<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/NCT03762759</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00106863</org_study_id>
    <secondary_id>NCI-2018-02702</secondary_id>
    <secondary_id>RAD4516-18</secondary_id>
    <secondary_id>R01CA226992</secondary_id>
    <secondary_id>P30CA138292</secondary_id>
    <nct_id>NCT03762759</nct_id>
  </id_info>
  <brief_title>Fluciclovine F18 or Ga68-PSMA PET/CT to Enhance Prostate Cancer Outcomes</brief_title>
  <official_title>Advanced PET-CT Directed Post-Prostatectomy Radiotherapy to Enhance Prostate Cancer Outcomes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Emory University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Telix International Pty Ltd</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Emory University</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 a positron emission tomography (PET)/computed tomography&#xD;
      (CT) scan using fluciclovine F18 compared with a PET/CT scan with 68Ga-PSMA works in planning&#xD;
      radiation treatments and enhancing outcomes in patients with prostate adenocarcinoma.&#xD;
      Fluciclovine F18 and 68Ga-PSMA are types of tracers, called radiotracers, that are injected&#xD;
      and can accumulate in tumor cells to develop images of them during a PET/CT scan. It is not&#xD;
      yet known whether giving fluciclovine F18 or 68Ga-PSMA may work better in planning radiation&#xD;
      treatments and enhancing outcomes in patients with prostate adenocarcinoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES&#xD;
&#xD;
      I. Improve the outcomes of post-prostatectomy radiotherapy prostate cancer patients via&#xD;
      selection and treatment optimization with advanced molecular imaging with dose escalation.&#xD;
&#xD;
      II. Establish the role of advanced molecular imaging with fluciclovine F18 (fluciclovine&#xD;
      [18F]) and gallium Ga68-labeled prostate specific membrane antigen PSMA-11 (68Ga-PSMA) PET/CT&#xD;
      in influencing post-prostatectomy radiotherapy decision-making.&#xD;
&#xD;
      III. Establish the role of advanced molecular imaging with fluciclovine 18F or 68Ga-PSMA in&#xD;
      altering radiotherapy treatment volumes.&#xD;
&#xD;
      OUTLINE: Patients are randomized to 1 of 2 arms.&#xD;
&#xD;
      ARM I: Patients receive fluciclovine F18 intravenously (IV) and undergo a PET/CT over&#xD;
      approximately 30 minutes.&#xD;
&#xD;
      ARM II: Patients receive 68Ga-PSMA IV, wait 60 minutes, then undergo a PET/CT over&#xD;
      approximately 30 minutes.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 6 months for up to 5&#xD;
      years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">May 10, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2025</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Disease-free survival</measure>
    <time_frame>Up to 2 years after study start</time_frame>
    <description>A survival analysis will be conducted on disease-free survival (DFS). The survivor functions for DFS will be estimated with Kaplan and Meier method and plotted. The logrank test will be used to test the difference in DFS of (a) both arms in aggregate with the survivor function on our prior R01 trial and (b) between the two study arms.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Decision to offer radiotherapy</measure>
    <time_frame>Up to 5 years after study start</time_frame>
    <description>Decision to offer radiotherapy or not between the initial (pre-fluciclovine F18 or 68Ga-PSMA) and final (post-fluciclovine F18 or 68Ga-PSMA) treatment decisions will be compared using the Clopper-Pearson (exact) binomial test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Decision to treat pelvic nodes</measure>
    <time_frame>Up to 5 years after study start</time_frame>
    <description>Decision to provide treatment on pelvic nodes or not between the initial (pre-fluciclovine F18 or 68Ga-PSMA) and final (post-fluciclovine F18 or 68Ga-PSMA) treatment decisions will be compared using the Clopper-Pearson (exact) binomial test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Decision to boost between the initial and final treatment decisions</measure>
    <time_frame>Up to 5 years after study start</time_frame>
