<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/NCT02978586</url>
  </required_header>
  <id_info>
    <org_study_id>CASE7Y16</org_study_id>
    <nct_id>NCT02978586</nct_id>
  </id_info>
  <brief_title>A Pilot Study of [Ga-68]PSMA PET/MRI for the Assessment of PSMA-positive Tumors</brief_title>
  <official_title>A Pilot Study of [Ga-68]PSMA PET/MRI for the Assessment of PSMA-positive Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Case Comprehensive Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Case Comprehensive Cancer Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to see if positron emission tomography/ magnetic resonance&#xD;
      imaging (PET/MRI) can be used to monitor the effectiveness of cancer treatment using an&#xD;
      investigational radioactive drug called [Ga-68]PSMA.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary Objective&#xD;
&#xD;
      The primary objective of this pilot imaging study is to determine the feasibility of using&#xD;
      positron emission tomography/ magnetic resonance (PET/MR) with [Ga-68] prostate-specific&#xD;
      membrane antigen (PSMA) for staging and treatment monitoring of PSMA expressing tumors.&#xD;
      [Ga-68]PSMA PET/MR findings will be compared with standard of care imaging, patient follow&#xD;
      up, and histopathology if available. [Ga-68]PSMA PET/MR will not be used to change the&#xD;
      patients' treatment plan. Investigators will assess PET/MR test-retest reproducibility and&#xD;
      compare baseline [Ga-68]PSMA PET/MR with PET/MR after initiation (within 2-6 weeks) of&#xD;
      therapy and evaluate if [Ga-68]PSMA is a suitable biomarker for treatment monitoring and&#xD;
      assessment of early treatment response.&#xD;
&#xD;
      Secondary Objectives&#xD;
&#xD;
        -  To compare early changes in PET biomarker ([Ga-68]PSMA) tumor uptake with treatment&#xD;
           response assessed at completion of therapy (prediction of treatment response).&#xD;
&#xD;
        -  To compare changes in MRI signal intensities (multi-parametric MRI) with treatment&#xD;
           response assessed at completion of therapy.&#xD;
&#xD;
        -  To compare results from multi-parametric MR imaging with [Ga-68]PSMA uptake.&#xD;
&#xD;
        -  To assess combinations of quantitative PET and MRI metrics.&#xD;
&#xD;
      Study Design Patients, who enroll in this study, will undergo a baseline [Ga-68]PSMA PET/MR&#xD;
      to assess the level of [Ga-68]PSMA tumor uptake. Patients with positive [Ga-68]PSMA tumor&#xD;
      uptake (defined as [Ga-68]PSMA uptake twice the background activity) who are receiving&#xD;
      systemic therapy will undergo a further [Ga-68]PSMA PET/MR 2-6 weeks after start of&#xD;
      treatment. Patients with positive [Ga-68]PSMA tumor uptake will also be offered to&#xD;
      participate in a test- retest study with a 2nd [Ga-68]PSMA PET/MR prior to treatment.&#xD;
      Patients will therefore undergo a maximum of three [Ga-68]PSMA PET/MR imaging procedures. The&#xD;
      first two test-retest Ga-PSMA-PET/MRI will be performed on separate days to allow for&#xD;
      radioactive decay. There will be no other (e.g. clinically indicated) PET scan performed on&#xD;
      the same day of [Ga-68]PSMA-PET/MRI.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 14, 2018</start_date>
  <completion_date type="Actual">October 25, 2019</completion_date>
  <primary_completion_date type="Actual">October 25, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Test-retest reproducibility of PET biomarker ([Ga68]-PSMA) uptake using PET/MRI</measure>
    <time_frame>Up to 6 weeks after beginning treatment</time_frame>
    <description>The outcome measure for the statistical analysis of the test-retest reproducibility will be concordance analysis of standard uptake values (SUVs) between the 2 baseline scans</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Test-retest reproducibility of quantification of MRI sequences (multi-parametric MRI)</measure>
