<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/NCT04402151</url>
  </required_header>
  <id_info>
    <org_study_id>19-10020928</org_study_id>
    <secondary_id>R01CA249615</secondary_id>
    <nct_id>NCT04402151</nct_id>
  </id_info>
  <brief_title>Study of PSMA PET/MR Guided Stereotactic Body Radiation Therapy With Simultaneous Integrated Boost (SBRT-SIB) for High-Intermediate and High Risk Prostate Cancer</brief_title>
  <acronym>PSMA SBRT-SIB</acronym>
  <official_title>Single-Arm Phase II Study of PSMA PET/MR Guided Stereotactic Body Radiation Therapy With Simultaneous Integrated Boost (SBRT-SIB) for High-Intermediate and High Risk Prostate Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Weill Medical College of Cornell University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Weill Medical College of Cornell University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a single-arm Phase II clinical trial assessing the clinical efficacy of prostate&#xD;
      specific membrane antigen (PSMA) PET/MR guided MR-LINAC based SBRT-SIB with planned accrual&#xD;
      of 50 patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Localized prostate cancer can be treated in 5 sessions using a precise, targeted form of&#xD;
      radiation known as stereotactic body radiation therapy (SBRT), with low toxicity. Despite&#xD;
      these advances, overall outcomes for aggressive (high risk) prostate cancer remain poor, with&#xD;
      10-year recurrence-free survival of approximately 65% regardless of treatment modality.&#xD;
      Recurrences are typically distant and carry poor prognosis, with 5 year survival of 25%. The&#xD;
      investigators propose to utilize the latest advances in cancer imaging (PSMA Positron&#xD;
      Emission Tomography (PET)/Magnetic Resonance Imaging (MR)) and radiation delivery (MR-guided&#xD;
      radiation therapy with real-time adaptive planning), to deliver a personalized radiation&#xD;
      treatment that targets the areas of greatest risk of recurrence in the prostate with improved&#xD;
      precision, and as a result improve clinical outcomes for individuals with high risk prostate&#xD;
      cancer. PSMA PET/MR is a novel imaging modality, not yet widely available, that augments the&#xD;
      tissue detail provided by MR. The combination of PSMA PET with MR results in improved&#xD;
      delineation of intraprostatic nodules and higher diagnostic accuracy for detection of&#xD;
      metastatic disease compared to conventional imaging. PSMA PET/MR imaging data is readily&#xD;
      transferable to a MR-based linear accelerator (MR-LINAC), a novel, innovative platform that&#xD;
      allows direct visualization of the tumor during treatment, and permits real-time&#xD;
      individualized correction for motion with online adaptive radiation planning.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 30, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical efficacy of prostate-specific membrane antigen (PSMA) Positron Emission Tomography (PET)/Magnetic Resonance(MR), MR-Linear Accelerator (LINAC) will be assessed by evaluating recurrence free survival</measure>
    <time_frame>24 months</time_frame>
    <description>Evaluate the clinical efficacy of PSMA PET/MR guided, MR-LINAC-based SBRT- SIB in high-intermediate and high risk prostate cancer, as evaluated by the 2-year recurrence-free survival rate</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Performance of PSMA PET/MR to MR alone at staging prostate cancer</measure>
    <time_frame>Baseline</time_frame>
    <description>Detection of metastatic disease on each scan will be recorded, with pathologic confirmation obtained. Detection of intraprostatic nodules will be recorded with pathologic confirmation obtained.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Performance of PSMA PET/MR to MR alone for identification of dominant intraprostatic nodules during radiation planning</measure>
    <time_frame>Baseline</time_frame>
    <description>The Dominant Intraprostatic Nodules (DIN) will be defined with radiologist assistance on MR alone, and subsequently PSMA PET/MR. The incidence of alterations in target will be recorded.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare imaging biomarkers of interest on MR and PSMA PET/MR as predictors of treatment response, versus biopsy of treatment response and PSA</measure>
    <time_frame>Baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare imaging biomarkers of interest on MR and PSMA PET/MR as predictors of treatment response, versus biopsy of treatment response and PSA</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Quality of life questionnaires (EPIC-26) will be assessed.</measure>
    <time_frame>Baseline, 1month, 6months, 12 months, 18 months and 24 months.</time_frame>
    <description>Expanded Prostate Cancer Index Composite (EPIC) short form questionnaire. The Expanded Prostate Cancer Index Composite (EPIC) is a comprehensive instrument designed to evaluate patient function and bother after prostate cancer treatment. Scores range from 0 to 100, lower scores indicate worse outcomes and higher EPIC scores represent better outcomes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in The American Urological Association (AUA) symptom score</measure>
