<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/NCT03253744</url>
  </required_header>
  <id_info>
    <org_study_id>170153</org_study_id>
    <secondary_id>17-C-0153</secondary_id>
    <nct_id>NCT03253744</nct_id>
  </id_info>
  <brief_title>Prostate SBRT for Locally Recurrent Prostate Cancer After Prior Radiotherapy</brief_title>
  <official_title>Phase I Trial of Image Guided Focally Dose Escalated Prostate SBRT for Locally Recurrent Prostate Cancer After Prior Radiotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      Prostate cancer is the second leading cause of cancer death in U.S. men. Radiation is an&#xD;
      effective treatment for most patients with localized prostate cancer, but sometimes the tumor&#xD;
      returns. Researchers want to see if a highly focused type of radiation can help. It is given&#xD;
      in only 5 treatments. It is called stereotactic body radiation therapy (SBRT).&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To study the maximum tolerated dose and side effects of stereotactic body radiation therapy&#xD;
      in people with a local recurrence of prostate cancer after radiation.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      Men at least 18 years old who have recurrent prostate cancer after radiation therapy and no&#xD;
      evidence of distant metastatic disease&#xD;
&#xD;
      Design:&#xD;
&#xD;
      Participants will be screened with blood tests, physical exam, and medical history. They may&#xD;
      also have:&#xD;
&#xD;
      Magnetic resonance imaging (MRI) scan of the prostate..&#xD;
&#xD;
      PET/CT scan. Participants will get an injection of 18F-DCFPyL for the PET scan. They will lie&#xD;
      very still on their back on the scanner table.&#xD;
&#xD;
      Small samples of prostate tumor tissue will be taken by a needle through the skin or rectum&#xD;
      to see if the cancer is in the prostate. Small metal seeds will be placed into the prostate&#xD;
      at the same time to help guide the radiation.&#xD;
&#xD;
      About 2 weeks later, participants will have a radiation treatment planning CT scan.&#xD;
&#xD;
      Participants will answer questions about their urine function, bowel function, erectile&#xD;
      function, and mood.&#xD;
&#xD;
      Participants will receive SBRT. They will have 5 radiation treatments over 2 weeks.&#xD;
&#xD;
      Participants will have follow-up visits. They will have a physical exam, blood tests, and&#xD;
      questionnaires.&#xD;
&#xD;
      Six months after ending SBRT, the 18F-DCFPyL PET/CT will be repeated.&#xD;
&#xD;
      Participantes will continue to have routine visits until two years after treatment is&#xD;
      completed....&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background:&#xD;
&#xD;
        -  Prostate cancer that recurs after prior radiation treatment can be challenging to cure&#xD;
           due to the side effects of available treatments such as surgery and cryoablation.&#xD;
&#xD;
        -  Re-irradiation with brachytherapy or stereotactic approaches has shown excellent rates&#xD;
           of prostate cancer disease control with tolerable side effects.&#xD;
&#xD;
        -  Using image guidance to allow highly conformal focal re-irradiation may potentially&#xD;
           increase the efficacy of re-irradiation.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      -Define the maximum tolerated dose (MTD) of image guided, focally dose escalated prostate&#xD;
      radiation with stereotactic body radiation therapy (SBRT) in patients with a local recurrence&#xD;
      of prostate cancer after prior radiotherapy.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
        -  Histological confirmation of recurrent prostate cancer after prior irradiation (external&#xD;
           beam or brachytherapy)&#xD;
&#xD;
        -  No evidence of distant metastases of prostate cancer&#xD;
&#xD;
        -  No prior prostatectomy&#xD;
&#xD;
        -  Subject is greater than or equal to18 years old&#xD;
&#xD;
        -  ECOG performance status less than or equal to 2 (Karnofsky greater than or equal to&#xD;
           60%).&#xD;
&#xD;
      Design:&#xD;
&#xD;
        -  This is a Phase I trial of focal dose escalation with SBRT using image and pathologic&#xD;
           guidance.&#xD;
&#xD;
        -  Areas in the prostate shown to have tumor on biopsy or with advanced imaging studies&#xD;
           will be treated with highly conformal SBRT over a period of two to three weeks.&#xD;
           Treatment will be guided and gated by fiducials implanted in the prostate.&#xD;
&#xD;
        -  Patients will be treated to escalating doses based on tolerability of the treatment.&#xD;
&#xD;
        -  Quality of life and functional outcomes such as urine, bowel, and erectile function will&#xD;
           be assessed with questionnaires.&#xD;
&#xD;
        -  Up to 52 patients will be enrolled.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 5, 2018</start_date>
  <completion_date type="Anticipated">February 16, 2025</completion_date>
  <primary_completion_date type="Actual">May 3, 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum tolerated dose</measure>
    <time_frame>3 weeks post-treatment</time_frame>
    <description>Define the MTD of image-guided, focally dose escalated prostate SBRT in patients with a local recurrence of prostate cancer after prior radiotherapy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Sensitivity and specifity of 18F-DCFPyl imaging as compared to biopsy in detecting locally recurrent prostate cancer</measure>
    <time_frame>6 months after radiation</time_frame>
    <description>Evaluate 18F-DCFPyL imaging as a method to detect locally recurrent prostate cancer after radiation. The sensitivity and specificity of DCF-PyL for detecting locally recurrent prostate cancer (at baseline) will be reported using biopsy as the gold standard.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes of quality of life scores during and after treatment</measure>
    <time_frame>2 years after treatment</time_frame>
    <description>Describe the effects of focally dose escalated prostate SBRT on patient reported outcomes (SHIM, AUA Symptom Index, EPIC-26) in patients previously treated with radiotherapy. The quality of life scores will be summarized at baseline and for each visit. Linear mixed effects model will be used to model quality of life scores at baseline and during and after treatment in which random intercept and random slope are used to account for patient-specific trajectory of quality of life scores. Changes of quality of life scores during and after treatment will be calculated from the estimated linear mixed effect model.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>biochemical progression free survival</measure>