    <time_frame>Up to 6 weeks after beginning treatment</time_frame>
    <description>Morphologic imaging will be performed based on standard of care imaging protocols for anatomic detail and localization. Quantitative analysis will include Diffusion weighted imaging (DWI) and Dynamic contrast enhanced MRI (DCE-MRI)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ability of PET/MRI to measure changes in PET biomarker [Ga-68]PSMA) tumor uptake after initiation of therapy</measure>
    <time_frame>Up to 6 weeks after beginning treatment</time_frame>
    <description>A region of interest (ROI) will be placed in tumor lesions on the digital PET images in order to obtain Standardized Uptake Values (SUV) and/or time activity curves (TACs).&#xD;
Relative and absolute differences in tumor SUVs between pre-treatment PET vs. PET after initiation of therapy will be calculated. These differences in [Ga-68]PSMA tumor uptake will be compared with treatment response at completion of therapy (prediction of treatment response).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in MR signal intensities after initiation of therapy</measure>
    <time_frame>Up to 6 weeks after beginning treatment</time_frame>
    <description>Standard morphologic imaging will be obtained in a target area harboring tumor tissue before and after treatment. Quantitative parameters will be obtained in the respective techniques by drawing a region of interest (ROI) in the tumor lesions using dedicated post processing software and interactive workstations. Relative and absolute differences in tumor signal intensities and quantitative parameters will be calculated between pre-treatment PET vs. PET after initiation of therapy. These differences will be compared with treatment response at completion of therapy (prediction of treatment response) as assessed by standard of care imaging</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of early changes in PET biomarker ([Ga68]PSMA) tumor uptake with treatment response assessed at completion of therapy</measure>
    <time_frame>Up to 6 weeks after beginning treatment</time_frame>
    <description>Relative and absolute differences in tumor SUVs between pre-treatment PET vs. PET after initiation of therapy will be compared with treatment response at completion of therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of changes in MRI signal intensities (multi-parametric MRI) with treatment response assessed at completion of therapy</measure>
    <time_frame>Up to 6 weeks after beginning treatment</time_frame>
    <description>Relative and absolute differences in tumor MRI signal intensities and quantitative parameters as described above between pre-treatment PET vs. PET after initiation of therapy will be compared with treatment response at completion of therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of results from multi-parametric MR imaging with [Ga-68]PSMA tumor uptake</measure>
    <time_frame>Up to 6 weeks after beginning treatment</time_frame>
    <description>Changes of tumor Ga68-PSMA uptake between baseline and during treatment will be compared with changes in MR multiparametric imaging (e.g. apparent diffusion coefficient (ADC) maps, MR perfusion parameters, changes in T2* maps, etc.). The ability of each PET and MR parameter will be assessed for the ability to predict treatment response.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of combinations of quantitative PET and MRI metrics</measure>
    <time_frame>Up to 6 weeks after beginning treatment</time_frame>
    <description>Investigators will assess combinations of quantitative PET and MRI metrics regarding their ability to characterize tumors and predict treatment response. Advanced feature extraction and pattern recognition methods will be used to find a combination of fused MRI and PET features that are correlated with disease signature.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">8</enrollment>