    <time_frame>Baseline, 1month, 6months, 12 months, 18 months and 24 months.</time_frame>
    <description>The American Urological Association (AUA) has created this symptom index for understanding the severity of enlarged prostate symptoms. Scores ranging from 0-7 are considered to be mild symptoms, 8-19 are moderate and 20 - 35 are severe symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Number of Subjects with Adverse events</measure>
    <time_frame>Baseline, 1month, 6months, 12 months and 24 months.</time_frame>
    <description>Adverse events will be collected from patients based on CTCAE version 5.0.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The change in radiation doses received by the surrounding normal structures/PTV for each initial and adapted plan will be analyzed with a signed-rank Wilcoxon test (non-parametric test for paired comparisons).</measure>
    <time_frame>Baseline, 1month</time_frame>
    <description>PTV is the planning target volume</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare the changes in the Microbiome during SBRT-SIB</measure>
    <time_frame>Baseline</time_frame>
    <description>Gut microbiome samples will be obtained for 16S RNA analyses</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare the changes in the Microbiome during SBRT-SIB</measure>
    <time_frame>approx. 3 weeks</time_frame>
    <description>Gut microbiome samples will be obtained for 16S RNA analyses</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare the changes in the Microbiome during SBRT-SIB</measure>
    <time_frame>12 months</time_frame>
    <description>Gut microbiome samples will be obtained for 16S RNA analyses</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare the immunological changes during SBRT-SIB</measure>
    <time_frame>Baseline</time_frame>
    <description>serum samples will be obtained for immune correlate analyses</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare the immunological changes during SBRT-SIB</measure>
    <time_frame>approx. 3 weeks</time_frame>
    <description>serum samples will be obtained for immune correlate analyses</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare the immunological changes during SBRT-SIB</measure>
    <time_frame>12 months</time_frame>
    <description>serum samples will be obtained for immune correlate analyses</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Single Arm</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patients enrolling on the protocol will undergo prostate-specific membrane antigen (PSMA) Positron Emission Tomography (PET)/Magnetic Resonance(MR) prior to start of the radiation treatment planning process. PSMA tracer is administered by IV injection and PET images are acquired.&#xD;
Any patients found to have possible metastatic disease will undergo a standard of care confirmatory biopsy (if feasible) and receive treatment appropriate for their stage.&#xD;
The PSMA PET/MR scan will be performed prior to initiation of androgen deprivation therapy (ADT).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PSMA PET/MR - Gallium-68 labeled PSMA-HBED-CC</intervention_name>
    <description>Patients enrolling on the protocol will undergo prostate-specific membrane antigen (PSMA) Positron Emission Tomography (PET)/Magnetic Resonance(MR) prior to start of the radiation treatment planning process. PSMA tracer is administered by IV injection and PET images are acquired.&#xD;
Any patients found to have possible metastatic disease will undergo a standard of care confirmatory biopsy (if feasible) and receive treatment appropriate for their stage.&#xD;
The PSMA PET/MR scan will be performed prior to initiation of androgen deprivation therapy (ADT).</description>
    <arm_group_label>Single Arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Stereotactic Body Radiation Therapy (SBRT)</intervention_name>
    <description>Patients will receive standard of care radiation therapy (SBRT)</description>
    <arm_group_label>Single Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male aged 21 years or older.&#xD;
&#xD;
          -  Ability to provide signed informed consent and willingness to comply with protocol&#xD;
             requirements.&#xD;
&#xD;
          -  Pathologic confirmation of high-risk adenocarcinoma of the prostate gland as follows:&#xD;
             a. Gleason 8-10 or tertiary component 5 disease and/or b. PSA of 20 ng/ml or greater&#xD;
             and/or c. Tumor stage of T2c or greater; OR Unfavorable intermediate risk (Gleason&#xD;
             4+3=7, &gt;50% of cores involved, or 2 or more intermediate risk factors which include&#xD;
             Gleason 7 disease, PSA 10-20, or T2b disease)&#xD;
&#xD;
          -  Participants must agree to use an acceptable form of birth control and utilize condoms&#xD;
             for a period of seven days after each PSMA injection, if engaged in sexual activity.&#xD;
&#xD;
          -  No evidence of metastatic disease, including pelvic lymph nodes.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Clinical and/or technical factors that would compromise statistical analysis of the&#xD;