    <time_frame>1 and 2 years after treamtnet</time_frame>
    <description>Describe the rate of PSA control (bPFS, PSA &lt; 2 ng/dL above post SBRT nadir) at 1 and 2 years after treatment with focally dose escalated SBRT for locally recurrent prostate cancer after irradiation: bPFS will be estimated by the Kaplan-Meier survival analysis and effects of clinical variables on bPFS will be assessed by the Cox proportional hazards model.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of Dose limiting toxicities</measure>
    <time_frame>3 weeks after end of treatment</time_frame>
    <description>Define the dose-limiting toxicities and toxicity profile of image-guided, focally dose escalated prostate SBRT in patients previously treated with radiotherapy: DLTs will be reported descriptively.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">13</enrollment>
  <condition>Prostate Cancer</condition>
  <condition>Prosatatic Neoplasm</condition>
  <arm_group>
    <arm_group_label>1/Tumor Irradiation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SBRT will be delivered to areas of recurrent prostate cancer identified on imaging and biopsy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>2/Prostate and Tumor Irradiation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SBRT will be delivered to areas of recurrent prostate cancer identified on imaging and biopsy; and a reduced dose will be delivered to the entire prostate</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>18F-DCFPyL</intervention_name>
    <description>Subjects will receive 18F-DCFPyL at baseline and 6 months after radiation. The maximum amount of injected active drug will be less than 4.02 micrograms. The target administered activity will be 6-6.5 mCi.</description>
    <arm_group_label>1/Tumor Irradiation</arm_group_label>
    <arm_group_label>2/Prostate and Tumor Irradiation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Tumor Irradiation</intervention_name>
    <description>SBRT will be delivered to areas of recurrent prostate cancer identified on imaging and biopsy</description>
    <arm_group_label>1/Tumor Irradiation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Prostate + tumor irradiation</intervention_name>
    <description>SBRT will be delivered to areas of recurrent prostate cancer identified on imaging and biopsy; and a reduced dose will be delivered to the entire prostate</description>
    <arm_group_label>2/Prostate and Tumor Irradiation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
          -  Patients must have histologically confirmed locally recurrent adenocarcinoma of the&#xD;
             prostate after prior radiation (EBRT or brachytherapy).&#xD;
&#xD;
          -  PSA failure after definitive radiation as defined by the Phoenix criteria (PSA&#xD;
             elevation at least 2 ng/dL above post-radiotherapy nadir)&#xD;
&#xD;
          -  Age greater than or equal to 18 years.&#xD;
&#xD;
          -  ECOG performance status less than or equal to 2 (Karnofsky greater than or equal to&#xD;
             60%).&#xD;
&#xD;
          -  Ability of subject to understand and the willingness to sign a written informed&#xD;
             consent document.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
          -  Patients who are receiving any other investigational agents.&#xD;
&#xD;
          -  PSA greater than or equal to 20 ng/dL if no prior DCFPyL scan obtained (If PSA &gt; 20&#xD;
             and DCFPyL obtained within 3 months prior to enrollment shows no evidence of&#xD;
             metastatic disease, subjects may be included in the study)&#xD;
&#xD;
          -  Biochemical recurrence within one year of completion of radiotherapy&#xD;
&#xD;
          -  Need for chronic anticoagulation therapy (chronic low dose aspirin is not an&#xD;
             exclusion)&#xD;
&#xD;
          -  Pre-existing and ongoing radiation-related grade 3 bowel or bladder toxicity&#xD;
&#xD;
          -  Inflammatory bowel disease&#xD;
&#xD;
          -  Active Lupus or Active scleroderma&#xD;
&#xD;
          -  Patients with distant metastatic disease (prostate adjacent adenopathy is not an&#xD;
             exclusion)&#xD;
&#xD;
          -  Prior prostatectomy&#xD;
&#xD;
          -  Subjects with any coexisting medical or psychiatric condition that is likely to&#xD;
             interfere with study procedures and/or results.&#xD;
&#xD;
          -  Subjects with severe claustrophobia that is unresponsive to oral anxiolytics&#xD;
&#xD;
          -  Other medical conditions deemed by the Principal Investigator (or associates) to make&#xD;
             the subject unsafe or ineligible for protocol procedures&#xD;
&#xD;
          -  Subjects weighing &gt; 350 lbs. (weight limit for scanner table), or unable to fit within&#xD;
             the imaging gantry&#xD;
&#xD;
          -  Serum creatinine &gt; 2 times the upper limit of normal&#xD;
&#xD;
          -  Total bilirubin &gt; 2 times the upper limit of normal OR in patients with Gilbert s&#xD;
             syndrome, a total bilirubin &gt; 3.0.&#xD;
&#xD;
          -  Liver transaminases (ALT, AST) greater than 3 times the upper limit of normal&#xD;
&#xD;
          -  Patients with positive Human Immunodeficiency Virus (HIV) status and currently&#xD;
             requiring treatment with agents known to sensitize to irradiation, such as protease&#xD;
             inhibitors.&#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>Deborah E Citrin, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Cancer Institute (NCI)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2017-C-0153.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <verification_date>August 9, 2023</verification_date>
  <study_first_submitted>August 17, 2017</study_first_submitted>
  <study_first_submitted_qc>August 17, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 18, 2017</study_first_posted>
  <last_update_submitted>August 10, 2023</last_update_submitted>
  <last_update_submitted_qc>August 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Image Guidance</keyword>
  <keyword>Dose Escalation</keyword>
  <keyword>Radiotherapy</keyword>
  <keyword>Re-irradiation</keyword>
  <keyword>Quality of Life</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>.All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.</ipd_time_frame>
    <ipd_access_criteria>Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. Genomic data are made available via dbGaP through requests to the data custodians.</ipd_access_criteria>
  </patient_data>
  <!-- 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/NCT03253744
org study id: 170153
secondary id: 17-C-0153
nct id: NCT03253744
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
Background:

