<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/NCT02233725</url>
  </required_header>
  <id_info>
    <org_study_id>H14-00830</org_study_id>
    <nct_id>NCT02233725</nct_id>
  </id_info>
  <brief_title>MRI / Ultrasound Fusion With Contrast-Enhanced Ultrasound Guidance</brief_title>
  <official_title>Pilot-Study - Incorporating Contrast-Enhanced Ultrasound (CEUS) to Real-Tim MRI / Ultrasound Fusion Imaging for Prostate Biopsies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of British Columbia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of British Columbia</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Prostate cancer is the most common cancer in men. It is most often detected by an abnormal&#xD;
      digital rectal exam or an elevated Prostate-Specific Antigen -determine by a blood test. When&#xD;
      it is suspected that someone may have prostate cancer, a biopsy is ordered. This biopsy is&#xD;
      performed by the Radiologist with ultrasound guidance through the rectum. In some patients, a&#xD;
      Magnetic Resonance Imaging (MRI) scan of the prostate may be ordered to further evaluate the&#xD;
      prostate. In some situations, the MRI and Ultrasound images will be fused (digitally merged)&#xD;
      together during the ultrasound procedure to help localize the questionable lesions. Recent&#xD;
      research has used an additional component known as a contrast agent - an intravenously&#xD;
      injected inert substance - which is identifiable by ultrasound. This inert substance is more&#xD;
      obvious in areas of increased blood flow, which is a common finding in cancerous lesions. In&#xD;
      this research project, we would like to determine whether the use of contrast-enhanced&#xD;
      ultrasound is beneficial in improving accuracy of the biopsies taken and the relative&#xD;
      correlation to the MRI/ Ultrasound-fused images.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      It is the hypothesis that cancerous lesions in the prostate will have an increased amount of&#xD;
      blood flow, and that the lesions identified under ultrasound with the benefits of&#xD;
      contrast-enhanced imaging can be correlated to the MRI Findings in real-time. A study of 50&#xD;
      patients who would be undergoing MRI/Ultrasound fusion would be selected to have contrast&#xD;
      added to their procedure. The lesions identified on MRI would then be evaluated with&#xD;
      contrast-enhanced ultrasound. The findings from the contrast study could then be correlated&#xD;
      with the MRI findings. The rest of the prostate gland would also be assessed using the&#xD;
      contrast agent for lesions not identified on the MRI imaging study. The pathology results&#xD;
      could be correlated with both the contrast study and the MRI study both independently, and in&#xD;
      conjunction with the two imaging modalities. If a correlation between highly suspicious&#xD;
      lesions on the MRI and significant flow patterns under contrast can be established, then the&#xD;
      sensitivity and specificity of contrast-enhanced ultrasound can be increased.&#xD;
&#xD;
      While MRI / Ultrasound Fusion is being shown to increase prostate cancer identification and&#xD;
      targeting for biopsy, it is a very limited modality due to the costs associated. Many sites&#xD;
      will also not have access to an MRI unit, and the fusion system is prohibitively expensive,&#xD;
      and requires specialized training to configure the system and modulate the images in&#xD;
      real-time. However, ultrasound is an in expensive modality that is readily available. If the&#xD;
      materials and methods in the utilization of contrast-enhanced ultrasounds can be correlated&#xD;
      to MRI / Ultrasound fusion, better protocols can be developed for contrast-enhanced&#xD;
      ultrasound. This more cost-effective method of identifying and targeting prostate cancer&#xD;
      could then be exported to smaller communities who would otherwise still be carrying out the&#xD;
      sextant biopsy model.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>July 2014</start_date>
  <completion_date type="Anticipated">December 2015</completion_date>
  <primary_completion_date type="Anticipated">July 2015</primary_completion_date>
  <phase>Phase 1</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>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Measure the quality and pathology results of prostate samples taken during Contrast-Enhanced Ultrasound (CEUS) with MRI/ Ultrasound fusion.</measure>