             PET and/or MR.&#xD;
&#xD;
          -  Contraindications to PSMA IV administration&#xD;
&#xD;
          -  Contraindications to prostate SBRT (history of transurethral resection of prostate;&#xD;
             prostate size greater than 150 cc; AUA score greater than 20; history of prior&#xD;
             radiation to the prostate)&#xD;
&#xD;
          -  Other unspecified reasons that, in the opinion of investigators, make the subject&#xD;
             unsuitable for enrollment&#xD;
&#xD;
          -  Patients on or intending to take abiraterone will be excluded&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Male patients</gender_description>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ariel Marciscano, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Weill Medical College of Cornell University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sharanya Chandrasekhar, M.S.</last_name>
    <phone>646-962-2196</phone>
    <email>shc2043@med.cornell.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Pragya Yadav, Ph.D.</last_name>
    <phone>646-962-2199</phone>
    <email>pry2003@med.cornell.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Weill Cornell Medicine</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065'</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sharanya Chandrasekhar, M.S.</last_name>
      <phone>646-962-2196</phone>
      <email>shc2043@med.cornell.edu</email>
    </contact>
    <contact_backup>
      <last_name>Pragya Yadav, Ph.D</last_name>
      <phone>646-962-2199</phone>
      <email>pry2003@med.cornell.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Ariel Marciscano, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>May 8, 2020</study_first_submitted>
  <study_first_submitted_qc>May 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 26, 2020</study_first_posted>
  <last_update_submitted>April 17, 2023</last_update_submitted>
  <last_update_submitted_qc>April 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 19, 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>Prostatic Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT04402151
org study id: 19-10020928
secondary id: R01CA249615
nct id: NCT04402151
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: Yes
This is a single-arm Phase II clinical trial assessing the clinical efficacy of prostate
      specific membrane antigen (PSMA) PET/MR guided MR-LINAC based SBRT-SIB with planned accrual
      of 50 patients.
Localized prostate cancer can be treated in 5 sessions using a precise, targeted form of
      radiation known as stereotactic body radiation therapy (SBRT), with low toxicity. Despite
      these advances, overall outcomes for aggressive (high risk) prostate cancer remain poor, with
      10-year recurrence-free survival of approximately 65% regardless of treatment modality.
      Recurrences are typically distant and carry poor prognosis, with 5 year survival of 25%. The
      investigators propose to utilize the latest advances in cancer imaging (PSMA Positron
      Emission Tomography (PET)/Magnetic Resonance Imaging (MR)) and radiation delivery (MR-guided
      radiation therapy with real-time adaptive planning), to deliver a personalized radiation
      treatment that targets the areas of greatest risk of recurrence in the prostate with improved
      precision, and as a result improve clinical outcomes for individuals with high risk prostate
      cancer. PSMA PET/MR is a novel imaging modality, not yet widely available, that augments the
      tissue detail provided by MR. The combination of PSMA PET with MR results in improved
      delineation of intraprostatic nodules and higher diagnostic accuracy for detection of
      metastatic disease compared to conventional imaging. PSMA PET/MR imaging data is readily
      transferable to a MR-based linear accelerator (MR-LINAC), a novel, innovative platform that
      allows direct visualization of the tumor during treatment, and permits real-time
      individualized correction for motion with online adaptive radiation planning.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Clinical efficacy of prostate-specific membrane antigen (PSMA) Positron Emission Tomography (PET)/Magnetic Resonance(MR), MR-Linear Accelerator (LINAC) will be assessed by evaluating recurrence free survival
time frame: 24 months
description: Evaluate the clinical efficacy of PSMA PET/MR guided, MR-LINAC-based SBRT- SIB in high-intermediate and high risk prostate cancer, as evaluated by the 2-year recurrence-free survival rate
measure: Performance of PSMA PET/MR to MR alone at staging prostate cancer
time frame: Baseline
description: Detection of metastatic disease on each scan will be recorded, with pathologic confirmation obtained. Detection of intraprostatic nodules will be recorded with pathologic confirmation obtained.
measure: Performance of PSMA PET/MR to MR alone for identification of dominant intraprostatic nodules during radiation planning
time frame: Baseline
description: The Dominant Intraprostatic Nodules (DIN) will be defined with radiologist assistance on MR alone, and subsequently PSMA PET/MR. The incidence of alterations in target will be recorded.