  <condition>Prostate-specific Membrane Antigen Positive Tumors</condition>
  <condition>Prostate Cancer</condition>
  <condition>Breast Cancer</condition>
  <condition>Lung Cancer</condition>
  <arm_group>
    <arm_group_label>[Ga-68]PSMA PET/MR</arm_group_label>
    <description>Up to 3 experimental PET/MRI scans will be performed to determine the level of [Ga-68]PSMA tumor uptake</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>[Ga-68]PSMA PET/MR</intervention_name>
    <description>All participants will undergo at least 1 baseline [Ga-68]PSMA PET/MR. If participants test positive for [Ga-68]PSMA tumor uptake, they will under up to 2 additional scans</description>
    <arm_group_label>[Ga-68]PSMA PET/MR</arm_group_label>
    <other_name>PET/MRI</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients diagnosed with tumors expressing PSMA including prostate cancer, breast cancer,&#xD;
        lung cancer, renal cancer and other tumor types [Ga-68]PSMA PET/MRI known to express PSMA&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with PSMA-positive tumors including prostate cancer, breast cancer, lung&#xD;
             cancer, and other tumor types know to express PSMA&#xD;
&#xD;
          -  Patients able to tolerate PET/MRI scans&#xD;
&#xD;
          -  Informed consent must be given and signed&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects who do not meet the above mentioned inclusion criteria&#xD;
&#xD;
          -  Subjects who refuse to give and/or sign the informed consent&#xD;
&#xD;
          -  Patients who have a history of serious adverse events related to a previous MRI or&#xD;
             PET/CT&#xD;
&#xD;
          -  Patients who are unable to undergo MRI scanning due to exclusion by institutional MRI&#xD;
             restriction policies as mentioned in the standard institutional MRI informed consent&#xD;
             form&#xD;
&#xD;
          -  Patients who are currently pregnant or breast feeding. A pregnancy test within 72&#xD;
             hours of the first PET/MRI will be performed.&#xD;
&#xD;
          -  Anti-cancer treatment (chemotherapy and/or radiation therapy) within the last 2 weeks.&#xD;
&#xD;
          -  Renal insufficiency: elevated Creatinine and/or Glomerular Filtration Rate&#xD;
             (GFR)&lt;40ml/min/1.7sqm (exclusion criterion only for contrast enhanced MRI)&#xD;
&#xD;
          -  Patients with a known allergy against any component of the contrast enhancing MR agent&#xD;
             will not receive MR contrast agents. (exclusion criterion only for contrast enhanced&#xD;
             MRI)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Norbert Avril, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospitals, Case Comprehensive Cancer Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106-5065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>November 22, 2016</study_first_submitted>
  <study_first_submitted_qc>November 28, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 1, 2016</study_first_posted>
  <last_update_submitted>May 5, 2021</last_update_submitted>
  <last_update_submitted_qc>May 5, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 7, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PSMA</keyword>
  <keyword>PET/MRI</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Neoplasms</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02978586
org study id: CASE7Y16
nct id: NCT02978586
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
The purpose of this study is to see if positron emission tomography/ magnetic resonance
      imaging (PET/MRI) can be used to monitor the effectiveness of cancer treatment using an
      investigational radioactive drug called [Ga-68]PSMA.
Primary Objective