    <description>Decision to boost or not between the initial (pre-fluciclovine F18 or 68Ga-PSMA) and final (post-fluciclovine F18 or 68Ga-PSMA) treatment decisions will be compared using the Clopper-Pearson (exact) binomial test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prostate bed clinical target volume (CTV) and planning target volume (PTV)</measure>
    <time_frame>Up to 5 years after study start</time_frame>
    <description>Paired t-test will be used to compare the target volumes (CTV and PTV) and the planned dose delivered to surrounding bladder, rectum, and penile bulb between the initial (pre-positron emission tomography [PET]) and final (post-PET) radiation treatment plans.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PTV of the rectum (V65, V40)</measure>
    <time_frame>Up to 5 years after study start</time_frame>
    <description>Spearman's correlation coefficient will be used to measure the correlations of the bladder and rectum dosimetric endpoints (V65, V40) with the grades (0, 1, 2, or 3) of acute genitourinary (GU) or gastrointestinal (GI) toxicity. A Wald test will be used to test the significance level of their correlations. A Cox model will be employed to assess the relationship between the time to late GU or GI toxicity (grade ≥ 2) and the bladder and rectum dosimetric endpoints (V65, V40), respectively.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PTV of the bladder (V65, V40)</measure>
    <time_frame>Up to 5 years after study start</time_frame>
    <description>Spearman's correlation coefficient will be used to measure the correlations of the bladder and rectum dosimetric endpoints (V65, V40) with the grades (0, 1, 2, or 3) of acute GU or GI toxicity. A Wald test will be used to test the significance level of their correlations. A Cox model will be employed to assess the relationship between the time to late GU or GI toxicity (grade ≥ 2) and the bladder and rectum dosimetric endpoints (V65, V40), respectively.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">140</enrollment>
  <condition>Prostate Adenocarcinoma</condition>
  <arm_group>
    <arm_group_label>Arm I (fluciclovine F18, PET/CT)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive fluciclovine F18 IV and undergo positron emission tomography (PET)/computed tomography (CT) over 30 minutes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm II (68Ga-PSMA, PET/CT)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients receive gallium Ga68-labeled PSMA-11 IV, wait 60 minutes, then undergo positron emission tomography (PET)/computed tomography (CT) over 30 minutes.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Computed Tomography</intervention_name>
    <description>Undergo PET/CT</description>
    <arm_group_label>Arm I (fluciclovine F18, PET/CT)</arm_group_label>
    <arm_group_label>Arm II (68Ga-PSMA, PET/CT)</arm_group_label>
    <other_name>CT</other_name>
    <other_name>CT scan</other_name>
    <other_name>Computerized axial tomography</other_name>
    <other_name>CAT</other_name>
    <other_name>CAT scan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fluciclovine F18</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (fluciclovine F18, PET/CT)</arm_group_label>
    <other_name>anti-3-[18F]FACBC</other_name>
    <other_name>Anti-1-Amino-3-[18F]Fluorocyclobutane-1-Carboxylic Acid</other_name>
    <other_name>FACBC</other_name>
    <other_name>[18F]FACBC</other_name>
    <other_name>Axumin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Gallium Ga68-labeled PSMA-11</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm II (68Ga-PSMA, PET/CT)</arm_group_label>
    <other_name>68Ga-PSMA</other_name>
    <other_name>68Ga PSMA</other_name>
    <other_name>[68Ga] Prostate-specific Membrane Antigen 11</other_name>
    <other_name>68Ga-DKFZ-PSMA-11</other_name>
    <other_name>68Ga-PSMA-HBED-CC</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Positron Emission Tomography</intervention_name>
    <description>Undergo PET/CT</description>
    <arm_group_label>Arm I (fluciclovine F18, PET/CT)</arm_group_label>
    <arm_group_label>Arm II (68Ga-PSMA, PET/CT)</arm_group_label>
    <other_name>PET</other_name>
    <other_name>PET scan</other_name>
    <other_name>Proton magnetic resonance spectroscopic imaging</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adenocarcinoma of the prostate, post radical-prostatectomy&#xD;
&#xD;