      Prostate cancer is the second leading cause of cancer death in U.S. men. Radiation is an
      effective treatment for most patients with localized prostate cancer, but sometimes the tumor
      returns. Researchers want to see if a highly focused type of radiation can help. It is given
      in only 5 treatments. It is called stereotactic body radiation therapy (SBRT).

      Objective:

      To study the maximum tolerated dose and side effects of stereotactic body radiation therapy
      in people with a local recurrence of prostate cancer after radiation.

      Eligibility:

      Men at least 18 years old who have recurrent prostate cancer after radiation therapy and no
      evidence of distant metastatic disease

      Design:

      Participants will be screened with blood tests, physical exam, and medical history. They may
      also have:

      Magnetic resonance imaging (MRI) scan of the prostate..

      PET/CT scan. Participants will get an injection of 18F-DCFPyL for the PET scan. They will lie
      very still on their back on the scanner table.

      Small samples of prostate tumor tissue will be taken by a needle through the skin or rectum
      to see if the cancer is in the prostate. Small metal seeds will be placed into the prostate
      at the same time to help guide the radiation.

      About 2 weeks later, participants will have a radiation treatment planning CT scan.

      Participants will answer questions about their urine function, bowel function, erectile
      function, and mood.

      Participants will receive SBRT. They will have 5 radiation treatments over 2 weeks.

      Participants will have follow-up visits. They will have a physical exam, blood tests, and
      questionnaires.

      Six months after ending SBRT, the 18F-DCFPyL PET/CT will be repeated.

      Participantes will continue to have routine visits until two years after treatment is
      completed....
Background:

        -  Prostate cancer that recurs after prior radiation treatment can be challenging to cure
           due to the side effects of available treatments such as surgery and cryoablation.

        -  Re-irradiation with brachytherapy or stereotactic approaches has shown excellent rates
           of prostate cancer disease control with tolerable side effects.

        -  Using image guidance to allow highly conformal focal re-irradiation may potentially
           increase the efficacy of re-irradiation.