    <time_frame>1 Day</time_frame>
    <description>It is hypothesized that the introduction of the Definity contrast agent during the ultrasound biopsy will increase the accuracy of the targeting biopsy sample, as well as reduce the number of targeted biopsies of non-cancerous lesions. We will compare the MRI characteristics of the prostate lesions in question in real-time ( as the MRI and Ultrasound will be fused together ), and determine whether questionable lesions seen under MRI have increased flow dynamics</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Measure whether the use of Contrast-Enhanced Ultrasound (CEUS) on prostate cancer detection rates when incorporated with MRI / Ultrasound Fusion differs from non-CEUS prostate biopsies performed under MRI/ Ultrasound Fusion guidance</measure>
    <time_frame>1 Day</time_frame>
    <description>We will measure the number of prostate samples that are determined to be positive for prostate cancer, and compare that with a control group with similar prostate characteristic appearances.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Generate a Time Intensity Curve for prostate cancer lesions and measure the relation of that value to the MRI Apparent Diffusion Coefficient (ADC) value of the lesion.</measure>
    <time_frame>1 month</time_frame>
    <description>Ultrasound Contrast enhancement has a time component, and the measuring of the contrast uptake as a function of time will be measured to generate a Time Intensity Curve (TIC). The time to the contrast enhancement peak (TTP), intensity change from the baseline to peak (ΔI) and ΔI/TTP of the tumour and the the TIC will be correlated to the lesion's MRI Apparent Diffusion Coefficient (ADC) value.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Prostatic Neoplasms</condition>
  <arm_group>
    <arm_group_label>Definity Perflutren Suspension</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Injection of Definity Perflutren Injectable Suspension- which travels in the bloodstream throughout the body. These microbubbles are identifiable on ultrasound imaging, and studies of the liver and kidney have identified it as a useful adjunct to identifying vascular lesions. Areas of regular blood flow will not have as large a concentration of the microbubble agent as will areas that have increased blood flow and neovascularisation. It has been well documented that cancerous solid lesions undergo neovascularisation and have increased blood flow to the area.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Definity Perflutren Injectable Suspension</intervention_name>
    <description>a single dose of 10 μL/kg of the activated product by intravenous bolus injection over 30-60 seconds, followed by a 10 mL saline flush. If necessary, a second 10 μL/kg dose may be administered 5 minutes after the first injection to prolong contrast enhancement</description>
    <arm_group_label>Definity Perflutren Suspension</arm_group_label>
    <other_name>Lantheus DEFINITY</other_name>
    <other_name>FDA Application No. - (NDA) 021064</other_name>
    <other_name>Active Ingredient(s) - PERFLUTREN</other_name>
    <other_name>Strength- 6.52MG/ML</other_name>
    <other_name>Dosage Form/Route - INJECTABLE;INTRAVENOUS</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults ( aged 21 years or greater), English speaking patients&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who are unable to provide informed consent&#xD;
&#xD;
          -  Patients who have had previous reaction to any contrast agent at any point in the past&#xD;
&#xD;
          -  Patients who have had previous septic infection from prostate biopsies at any point in&#xD;
             the past&#xD;
&#xD;
          -  Patients who have a right-to-left, bi-directional, or transient right-to-left cardiac&#xD;
             shunts.&#xD;
&#xD;
          -  Patients undergoing extracorporeal shock wave lithotripsy for urinary calculi.&#xD;
&#xD;
          -  Patients with pre-existing cardiopulmonary compromise including, but not limited to,&#xD;
             acute myocardial infarction, acute coronary artery syndromes, worsening or unstable&#xD;
             congestive heart failure, serious ventricular arrhythmias or respiratory failure,&#xD;
             including patients receiving mechanical ventilation&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>25 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Christopher Eddy, BSc</last_name>