          -  Detectable prostate-specific antigen (PSA)&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG)/Zubrod performance status of 0-2&#xD;
&#xD;
          -  No definitive findings for skeletal metastasis on technetium 99-m methyl diphosphonate&#xD;
             (MDP) or F-18 PET bone scan&#xD;
&#xD;
          -  No definitive findings of systemic (extrapelvic) metastasis on CT and/or magnetic&#xD;
             resonance (MR) scan of abdomen and pelvis&#xD;
&#xD;
          -  Willingness to undergo pelvic radiotherapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Contraindications to radiotherapy (including active inflammatory bowel disease or&#xD;
             prior pelvic radiotherapy)&#xD;
&#xD;
          -  Inability to undergo fluciclovine or Ga-PSMA PET-CT&#xD;
&#xD;
          -  Definitive findings of systemic metastasis on conventional imaging or biopsy&#xD;
&#xD;
          -  Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free&#xD;
             for a minimum of 3 years&#xD;
&#xD;
          -  Severe acute co-morbidity, defined as follows:&#xD;
&#xD;
               -  Unstable angina and/or congestive heart failure requiring hospitalization in the&#xD;
                  last 3 months&#xD;
&#xD;
               -  Transmural myocardial infarction within the last 6 months&#xD;
&#xD;
               -  Acute bacterial or fungal infection requiring intravenous antibiotics at the time&#xD;
                  of registration&#xD;
&#xD;
               -  Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness&#xD;
                  requiring hospitalization or precluding study therapy at the time of registration&#xD;
&#xD;
               -  Acquired immune deficiency syndrome (AIDS) based upon current Center for Disease&#xD;
                  Control (CDC) definition; note, however, that human immunodeficiency virus (HIV)&#xD;
                  testing is not required for entry into this protocol. The need to exclude&#xD;
                  patients with AIDS from this protocol is necessary because the treatments&#xD;
                  involved in this protocol may be significantly immunosuppressive.&#xD;
                  Protocol-specific requirements may also exclude immunocompromised patients&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ashesh Jani, MD, MSEE</last_name>
    <role>Principal Investigator</role>
    <affiliation>Emory University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Grady Health System</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University Hospital/Winship Cancer Institute</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory Saint Joseph's Hospital</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30342</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>November 27, 2018</study_first_submitted>
  <study_first_submitted_qc>November 30, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 4, 2018</study_first_posted>
  <last_update_submitted>May 4, 2023</last_update_submitted>
  <last_update_submitted_qc>May 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Emory University</investigator_affiliation>
    <investigator_full_name>Ashesh B Jani</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenocarcinoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gallium 68 PSMA-11</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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>October 17, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/59/NCT03762759/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03762759
org study id: IRB00106863
secondary id: NCI-2018-02702
secondary id: RAD4516-18
secondary id: R01CA226992
secondary id: P30CA138292
nct id: NCT03762759
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies how well a positron emission tomography (PET)/computed tomography
      (CT) scan using fluciclovine F18 compared with a PET/CT scan with 68Ga-PSMA works in planning
      radiation treatments and enhancing outcomes in patients with prostate adenocarcinoma.
      Fluciclovine F18 and 68Ga-PSMA are types of tracers, called radiotracers, that are injected
      and can accumulate in tumor cells to develop images of them during a PET/CT scan. It is not
      yet known whether giving fluciclovine F18 or 68Ga-PSMA may work better in planning radiation
      treatments and enhancing outcomes in patients with prostate adenocarcinoma.
PRIMARY OBJECTIVES

