<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/NCT04457245</url>
  </required_header>
  <id_info>
    <org_study_id>20-000378</org_study_id>
    <secondary_id>NCI-2020-03445</secondary_id>
    <nct_id>NCT04457245</nct_id>
  </id_info>
  <brief_title>Randomized Trial of PSMA PET Scan Before Definitive Radiation Therapy for Prostate Cancer</brief_title>
  <acronym>PSMA-dRT</acronym>
  <official_title>Phase 3 Randomized Trial Of PSMA PET Prior to Definitive Radiation Therapy for Unfavorable Intermediate-Risk or High-Risk Prostate Cancer [PSMA dRT]</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jonsson Comprehensive Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Progenics Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Jonsson Comprehensive Cancer Center</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This randomized phase III trial studies the success rate of definitive radiation therapy&#xD;
      (dRT) for prostate cancer (PCa) with or without planning based on PSMA PET. PSMA- PET-based&#xD;
      dRT, may improve radiation therapy planning and patient selection for dRT, and potentially&#xD;
      improve its outcome compared to dRT without PSMA PET (standard dRT).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To compare the outcome of patients with unfavorable intermediate (IR) and high-risk (HR)&#xD;
      prostate cancer (PCa) after standard dRT versus prostate-specific membrane antigen (PSMA)&#xD;
      positron emission tomography (PET)-based dRT.&#xD;
&#xD;
      OUTLINE: Patients are randomized to 1 of 2 arms. In both arms, no other primary treatment&#xD;
      should be given before RT.&#xD;
&#xD;
      Arm I: Patients do not undergo PSMA PET for dRT planning. Patients undergo standard of care&#xD;
      dRT at the discretion of the treating radiation oncologist.&#xD;
&#xD;
      Arm II: Patients undergo PSMA PET for dRT planning. Patients then undergo dRT at the&#xD;
      discretion of the treating radiation oncologist, who receives the PSMA PET result and images.&#xD;
&#xD;
      After completion of dRT, clinical follow-up of patients with their treating radiation&#xD;
      oncologist will be obtained for 5 years. The investigators will rely on the medical records&#xD;
      obtained from the treating physicians as the primary source of outcome data.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    accrual&#xD;
  </why_stopped>
  <start_date type="Actual">August 14, 2020</start_date>
  <completion_date type="Actual">January 10, 2023</completion_date>
  <primary_completion_date type="Actual">January 10, 2023</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Success rate of definitive radiation therapy (dRT)</measure>
    <time_frame>From date of randomization to first occurrence of progression, assessed up to 5 years</time_frame>
    <description>Will be measured as progression-free survival after initiation of dRT. Progression is defined as (whichever occurs first): A biochemical recurrence defined as a rise by 2 ng/mL or more above the nadir prostate specific antigen (PSA) (defined as the lowest PSA achieved) after radiotherapy with or without short-term hormonal therapy, appearance of metastasis or loco-regional recurrence (diagnosed by any imaging or biopsy), initiation of any new salvage therapy or death from any cause. Survival curves will be constructed using the Kaplan-Meier method.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Loco-regional progression free survival</measure>
    <time_frame>Up to 5 years after the date of randomization</time_frame>
    <description>Diagnosis of local recurrence or pelvic nodal disease (N1) can be obtained by any imaging or biopsy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Metastasis-free survival after initiation of radiation therapy (RT)</measure>
    <time_frame>Up to 5 years after the date of randomization</time_frame>
    <description>Diagnosis of extra-pelvic metastatic (M1) disease can be obtained by any imaging or biopsy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Up to 5 years after the date of randomization</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in initial treatment intent</measure>
