical Trials Referral Office</last_name>
      <phone>855-776-0015</phone>
      <email>mayocliniccancerstudies@mayo.edu</email>
    </contact>
    <investigator>
      <last_name>Daniel Trifiletti, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>June 29, 2020</study_first_submitted>
  <study_first_submitted_qc>July 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 8, 2020</study_first_posted>
  <last_update_submitted>January 5, 2023</last_update_submitted>
  <last_update_submitted_qc>January 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Brain Neoplasms</mesh_term>
    <mesh_term>Radiation Injuries</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04462419
org study id: MC1975
secondary id: NCI-2020-04564
secondary id: MC1975
nct id: NCT04462419
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This phase I trial studies the ability and amount of fluciclovine positron emission
      tomography (PET) imaging needed to recognize tumors that have come back (recurrence) after
      brain injury from radiation therapy (radionecrosis) in patients with intracranial disease
      that has spread to other places in the body (metastatic). F-18 fluciclovine is a radiotracer
      that works by accumulating in tumor cells, making it easier to detect tumors. The results of
      this study may also help investigators understand all the ways that F-18 fluciclovine may
      affect patients.
PRIMARY OBJECTIVE:

      I. To determine the static fluciclovine F18 (fluciclovine) PET imaging tumor-to-background
      ratios (TBRmax; TBRmean) which distinguish true tumor recurrence from radionecrosis in
      patients with intracranial metastatic disease previously treated with radiation therapy, and
      magnetic resonance imaging (MRI) findings suggesting recurrent disease, using histopathology
      as proof of disease.

      SECONDARY OBJECTIVES:

      I. To determine static fluciclovine PET standardized uptake value (SUV)peak, SUVmean values
      and metabolic tumor volumes (MTV) which distinguish true tumor recurrence from radionecrosis
      in patients with MRI findings suggesting recurrent disease, using serial MRI as a surrogate
      marker of disease.

      II. To determine early dynamic fluciclovine PET time activity curve values which distinguish
      true tumor recurrence from radionecrosis in patients with MRI findings suggesting recurrent
      disease, using histopathology or serial MRI as a marker of disease.

      III. To correlate the determined static fluciclovine PET SUVpeak, SUVmean, TBRmax, TBRmean,
      and MTV values with progression free survival.

      IV. In patients with true tumor progression, SUV values will be correlated with Ki67 staining
      on final pathology.

      OUTLINE:

      Patients receive fluciclovine intravenously (IV) and undergo brain dynamic PET/MRI imaging
      over 50 minutes.

      After completion of study, patients are followed up every 3 months for up to 1 year.
observational model: Case-Only
time perspective: Prospective
measure: Tumor-to-background ratios (TBR)max and TBRmean thresholds
time frame: Up to 4 weeks post study registration
description: Will be estimated to delineate tumor progression from radionecrosis for use in future studies. The optimal TBRmax and TBRmean thresholds will be chosen as the threshold with the best cutpoint/threshold during a Receiver Operating Characteristics analysis corresponding to the maximum area under the curve (AUC) value when both the sensitivity and specificity are greater than 85%.
measure: Static values for fluciclovine PET standardized uptake value (SUV)peak that distinguish true tumor recurrence from radionecrosis in patients with MRI findings suggesting recurrent disease
time frame: Up to 4 weeks post study registration
description: Determined using serial MRI as a surrogate marker of disease.The optimal SUVpeak, SUVmean and metabolic tumor volumes (MTV) values will be chosen as the threshold with the best cutpoint/threshold during a Receiver Operating Characteristics analysis corresponding to the maximum AUC value when both the sensitivity and specificity are greater than 85%.
measure: Static values for fluciclovine SUVmean that distinguish true tumor recurrence from radionecrosis in patients with MRI findings suggesting recurrent disease
time frame: Up to 4 weeks post study registration
description: Determined using serial MRI as a surrogate marker of disease. The optimal SUVmean values will be chosen as the threshold with the best cutpoint/threshold during a Receiver Operating Characteristics analysis corresponding to the maximum AUC value when both the sensitivity and specificity are greater than 85%.
measure: Static values for metabolic tumor volumes (MTV) that distinguish true tumor recurrence from radionecrosis in patients with MRI findings suggesting recurrent disease
time frame: Up to 4 weeks post study registration
description: Determined using serial MRI as a surrogate marker of disease. The optimal MTV values will be chosen as the threshold with the best cutpoint/threshold during a Receiver Operating Characteristics analysis corresponding to the maximum AUC value when both the sensitivity and specificity are greater than 85%.
measure: Incidence of adverse events
time frame: Every 3 months up to 1 year
description: Will be graded using Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0.
measure: Early dynamic fluciclovine PET time-activity curve values which distinguish true tumor recurrence from radionecrosis
time frame: Up to 4 weeks post study registration
description: Will be chosen as the threshold with the best cutpoint/threshold during a Receiver Operating Characteristics analysis corresponding to the maximum area under the curve (AUC) value when both the sensitivity and specificity are greater than 85%.
measure: Correlation of static fluciclovine PET SUVpeak, SUVmean, TBRmax, TBRmean, and MTV values with progression free survival
time frame: Up to 1 year after completion of PET/MR imaging
description: Differences in progression free survival time between patient groups based on the determined thresholds will be analyzed via Kaplan-Meier methods.
measure: Correlation of SUV values with Ki67 staining
time frame: Up to 4 weeks post study registration
description: In patients with true tumor progression, SUV values will be correlated with Ki67 staining on final pathology. Spearman correlation analysis will be performed to determine if a relationship exists between SUV values and Ki67 staining values in patients with tumor progression.
arm group label: Diagnostic (18F-fluciclovine, PET/MRI imaging)
description: Patients receive fluciclovine IV and undergo brain dynamic PET/MRI imaging over 50 minutes.
intervention type: Radiation
intervention name: Dynamic Contrast-Enhanced Magnetic Resonance Imaging with Positron Emission Tomography
description: Undergo PET-MRI imaging
arm group label: Diagnostic (18F-fluciclovine, PET/MRI imaging)
other name: DCE-MRI with PET
other name: DCE-MRI/PET
intervention type: Other
intervention name: Fluciclovine F18
description: Given IV
arm group label: Diagnostic (18F-fluciclovine, PET/MRI imaging)
other name: (18F)Fluciclovine
other name: (18F)GE-148
other name: 18F-Fluciclovine
other name: [18F]FACBC
other name: Anti-(18f)FABC
other name: Anti-1-Amino-3-[18F]Fluorocyclobutane-1-Carboxylic Acid
other name: Anti-[18F] FACBC
other name: Axumin
other name: Fluciclovine (18F)
other name: FLUCICLOVINE F-18
other name: GE-148 (18F)
other name: GE-148 F-18
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Daniel Trifiletti
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Brain Neoplasms
mesh term: Radiation Injuries