      I. Improve the outcomes of post-prostatectomy radiotherapy prostate cancer patients via
      selection and treatment optimization with advanced molecular imaging with dose escalation.

      II. Establish the role of advanced molecular imaging with fluciclovine F18 (fluciclovine
      [18F]) and gallium Ga68-labeled prostate specific membrane antigen PSMA-11 (68Ga-PSMA) PET/CT
      in influencing post-prostatectomy radiotherapy decision-making.

      III. Establish the role of advanced molecular imaging with fluciclovine 18F or 68Ga-PSMA in
      altering radiotherapy treatment volumes.

      OUTLINE: Patients are randomized to 1 of 2 arms.

      ARM I: Patients receive fluciclovine F18 intravenously (IV) and undergo a PET/CT over
      approximately 30 minutes.

      ARM II: Patients receive 68Ga-PSMA IV, wait 60 minutes, then undergo a PET/CT over
      approximately 30 minutes.

      After completion of study treatment, patients are followed up every 6 months for up to 5
      years.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Disease-free survival
time frame: Up to 2 years after study start
description: A survival analysis will be conducted on disease-free survival (DFS). The survivor functions for DFS will be estimated with Kaplan and Meier method and plotted. The logrank test will be used to test the difference in DFS of (a) both arms in aggregate with the survivor function on our prior R01 trial and (b) between the two study arms.
measure: Decision to offer radiotherapy
time frame: Up to 5 years after study start
description: Decision to offer radiotherapy or not between the initial (pre-fluciclovine F18 or 68Ga-PSMA) and final (post-fluciclovine F18 or 68Ga-PSMA) treatment decisions will be compared using the Clopper-Pearson (exact) binomial test.
measure: Decision to treat pelvic nodes
time frame: Up to 5 years after study start
description: Decision to provide treatment on pelvic nodes or not between the initial (pre-fluciclovine F18 or 68Ga-PSMA) and final (post-fluciclovine F18 or 68Ga-PSMA) treatment decisions will be compared using the Clopper-Pearson (exact) binomial test.
measure: Decision to boost between the initial and final treatment decisions
time frame: Up to 5 years after study start
description: Decision to boost or not between the initial (pre-fluciclovine F18 or 68Ga-PSMA) and final (post-fluciclovine F18 or 68Ga-PSMA) treatment decisions will be compared using the Clopper-Pearson (exact) binomial test.
measure: Prostate bed clinical target volume (CTV) and planning target volume (PTV)
time frame: Up to 5 years after study start
description: Paired t-test will be used to compare the target volumes (CTV and PTV) and the planned dose delivered to surrounding bladder, rectum, and penile bulb between the initial (pre-positron emission tomography [PET]) and final (post-PET) radiation treatment plans.
measure: PTV of the rectum (V65, V40)
time frame: Up to 5 years after study start
description: Spearman's correlation coefficient will be used to measure the correlations of the bladder and rectum dosimetric endpoints (V65, V40) with the grades (0, 1, 2, or 3) of acute genitourinary (GU) or gastrointestinal (GI) toxicity. A Wald test will be used to test the significance level of their correlations. A Cox model will be employed to assess the relationship between the time to late GU or GI toxicity (grade ≥ 2) and the bladder and rectum dosimetric endpoints (V65, V40), respectively.
measure: PTV of the bladder (V65, V40)
time frame: Up to 5 years after study start
description: Spearman's correlation coefficient will be used to measure the correlations of the bladder and rectum dosimetric endpoints (V65, V40) with the grades (0, 1, 2, or 3) of acute GU or GI toxicity. A Wald test will be used to test the significance level of their correlations. A Cox model will be employed to assess the relationship between the time to late GU or GI toxicity (grade ≥ 2) and the bladder and rectum dosimetric endpoints (V65, V40), respectively.
arm group label: Arm I (fluciclovine F18, PET/CT)
arm group type: Experimental
description: Patients receive fluciclovine F18 IV and undergo positron emission tomography (PET)/computed tomography (CT) over 30 minutes.
arm group label: Arm II (68Ga-PSMA, PET/CT)
arm group type: Active Comparator
description: Patients receive gallium Ga68-labeled PSMA-11 IV, wait 60 minutes, then undergo positron emission tomography (PET)/computed tomography (CT) over 30 minutes.
intervention type: Procedure
intervention name: Computed Tomography
description: Undergo PET/CT
arm group label: Arm I (fluciclovine F18, PET/CT)
arm group label: Arm II (68Ga-PSMA, PET/CT)
other name: CT
other name: CT scan
other name: Computerized axial tomography
other name: CAT
other name: CAT scan
intervention type: Drug
intervention name: Fluciclovine F18
description: Given IV
arm group label: Arm I (fluciclovine F18, PET/CT)
other name: anti-3-[18F]FACBC
other name: Anti-1-Amino-3-[18F]Fluorocyclobutane-1-Carboxylic Acid
other name: FACBC
other name: [18F]FACBC
other name: Axumin
intervention type: Radiation
intervention name: Gallium Ga68-labeled PSMA-11
description: Given IV
arm group label: Arm II (68Ga-PSMA, PET/CT)
other name: 68Ga-PSMA
other name: 68Ga PSMA
other name: [68Ga] Prostate-specific Membrane Antigen 11
other name: 68Ga-DKFZ-PSMA-11
other name: 68Ga-PSMA-HBED-CC
intervention type: Procedure
intervention name: Positron Emission Tomography
description: Undergo PET/CT
arm group label: Arm I (fluciclovine F18, PET/CT)
arm group label: Arm II (68Ga-PSMA, PET/CT)
other name: PET
other name: PET scan
other name: Proton magnetic resonance spectroscopic imaging
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ashesh Jani, MD, MSEE
role: Principal Investigator
affiliation: Emory University
facility: 
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Emory University
investigator full name: Ashesh B Jani
investigator title: Principal Investigator
mesh term: Adenocarcinoma
mesh term: Gallium 68 PSMA-11
sharing ipd: No
provided document: 