<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/NCT03292874</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00049177</org_study_id>
    <nct_id>NCT03292874</nct_id>
  </id_info>
  <brief_title>High Resolution MRI Study for Prostate Cancer</brief_title>
  <official_title>Evaluation of a Novel High-Resolution Diffusion-Weighted MRI Sequence</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cedars-Sinai Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cedars-Sinai Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This high resolution MRI (hrMRI), along with stand MRI (sMRI) will be obtained at baseline&#xD;
      and again in approximately 1 year in patients on prostate cancer active surveillance. Changes&#xD;
      in lesion size and ADC values will be assessed on the serial studies. This study evaluates&#xD;
      the hypothesis that hrMRI will detect changes that sMRI cannot detect and that these changes&#xD;
      will correlate with prostate cancer progression as determined on prostate biopsy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      2.0 BACKGROUND AND RATIONALE&#xD;
&#xD;
      Multiparametric MRI Multiparametric MRI combining T2-weighted, diffusion-weighted, and&#xD;
      dynamic contrast enhanced (DCE) images is commonly employed for detection and localization of&#xD;
      prostate lesions. Diffusion-weighted imaging (DWI) is sensitive to the diffusion of water&#xD;
      molecules interacting with surrounding macromolecules. DWI, which provides a quantitative&#xD;
      biological parameter called apparent diffusion coefficient (ADC) value, is a robust MRI&#xD;
      parameter for differentiating benign and malignant prostate tissue. In fact, the latest&#xD;
      version of the Prostate Imaging-Reporting and Data System (PI-RADS) scoring system relies&#xD;
      almost exclusively on DWI to identify tumors in the peripheral zone, which is where the vast&#xD;
      majority of prostate cancers form. Findings on T2 images are not used to identify cancer, and&#xD;
      DCE images are only used to differentiate between some PI-RADS 3 and 4 lesions. In a pilot&#xD;
      study of prostate cancer AS, DW-MRI was useful for detecting progression of Gleason score&#xD;
      based on changes in ADC value. Tumor size is another important clinical criterion for&#xD;
      defining low risk prostate cancer, and tumor size based on DWI has been shown to crudely&#xD;
      predict low risk prostate cancer. However, conventional DWI using single-shot echo-planar&#xD;
      imaging is unable to detect small tumors, low grade tumors, or small changes in tumor size on&#xD;
      serial imaging. Approximately 20% of small, low grade tumors found in men on AS are detected&#xD;
      on modern prostate MRI.&#xD;
&#xD;
      High Resolution MRI Investigators introduce a new three-dimensional (3D) high-resolution&#xD;
      diffusion-weighted imaging sequence (HR-DWI), which improves image quality while conferring&#xD;
      at least a 5-fold improvement in resolution when compared to standard two-dimensional (2D)&#xD;
      DWI (S-DWI). This novel 3D DWI technique has been developed by our team and can be applied on&#xD;
      existing 1.5T or 3T MRI systems. S-DWI suffers from two important limitations. a) It uses&#xD;
      single-shot echo-planar imaging (EPI) for data acquisition, which produces magnetic&#xD;
      susceptibility induced streaking artifacts and geometric distortions so that round objects&#xD;
      may appear oval. b) The relatively low signal-to-noise ratio and 2D image acquisition with&#xD;
      S-DWI limit spatial resolution, which is defined by the minimum distance between two objects&#xD;
      required to resolve them uniquely. Our HR-DWI overcomes these limitations by using&#xD;
      magnetization prepared, multi-shot, turbo-spin-echo acquisition, which improves&#xD;
      signal-to-noise ratio (SNR), spatial resolution, and image quality, and eliminates geometric&#xD;
      distortions and streaking artifacts associated with EPI.&#xD;
&#xD;
      Preliminary studies&#xD;
&#xD;
      In preliminary studies assessing the performance of our HR-DWI in a prospective pilot trial&#xD;
      of prostate cancer AS patients, the technique could detect tumors not seen on S-DWI and&#xD;
      measure ADC, which correlates with grade. This is important because the long-term natural&#xD;
      history of small prostate cancers invisible to S-DWI has never been prospectively defined, in&#xD;
      part due to lack of adequate imaging technology. In the era of molecular diagnostics and&#xD;
      next-generation sequencing, an important step in understanding the biology of these lesions&#xD;
      is to develop technologies to image and characterize these lesions. Importance of HR-DWI&#xD;
      includes:&#xD;
&#xD;
        -  Better imaging will allow these lesions to be monitored serially and targeted for&#xD;
           biopsy, providing tissue for both histologic and molecular characterization.&#xD;
&#xD;
        -  Higher resolution imaging will better delineate tumor boundaries, which can improve&#xD;
           tumor staging and identify margins during partial-gland ablation by cryotherapy or high&#xD;
           intensity focused ultrasound (HIFU), which was approved in 2015 by the U.S. FDA.&#xD;
&#xD;
        -  Improved imaging resolution will allow for more accurate measurement of tumor size and&#xD;
           ADC, and detection of small changes in size or grade over time. Standard prostate DWI&#xD;
           has poor resolution; therefore, tumor growth kinetics have never been accepted as&#xD;
           clinical criteria for cancer progression while on AS. If tumor growth kinetics or&#xD;
           changes in grade determined by ADC prove prognostic, AS can rely less on serial&#xD;
           transrectal biopsies, which can lead to serious complications.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 13, 2017</start_date>
  <completion_date type="Actual">December 14, 2022</completion_date>
  <primary_completion_date type="Actual">December 14, 2022</primary_completion_date>
  <phase>N/A</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>
    <intervention_model_description>Single arm, paired imaging</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Evidence of prostate cancer disease progression</measure>
    <time_frame>3 years from baseline imaging</time_frame>
    <description>evidence of disease progression as defined by any of the following:&#xD;
Increase in Gleason score from 3 + 3 to Gleason sum 7 on biopsy&#xD;
Gleason score 4+3 on biopsy&#xD;
Gleason sum 8-10 on biopsy&#xD;
&gt; 3 Increase in number of positive cores&#xD;
Progression to nodal or bone involvement</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">56</enrollment>
  <condition>Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Paired imaging</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Single arm, paired imaging of high resolution MRI (hrMRI) and stand MRI (sMRI)</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>high resolution MRI (hrMRI)</intervention_name>
    <description>high resolution MRI (hrMRI) and standard MRI (sMRI) will be obtained at baseline and again in approximately 1 year in patients on prostate cancer active surveillance.</description>
    <arm_group_label>Paired imaging</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age over 18 years&#xD;
&#xD;
          -  Patients diagnosed with clinically localized prostate cancer&#xD;
&#xD;
          -  Low or Low-intermediate Risk Prostate cancer1 defined as:&#xD;
&#xD;
          -  Pre-operative prostate specific antigen (PSA) ≤ 20.0 ng/ml&#xD;
&#xD;
          -  Clinical stage cT1 or cT2&#xD;
&#xD;
          -  Gleason score 3+3 or 3+4&#xD;
&#xD;
          -  Patients choosing AS or already on AS as primary management strategy&#xD;
&#xD;
          -  No previous treatment for prostate cancer with radiotherapy, chemotherapy, or hormonal&#xD;
             therapy&#xD;
&#xD;
          -  No contraindications for gadolinium enhanced MRI&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  No exclusion criteria&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hyung L Kim, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cedars-Sinai Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cedars Sinai Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90048</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>September 21, 2017</study_first_submitted>
  <study_first_submitted_qc>September 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 26, 2017</study_first_posted>
  <last_update_submitted>December 14, 2022</last_update_submitted>
  <last_update_submitted_qc>December 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 16, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Cedars-Sinai Medical Center</investigator_affiliation>
    <investigator_full_name>Hyung L. Kim, MD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>prostate cancer</keyword>
  <keyword>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/NCT03292874
org study id: Pro00049177
nct id: NCT03292874
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: Yes
This high resolution MRI (hrMRI), along with stand MRI (sMRI) will be obtained at baseline
      and again in approximately 1 year in patients on prostate cancer active surveillance. Changes
      in lesion size and ADC values will be assessed on the serial studies. This study evaluates
      the hypothesis that hrMRI will detect changes that sMRI cannot detect and that these changes
      will correlate with prostate cancer progression as determined on prostate biopsy.
2.0 BACKGROUND AND RATIONALE