      The primary objective of this pilot imaging study is to determine the feasibility of using
      positron emission tomography/ magnetic resonance (PET/MR) with [Ga-68] prostate-specific
      membrane antigen (PSMA) for staging and treatment monitoring of PSMA expressing tumors.
      [Ga-68]PSMA PET/MR findings will be compared with standard of care imaging, patient follow
      up, and histopathology if available. [Ga-68]PSMA PET/MR will not be used to change the
      patients' treatment plan. Investigators will assess PET/MR test-retest reproducibility and
      compare baseline [Ga-68]PSMA PET/MR with PET/MR after initiation (within 2-6 weeks) of
      therapy and evaluate if [Ga-68]PSMA is a suitable biomarker for treatment monitoring and
      assessment of early treatment response.

      Secondary Objectives

        -  To compare early changes in PET biomarker ([Ga-68]PSMA) tumor uptake with treatment
           response assessed at completion of therapy (prediction of treatment response).

        -  To compare changes in MRI signal intensities (multi-parametric MRI) with treatment
           response assessed at completion of therapy.

        -  To compare results from multi-parametric MR imaging with [Ga-68]PSMA uptake.

        -  To assess combinations of quantitative PET and MRI metrics.

      Study Design Patients, who enroll in this study, will undergo a baseline [Ga-68]PSMA PET/MR
      to assess the level of [Ga-68]PSMA tumor uptake. Patients with positive [Ga-68]PSMA tumor
      uptake (defined as [Ga-68]PSMA uptake twice the background activity) who are receiving
      systemic therapy will undergo a further [Ga-68]PSMA PET/MR 2-6 weeks after start of
      treatment. Patients with positive [Ga-68]PSMA tumor uptake will also be offered to
      participate in a test- retest study with a 2nd [Ga-68]PSMA PET/MR prior to treatment.
      Patients will therefore undergo a maximum of three [Ga-68]PSMA PET/MR imaging procedures. The
      first two test-retest Ga-PSMA-PET/MRI will be performed on separate days to allow for
      radioactive decay. There will be no other (e.g. clinically indicated) PET scan performed on
      the same day of [Ga-68]PSMA-PET/MRI.
observational model: Cohort
time perspective: Prospective
measure: Test-retest reproducibility of PET biomarker ([Ga68]-PSMA) uptake using PET/MRI
time frame: Up to 6 weeks after beginning treatment
description: The outcome measure for the statistical analysis of the test-retest reproducibility will be concordance analysis of standard uptake values (SUVs) between the 2 baseline scans
measure: Test-retest reproducibility of quantification of MRI sequences (multi-parametric MRI)
time frame: Up to 6 weeks after beginning treatment
description: Morphologic imaging will be performed based on standard of care imaging protocols for anatomic detail and localization. Quantitative analysis will include Diffusion weighted imaging (DWI) and Dynamic contrast enhanced MRI (DCE-MRI)
measure: Ability of PET/MRI to measure changes in PET biomarker [Ga-68]PSMA) tumor uptake after initiation of therapy
time frame: Up to 6 weeks after beginning treatment
description: A region of interest (ROI) will be placed in tumor lesions on the digital PET images in order to obtain Standardized Uptake Values (SUV) and/or time activity curves (TACs).
Relative and absolute differences in tumor SUVs between pre-treatment PET vs. PET after initiation of therapy will be calculated. These differences in [Ga-68]PSMA tumor uptake will be compared with treatment response at completion of therapy (prediction of treatment response).
measure: Changes in MR signal intensities after initiation of therapy
time frame: Up to 6 weeks after beginning treatment
description: Standard morphologic imaging will be obtained in a target area harboring tumor tissue before and after treatment. Quantitative parameters will be obtained in the respective techniques by drawing a region of interest (ROI) in the tumor lesions using dedicated post processing software and interactive workstations. Relative and absolute differences in tumor signal intensities and quantitative parameters will be calculated between pre-treatment PET vs. PET after initiation of therapy. These differences will be compared with treatment response at completion of therapy (prediction of treatment response) as assessed by standard of care imaging
measure: Comparison of early changes in PET biomarker ([Ga68]PSMA) tumor uptake with treatment response assessed at completion of therapy
time frame: Up to 6 weeks after beginning treatment
description: Relative and absolute differences in tumor SUVs between pre-treatment PET vs. PET after initiation of therapy will be compared with treatment response at completion of therapy.
measure: Comparison of changes in MRI signal intensities (multi-parametric MRI) with treatment response assessed at completion of therapy
time frame: Up to 6 weeks after beginning treatment
description: Relative and absolute differences in tumor MRI signal intensities and quantitative parameters as described above between pre-treatment PET vs. PET after initiation of therapy will be compared with treatment response at completion of therapy.
measure: Comparison of results from multi-parametric MR imaging with [Ga-68]PSMA tumor uptake
time frame: Up to 6 weeks after beginning treatment
description: Changes of tumor Ga68-PSMA uptake between baseline and during treatment will be compared with changes in MR multiparametric imaging (e.g. apparent diffusion coefficient (ADC) maps, MR perfusion parameters, changes in T2* maps, etc.). The ability of each PET and MR parameter will be assessed for the ability to predict treatment response.
measure: Assessment of combinations of quantitative PET and MRI metrics
time frame: Up to 6 weeks after beginning treatment
description: Investigators will assess combinations of quantitative PET and MRI metrics regarding their ability to characterize tumors and predict treatment response. Advanced feature extraction and pattern recognition methods will be used to find a combination of fused MRI and PET features that are correlated with disease signature.
arm group label: [Ga-68]PSMA PET/MR
description: Up to 3 experimental PET/MRI scans will be performed to determine the level of [Ga-68]PSMA tumor uptake
intervention type: Device
intervention name: [Ga-68]PSMA PET/MR
description: All participants will undergo at least 1 baseline [Ga-68]PSMA PET/MR. If participants test positive for [Ga-68]PSMA tumor uptake, they will under up to 2 additional scans
arm group label: [Ga-68]PSMA PET/MR
other name: PET/MRI
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Norbert Avril, MD
role: Principal Investigator
affiliation: University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Prostatic Neoplasms