    <role>Study Director</role>
    <affiliation>VCH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Vancouver Coastal Health (VCHRI/VCHA)</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V5Z 1M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <reference>
    <citation>Maxeiner A, Fischer T, Stephan C, Cash H, Slowinski T, Kilic E, Durmus T. [Real-time MRI/US fusion-guided biopsy improves detection rates of prostate cancer in pre-biopsied patients]. Aktuelle Urol. 2014 May;45(3):197-203. doi: 10.1055/s-0034-1375682. Epub 2014 Jun 5. German.</citation>
    <PMID>24902069</PMID>
  </reference>
  <reference>
    <citation>Rifkin MD, Dahnert W, Kurtz AB. State of the art: endorectal sonography of the prostate gland. AJR Am J Roentgenol. 1990 Apr;154(4):691-700. doi: 10.2214/ajr.154.4.1690499. No abstract available.</citation>
    <PMID>1690499</PMID>
  </reference>
  <reference>
    <citation>Oyen R, Van Popel H, Van de Voorde W, Knapen P, Ameye F, Baert AL, Baert LV. [The significance of focal hypoechoic lesions in the peripheral zone of the prostate]. J Belge Radiol. 1995 Dec;78(6):356-8. Dutch.</citation>
    <PMID>8576025</PMID>
  </reference>
  <reference>
    <citation>Sibley RI, Sibley AF. Correlation of digital rectal examination, prostate specific antigen, and transrectal ultrasound in prostate carcinoma in African Americans. J Natl Med Assoc. 1997 May;89(5):318-23.</citation>
    <PMID>9170832</PMID>
  </reference>
  <reference>
    <citation>Norberg M, Egevad L, Holmberg L, Sparen P, Norlen BJ, Busch C. The sextant protocol for ultrasound-guided core biopsies of the prostate underestimates the presence of cancer. Urology. 1997 Oct;50(4):562-6. doi: 10.1016/S0090-4295(97)00306-3.</citation>
    <PMID>9338732</PMID>
  </reference>
  <reference>
    <citation>Halpern EJ, Ramey JR, Strup SE, Frauscher F, McCue P, Gomella LG. Detection of prostate carcinoma with contrast-enhanced sonography using intermittent harmonic imaging. Cancer. 2005 Dec 1;104(11):2373-83. doi: 10.1002/cncr.21440.</citation>
    <PMID>16240450</PMID>
  </reference>
  <reference>
    <citation>Mitterberger M, Pinggera GM, Horninger W, Bartsch G, Strasser H, Schafer G, Brunner A, Halpern EJ, Gradl J, Pallwein L, Frauscher F. Comparison of contrast enhanced color Doppler targeted biopsy to conventional systematic biopsy: impact on Gleason score. J Urol. 2007 Aug;178(2):464-8; discussion 468. doi: 10.1016/j.juro.2007.03.107. Epub 2007 Jun 11.</citation>
    <PMID>17561137</PMID>
  </reference>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>August 28, 2014</study_first_submitted>
  <study_first_submitted_qc>September 2, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 8, 2014</study_first_posted>
  <last_update_submitted>September 2, 2014</last_update_submitted>
  <last_update_submitted_qc>September 2, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 8, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Prostatic Neoplasms</keyword>
  <keyword>Magnetic Resonance Imaging</keyword>
  <keyword>MRI / Ultrasound Fusion</keyword>
  <keyword>Contrast-Enhanced Ultrasound (CEUS)</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/NCT02233725
org study id: H14-00830
nct id: NCT02233725
lead sponsor: 
has dmc: No
Prostate cancer is the most common cancer in men. It is most often detected by an abnormal
      digital rectal exam or an elevated Prostate-Specific Antigen -determine by a blood test. When
      it is suspected that someone may have prostate cancer, a biopsy is ordered. This biopsy is
      performed by the Radiologist with ultrasound guidance through the rectum. In some patients, a
      Magnetic Resonance Imaging (MRI) scan of the prostate may be ordered to further evaluate the
      prostate. In some situations, the MRI and Ultrasound images will be fused (digitally merged)
      together during the ultrasound procedure to help localize the questionable lesions. Recent
      research has used an additional component known as a contrast agent - an intravenously
      injected inert substance - which is identifiable by ultrasound. This inert substance is more
      obvious in areas of increased blood flow, which is a common finding in cancerous lesions. In
      this research project, we would like to determine whether the use of contrast-enhanced
      ultrasound is beneficial in improving accuracy of the biopsies taken and the relative
      correlation to the MRI/ Ultrasound-fused images.