      Multiparametric MRI Multiparametric MRI combining T2-weighted, diffusion-weighted, and
      dynamic contrast enhanced (DCE) images is commonly employed for detection and localization of
      prostate lesions. Diffusion-weighted imaging (DWI) is sensitive to the diffusion of water
      molecules interacting with surrounding macromolecules. DWI, which provides a quantitative
      biological parameter called apparent diffusion coefficient (ADC) value, is a robust MRI
      parameter for differentiating benign and malignant prostate tissue. In fact, the latest
      version of the Prostate Imaging-Reporting and Data System (PI-RADS) scoring system relies
      almost exclusively on DWI to identify tumors in the peripheral zone, which is where the vast
      majority of prostate cancers form. Findings on T2 images are not used to identify cancer, and
      DCE images are only used to differentiate between some PI-RADS 3 and 4 lesions. In a pilot
      study of prostate cancer AS, DW-MRI was useful for detecting progression of Gleason score
      based on changes in ADC value. Tumor size is another important clinical criterion for
      defining low risk prostate cancer, and tumor size based on DWI has been shown to crudely
      predict low risk prostate cancer. However, conventional DWI using single-shot echo-planar
      imaging is unable to detect small tumors, low grade tumors, or small changes in tumor size on
      serial imaging. Approximately 20% of small, low grade tumors found in men on AS are detected
      on modern prostate MRI.