    <time_frame>Baseline up to 5 years after the date of randomization</time_frame>
    <description>Will estimate the proportion of subjects in the prostate-specific membrane antigen (PSMA) group that have a change in the initial treatment intent and compute a 95% confidence interval for that proportion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PSMA positron emission tomography (PET) derived predictors of progression-free survival</measure>
    <time_frame>Up to 5 years after the date of randomization</time_frame>
    <description>Will use Cox-proportional hazards regression to assess PSMA PET predictors of progression-free survival.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PSMA PET derived predictors of overall survival</measure>
    <time_frame>Up to 5 years after the date of randomization</time_frame>
    <description>Will use Cox-proportional hazards regression to assess PSMA PET predictors of overall survival.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">54</enrollment>
  <condition>Stage I Prostate Cancer American Joint Committee on Cancer (AJCC) v8</condition>
  <condition>Stage II Prostate Cancer AJCC v8</condition>
  <condition>Stage IIA Prostate Cancer AJCC v8</condition>
  <condition>Stage IIB Prostate Cancer AJCC v8</condition>
  <condition>Stage IIC Prostate Cancer AJCC v8</condition>
  <condition>Stage III Prostate Cancer AJCC v8</condition>
  <condition>Stage IIIA Prostate Cancer AJCC v8</condition>
  <condition>Stage IIIB Prostate Cancer AJCC v8</condition>
  <condition>Stage IIIC Prostate Cancer AJCC v8</condition>
  <arm_group>
    <arm_group_label>Arm I (dRT)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>150 Patients undergo standard dRT at the discretion of the treating radiation oncologist. Patient does not undergo PSMA PET for RT planning. Any other imaging is allowed, including CT/BS/MR/PET depending on local practice. No other primary treatment can be given before dRT. If a patient assigned to the control arm undergo a PSMA PET scan at another institution he will be discontinued from the study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm II (18F-DCFPyL, PET/CT, dRT)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>162 Patient undergoes PSMA PET with 18F-DCFPyL for dRT planning. Any other imaging is allowed, including CT/BS/MR/PET depending on local practice. Patients then undergo dRT at the discretion of the treating radiation oncologist, who receives PSMA PET results and images. No other primary treatment can be given before RT.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Computed Tomography</intervention_name>
    <description>Undergo whole body PET/CT</description>
    <arm_group_label>Arm II (18F-DCFPyL, PET/CT, dRT)</arm_group_label>
    <other_name>CAT</other_name>
    <other_name>CAT Scan</other_name>
    <other_name>Computerized Axial Tomography</other_name>
    <other_name>Computerized Tomography</other_name>
    <other_name>CT</other_name>
    <other_name>CT Scan</other_name>
    <other_name>tomography</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Fluorine F 18 DCFPyL</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm II (18F-DCFPyL, PET/CT, dRT)</arm_group_label>
    <other_name>18F-DCFPyL</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Positron Emission Tomography</intervention_name>
    <description>Undergo whole body PET/CT</description>
    <arm_group_label>Arm II (18F-DCFPyL, PET/CT, dRT)</arm_group_label>
    <other_name>Medical Imaging, Positron Emission Tomography</other_name>
    <other_name>PET</other_name>
    <other_name>PET Scan</other_name>
    <other_name>Positron Emission Tomography Scan</other_name>
    <other_name>Positron-Emission Tomography</other_name>
    <other_name>proton magnetic resonance spectroscopic imaging</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Radiation Therapy</intervention_name>
    <description>Undergo standard of care definitive radiation therapy</description>
    <arm_group_label>Arm I (dRT)</arm_group_label>