      Objectives:

      -Define the maximum tolerated dose (MTD) of image guided, focally dose escalated prostate
      radiation with stereotactic body radiation therapy (SBRT) in patients with a local recurrence
      of prostate cancer after prior radiotherapy.

      Eligibility:

        -  Histological confirmation of recurrent prostate cancer after prior irradiation (external
           beam or brachytherapy)

        -  No evidence of distant metastases of prostate cancer

        -  No prior prostatectomy

        -  Subject is greater than or equal to18 years old

        -  ECOG performance status less than or equal to 2 (Karnofsky greater than or equal to
           60%).

      Design:

        -  This is a Phase I trial of focal dose escalation with SBRT using image and pathologic
           guidance.

        -  Areas in the prostate shown to have tumor on biopsy or with advanced imaging studies
           will be treated with highly conformal SBRT over a period of two to three weeks.
           Treatment will be guided and gated by fiducials implanted in the prostate.

        -  Patients will be treated to escalating doses based on tolerability of the treatment.

        -  Quality of life and functional outcomes such as urine, bowel, and erectile function will
           be assessed with questionnaires.

        -  Up to 52 patients will be enrolled.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerated dose
time frame: 3 weeks post-treatment
description: Define the MTD of image-guided, focally dose escalated prostate SBRT in patients with a local recurrence of prostate cancer after prior radiotherapy.
measure: Sensitivity and specifity of 18F-DCFPyl imaging as compared to biopsy in detecting locally recurrent prostate cancer
time frame: 6 months after radiation
description: Evaluate 18F-DCFPyL imaging as a method to detect locally recurrent prostate cancer after radiation. The sensitivity and specificity of DCF-PyL for detecting locally recurrent prostate cancer (at baseline) will be reported using biopsy as the gold standard.
measure: Changes of quality of life scores during and after treatment
time frame: 2 years after treatment
description: Describe the effects of focally dose escalated prostate SBRT on patient reported outcomes (SHIM, AUA Symptom Index, EPIC-26) in patients previously treated with radiotherapy. The quality of life scores will be summarized at baseline and for each visit. Linear mixed effects model will be used to model quality of life scores at baseline and during and after treatment in which random intercept and random slope are used to account for patient-specific trajectory of quality of life scores. Changes of quality of life scores during and after treatment will be calculated from the estimated linear mixed effect model.
measure: biochemical progression free survival
time frame: 1 and 2 years after treamtnet
description: Describe the rate of PSA control (bPFS, PSA < 2 ng/dL above post SBRT nadir) at 1 and 2 years after treatment with focally dose escalated SBRT for locally recurrent prostate cancer after irradiation: bPFS will be estimated by the Kaplan-Meier survival analysis and effects of clinical variables on bPFS will be assessed by the Cox proportional hazards model.
measure: Assessment of Dose limiting toxicities
time frame: 3 weeks after end of treatment
description: Define the dose-limiting toxicities and toxicity profile of image-guided, focally dose escalated prostate SBRT in patients previously treated with radiotherapy: DLTs will be reported descriptively.
arm group label: 1/Tumor Irradiation
arm group type: Experimental
description: SBRT will be delivered to areas of recurrent prostate cancer identified on imaging and biopsy
arm group label: 2/Prostate and Tumor Irradiation
arm group type: Experimental
description: SBRT will be delivered to areas of recurrent prostate cancer identified on imaging and biopsy; and a reduced dose will be delivered to the entire prostate
intervention type: Drug
intervention name: 18F-DCFPyL
description: Subjects will receive 18F-DCFPyL at baseline and 6 months after radiation. The maximum amount of injected active drug will be less than 4.02 micrograms. The target administered activity will be 6-6.5 mCi.
arm group label: 1/Tumor Irradiation
arm group label: 2/Prostate and Tumor Irradiation
intervention type: Radiation
intervention name: Tumor Irradiation
description: SBRT will be delivered to areas of recurrent prostate cancer identified on imaging and biopsy
arm group label: 1/Tumor Irradiation
intervention type: Radiation
intervention name: Prostate + tumor irradiation
description: SBRT will be delivered to areas of recurrent prostate cancer identified on imaging and biopsy; and a reduced dose will be delivered to the entire prostate
arm group label: 2/Prostate and Tumor Irradiation
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Deborah E Citrin, M.D.
role: Principal Investigator
affiliation: National Cancer Institute (NCI)
facility: 
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2017-C-0153.html
description: NIH Clinical Center Detailed Web Page
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
sharing ipd: Yes
ipd description: .All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
ipd access criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. Genomic data are made available via dbGaP through requests to the data custodians.