      High Resolution MRI Investigators introduce a new three-dimensional (3D) high-resolution
      diffusion-weighted imaging sequence (HR-DWI), which improves image quality while conferring
      at least a 5-fold improvement in resolution when compared to standard two-dimensional (2D)
      DWI (S-DWI). This novel 3D DWI technique has been developed by our team and can be applied on
      existing 1.5T or 3T MRI systems. S-DWI suffers from two important limitations. a) It uses
      single-shot echo-planar imaging (EPI) for data acquisition, which produces magnetic
      susceptibility induced streaking artifacts and geometric distortions so that round objects
      may appear oval. b) The relatively low signal-to-noise ratio and 2D image acquisition with
      S-DWI limit spatial resolution, which is defined by the minimum distance between two objects
      required to resolve them uniquely. Our HR-DWI overcomes these limitations by using
      magnetization prepared, multi-shot, turbo-spin-echo acquisition, which improves
      signal-to-noise ratio (SNR), spatial resolution, and image quality, and eliminates geometric
      distortions and streaking artifacts associated with EPI.

      Preliminary studies

      In preliminary studies assessing the performance of our HR-DWI in a prospective pilot trial
      of prostate cancer AS patients, the technique could detect tumors not seen on S-DWI and
      measure ADC, which correlates with grade. This is important because the long-term natural
      history of small prostate cancers invisible to S-DWI has never been prospectively defined, in
      part due to lack of adequate imaging technology. In the era of molecular diagnostics and
      next-generation sequencing, an important step in understanding the biology of these lesions
      is to develop technologies to image and characterize these lesions. Importance of HR-DWI
      includes:

        -  Better imaging will allow these lesions to be monitored serially and targeted for
           biopsy, providing tissue for both histologic and molecular characterization.

        -  Higher resolution imaging will better delineate tumor boundaries, which can improve
           tumor staging and identify margins during partial-gland ablation by cryotherapy or high
           intensity focused ultrasound (HIFU), which was approved in 2015 by the U.S. FDA.

        -  Improved imaging resolution will allow for more accurate measurement of tumor size and
           ADC, and detection of small changes in size or grade over time. Standard prostate DWI
           has poor resolution; therefore, tumor growth kinetics have never been accepted as
           clinical criteria for cancer progression while on AS. If tumor growth kinetics or
           changes in grade determined by ADC prove prognostic, AS can rely less on serial
           transrectal biopsies, which can lead to serious complications.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Single arm, paired imaging
primary purpose: Diagnostic
masking: None (Open Label)
measure: Evidence of prostate cancer disease progression
time frame: 3 years from baseline imaging
description: evidence of disease progression as defined by any of the following:
Increase in Gleason score from 3 + 3 to Gleason sum 7 on biopsy
Gleason score 4+3 on biopsy
Gleason sum 8-10 on biopsy
> 3 Increase in number of positive cores
Progression to nodal or bone involvement
arm group label: Paired imaging
arm group type: Other
description: Single arm, paired imaging of high resolution MRI (hrMRI) and stand MRI (sMRI)
intervention type: Diagnostic Test
intervention name: high resolution MRI (hrMRI)
description: high resolution MRI (hrMRI) and standard MRI (sMRI) will be obtained at baseline and again in approximately 1 year in patients on prostate cancer active surveillance.
arm group label: Paired imaging
criteria: 
gender: Male
minimum age: 19 Years
maximum age: N/A
healthy volunteers: No
last name: Hyung L Kim, MD
role: Principal Investigator
affiliation: Cedars-Sinai Medical Center
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Cedars-Sinai Medical Center
investigator full name: Hyung L. Kim, MD
investigator title: Principal Investigator
mesh term: Prostatic Neoplasms