    <arm_group_label>Arm II (18F-DCFPyL, PET/CT, dRT)</arm_group_label>
    <other_name>Cancer Radiotherapy</other_name>
    <other_name>Irradiate</other_name>
    <other_name>Irradiated</other_name>
    <other_name>Irradiation</other_name>
    <other_name>Radiation</other_name>
    <other_name>Radiation Therapy, NOS</other_name>
    <other_name>Radiotherapeutics</other_name>
    <other_name>Radiotherapy</other_name>
    <other_name>RT</other_name>
    <other_name>Therapy, Radiation</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult male 18 years or older&#xD;
&#xD;
          -  Histopathologically-proven PCa&#xD;
&#xD;
          -  Unfavorable IR to HR disease:&#xD;
&#xD;
               -  Prostate specific antigen (PSA) &gt;= 10 ng/mL&#xD;
&#xD;
               -  Or cT-stage &gt;= 2b&#xD;
&#xD;
               -  Or Gleason grade 3 (4+3=7) or higher&#xD;
&#xD;
               -  Or Gleason grade 2 (3+4=7) AND &gt;= 50% positive biopsy cores&#xD;
&#xD;
               -  Or Decipher Score &gt;= 0.45&#xD;
&#xD;
          -  Treating radiation oncologist intends to incorporate PSMA PET findings into the&#xD;
             radiotherapy plan, if patient undergoes PSMA PET (intervention arm 2)&#xD;
&#xD;
          -  Provision of signed and dated informed consent form&#xD;
&#xD;
          -  Stated willingness to comply with all study procedures and availability for the&#xD;
             duration of the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Less than 18 years old at the time of investigational product administration&#xD;
&#xD;
          -  Extra-pelvic metastasis (M1 disease) on any imaging or biopsy done before&#xD;
             randomization&#xD;
&#xD;
          -  Prior PSMA PET&#xD;
&#xD;
          -  Prior pelvic RT&#xD;
&#xD;
          -  Contraindications to radiotherapy (including active inflammatory bowel disease)&#xD;
&#xD;
          -  Concurrent or prior surgery or systemic therapy for PCa at the time of randomization&#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>Jeremie Calais</last_name>
    <role>Principal Investigator</role>
    <affiliation>UCLA / Jonsson Comprehensive Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UCLA / Jonsson Comprehensive Cancer Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>June 30, 2020</study_first_submitted>
  <study_first_submitted_qc>June 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>January 12, 2023</last_update_submitted>
  <last_update_submitted_qc>January 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 17, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PSMA</keyword>
  <keyword>PET/CT</keyword>
  <keyword>randomized trial</keyword>
  <keyword>definitive Radiation Therapy</keyword>
  <keyword>prostate cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fluorides</mesh_term>
  </intervention_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/NCT04457245
org study id: 20-000378
secondary id: NCI-2020-03445
nct id: NCT04457245
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This randomized phase III trial studies the success rate of definitive radiation therapy
      (dRT) for prostate cancer (PCa) with or without planning based on PSMA PET. PSMA- PET-based
      dRT, may improve radiation therapy planning and patient selection for dRT, and potentially
      improve its outcome compared to dRT without PSMA PET (standard dRT).
PRIMARY OBJECTIVE:

      I. To compare the outcome of patients with unfavorable intermediate (IR) and high-risk (HR)
      prostate cancer (PCa) after standard dRT versus prostate-specific membrane antigen (PSMA)
      positron emission tomography (PET)-based dRT.

      OUTLINE: Patients are randomized to 1 of 2 arms. In both arms, no other primary treatment
      should be given before RT.

      Arm I: Patients do not undergo PSMA PET for dRT planning. Patients undergo standard of care
      dRT at the discretion of the treating radiation oncologist.

      Arm II: Patients undergo PSMA PET for dRT planning. Patients then undergo dRT at the
      discretion of the treating radiation oncologist, who receives the PSMA PET result and images.