measure: Compare imaging biomarkers of interest on MR and PSMA PET/MR as predictors of treatment response, versus biopsy of treatment response and PSA
time frame: Baseline
measure: Compare imaging biomarkers of interest on MR and PSMA PET/MR as predictors of treatment response, versus biopsy of treatment response and PSA
time frame: 12 months
measure: Change in Quality of life questionnaires (EPIC-26) will be assessed.
time frame: Baseline, 1month, 6months, 12 months, 18 months and 24 months.
description: Expanded Prostate Cancer Index Composite (EPIC) short form questionnaire. The Expanded Prostate Cancer Index Composite (EPIC) is a comprehensive instrument designed to evaluate patient function and bother after prostate cancer treatment. Scores range from 0 to 100, lower scores indicate worse outcomes and higher EPIC scores represent better outcomes.
measure: Change in The American Urological Association (AUA) symptom score
time frame: Baseline, 1month, 6months, 12 months, 18 months and 24 months.
description: The American Urological Association (AUA) has created this symptom index for understanding the severity of enlarged prostate symptoms. Scores ranging from 0-7 are considered to be mild symptoms, 8-19 are moderate and 20 - 35 are severe symptoms.
measure: Change in Number of Subjects with Adverse events
time frame: Baseline, 1month, 6months, 12 months and 24 months.
description: Adverse events will be collected from patients based on CTCAE version 5.0.
measure: The change in radiation doses received by the surrounding normal structures/PTV for each initial and adapted plan will be analyzed with a signed-rank Wilcoxon test (non-parametric test for paired comparisons).
time frame: Baseline, 1month
description: PTV is the planning target volume
measure: Compare the changes in the Microbiome during SBRT-SIB
time frame: Baseline
description: Gut microbiome samples will be obtained for 16S RNA analyses
measure: Compare the changes in the Microbiome during SBRT-SIB
time frame: approx. 3 weeks
description: Gut microbiome samples will be obtained for 16S RNA analyses
measure: Compare the changes in the Microbiome during SBRT-SIB
time frame: 12 months
description: Gut microbiome samples will be obtained for 16S RNA analyses
measure: Compare the immunological changes during SBRT-SIB
time frame: Baseline
description: serum samples will be obtained for immune correlate analyses
measure: Compare the immunological changes during SBRT-SIB
time frame: approx. 3 weeks
description: serum samples will be obtained for immune correlate analyses
measure: Compare the immunological changes during SBRT-SIB
time frame: 12 months
description: serum samples will be obtained for immune correlate analyses
arm group label: Single Arm
arm group type: Other
description: Patients enrolling on the protocol will undergo prostate-specific membrane antigen (PSMA) Positron Emission Tomography (PET)/Magnetic Resonance(MR) prior to start of the radiation treatment planning process. PSMA tracer is administered by IV injection and PET images are acquired.
Any patients found to have possible metastatic disease will undergo a standard of care confirmatory biopsy (if feasible) and receive treatment appropriate for their stage.
The PSMA PET/MR scan will be performed prior to initiation of androgen deprivation therapy (ADT).
intervention type: Drug
intervention name: PSMA PET/MR - Gallium-68 labeled PSMA-HBED-CC
description: Patients enrolling on the protocol will undergo prostate-specific membrane antigen (PSMA) Positron Emission Tomography (PET)/Magnetic Resonance(MR) prior to start of the radiation treatment planning process. PSMA tracer is administered by IV injection and PET images are acquired.
Any patients found to have possible metastatic disease will undergo a standard of care confirmatory biopsy (if feasible) and receive treatment appropriate for their stage.
The PSMA PET/MR scan will be performed prior to initiation of androgen deprivation therapy (ADT).
arm group label: Single Arm
intervention type: Radiation
intervention name: Stereotactic Body Radiation Therapy (SBRT)
description: Patients will receive standard of care radiation therapy (SBRT)
arm group label: Single Arm
criteria: 
gender: Male
gender based: Yes
gender description: Male patients
minimum age: 21 Years
maximum age: 90 Years
healthy volunteers: No
last name: Ariel Marciscano, M.D.
role: Principal Investigator
affiliation: Weill Medical College of Cornell University
last name: Sharanya Chandrasekhar, M.S.
phone: 646-962-2196
email: shc2043@med.cornell.edu
last name: Pragya Yadav, Ph.D.
phone: 646-962-2199
email: pry2003@med.cornell.edu
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
sharing ipd: No