      After completion of dRT, clinical follow-up of patients with their treating radiation
      oncologist will be obtained for 5 years. The investigators will rely on the medical records
      obtained from the treating physicians as the primary source of outcome data.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Success rate of definitive radiation therapy (dRT)
time frame: From date of randomization to first occurrence of progression, assessed up to 5 years
description: Will be measured as progression-free survival after initiation of dRT. Progression is defined as (whichever occurs first): A biochemical recurrence defined as a rise by 2 ng/mL or more above the nadir prostate specific antigen (PSA) (defined as the lowest PSA achieved) after radiotherapy with or without short-term hormonal therapy, appearance of metastasis or loco-regional recurrence (diagnosed by any imaging or biopsy), initiation of any new salvage therapy or death from any cause. Survival curves will be constructed using the Kaplan-Meier method.
measure: Loco-regional progression free survival
time frame: Up to 5 years after the date of randomization
description: Diagnosis of local recurrence or pelvic nodal disease (N1) can be obtained by any imaging or biopsy.
measure: Metastasis-free survival after initiation of radiation therapy (RT)
time frame: Up to 5 years after the date of randomization
description: Diagnosis of extra-pelvic metastatic (M1) disease can be obtained by any imaging or biopsy.
measure: Overall survival
time frame: Up to 5 years after the date of randomization
measure: Change in initial treatment intent
time frame: Baseline up to 5 years after the date of randomization
description: Will estimate the proportion of subjects in the prostate-specific membrane antigen (PSMA) group that have a change in the initial treatment intent and compute a 95% confidence interval for that proportion.
measure: PSMA positron emission tomography (PET) derived predictors of progression-free survival
time frame: Up to 5 years after the date of randomization
description: Will use Cox-proportional hazards regression to assess PSMA PET predictors of progression-free survival.
measure: PSMA PET derived predictors of overall survival
time frame: Up to 5 years after the date of randomization
description: Will use Cox-proportional hazards regression to assess PSMA PET predictors of overall survival.
arm group label: Arm I (dRT)
arm group type: Active Comparator
description: 150 Patients undergo standard dRT at the discretion of the treating radiation oncologist. Patient does not undergo PSMA PET for RT planning. Any other imaging is allowed, including CT/BS/MR/PET depending on local practice. No other primary treatment can be given before dRT. If a patient assigned to the control arm undergo a PSMA PET scan at another institution he will be discontinued from the study.
arm group label: Arm II (18F-DCFPyL, PET/CT, dRT)
arm group type: Experimental
description: 162 Patient undergoes PSMA PET with 18F-DCFPyL for dRT planning. Any other imaging is allowed, including CT/BS/MR/PET depending on local practice. Patients then undergo dRT at the discretion of the treating radiation oncologist, who receives PSMA PET results and images. No other primary treatment can be given before RT.
intervention type: Procedure
intervention name: Computed Tomography
description: Undergo whole body PET/CT
arm group label: Arm II (18F-DCFPyL, PET/CT, dRT)
other name: CAT
other name: CAT Scan
other name: Computerized Axial Tomography
other name: Computerized Tomography
other name: CT
other name: CT Scan
other name: tomography
intervention type: Other
intervention name: Fluorine F 18 DCFPyL
description: Given IV
arm group label: Arm II (18F-DCFPyL, PET/CT, dRT)
other name: 18F-DCFPyL
intervention type: Procedure
intervention name: Positron Emission Tomography
description: Undergo whole body PET/CT
arm group label: Arm II (18F-DCFPyL, PET/CT, dRT)
other name: Medical Imaging, Positron Emission Tomography
other name: PET
other name: PET Scan
other name: Positron Emission Tomography Scan
other name: Positron-Emission Tomography
other name: proton magnetic resonance spectroscopic imaging
intervention type: Radiation
intervention name: Radiation Therapy
description: Undergo standard of care definitive radiation therapy
arm group label: Arm I (dRT)
arm group label: Arm II (18F-DCFPyL, PET/CT, dRT)
other name: Cancer Radiotherapy
other name: Irradiate
other name: Irradiated
other name: Irradiation
other name: Radiation
other name: Radiation Therapy, NOS
other name: Radiotherapeutics
other name: Radiotherapy
other name: RT
other name: Therapy, Radiation
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jeremie Calais
role: Principal Investigator
affiliation: UCLA / Jonsson Comprehensive Cancer Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: Fluorides