It is the hypothesis that cancerous lesions in the prostate will have an increased amount of
      blood flow, and that the lesions identified under ultrasound with the benefits of
      contrast-enhanced imaging can be correlated to the MRI Findings in real-time. A study of 50
      patients who would be undergoing MRI/Ultrasound fusion would be selected to have contrast
      added to their procedure. The lesions identified on MRI would then be evaluated with
      contrast-enhanced ultrasound. The findings from the contrast study could then be correlated
      with the MRI findings. The rest of the prostate gland would also be assessed using the
      contrast agent for lesions not identified on the MRI imaging study. The pathology results
      could be correlated with both the contrast study and the MRI study both independently, and in
      conjunction with the two imaging modalities. If a correlation between highly suspicious
      lesions on the MRI and significant flow patterns under contrast can be established, then the
      sensitivity and specificity of contrast-enhanced ultrasound can be increased.

      While MRI / Ultrasound Fusion is being shown to increase prostate cancer identification and
      targeting for biopsy, it is a very limited modality due to the costs associated. Many sites
      will also not have access to an MRI unit, and the fusion system is prohibitively expensive,
      and requires specialized training to configure the system and modulate the images in
      real-time. However, ultrasound is an in expensive modality that is readily available. If the
      materials and methods in the utilization of contrast-enhanced ultrasounds can be correlated
      to MRI / Ultrasound fusion, better protocols can be developed for contrast-enhanced
      ultrasound. This more cost-effective method of identifying and targeting prostate cancer
      could then be exported to smaller communities who would otherwise still be carrying out the
      sextant biopsy model.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Measure the quality and pathology results of prostate samples taken during Contrast-Enhanced Ultrasound (CEUS) with MRI/ Ultrasound fusion.
time frame: 1 Day
description: It is hypothesized that the introduction of the Definity contrast agent during the ultrasound biopsy will increase the accuracy of the targeting biopsy sample, as well as reduce the number of targeted biopsies of non-cancerous lesions. We will compare the MRI characteristics of the prostate lesions in question in real-time ( as the MRI and Ultrasound will be fused together ), and determine whether questionable lesions seen under MRI have increased flow dynamics
measure: Measure whether the use of Contrast-Enhanced Ultrasound (CEUS) on prostate cancer detection rates when incorporated with MRI / Ultrasound Fusion differs from non-CEUS prostate biopsies performed under MRI/ Ultrasound Fusion guidance
time frame: 1 Day
description: We will measure the number of prostate samples that are determined to be positive for prostate cancer, and compare that with a control group with similar prostate characteristic appearances.
measure: Generate a Time Intensity Curve for prostate cancer lesions and measure the relation of that value to the MRI Apparent Diffusion Coefficient (ADC) value of the lesion.
time frame: 1 month
description: Ultrasound Contrast enhancement has a time component, and the measuring of the contrast uptake as a function of time will be measured to generate a Time Intensity Curve (TIC). The time to the contrast enhancement peak (TTP), intensity change from the baseline to peak (ΔI) and ΔI/TTP of the tumour and the the TIC will be correlated to the lesion's MRI Apparent Diffusion Coefficient (ADC) value.
arm group label: Definity Perflutren Suspension
arm group type: Active Comparator
description: Injection of Definity Perflutren Injectable Suspension- which travels in the bloodstream throughout the body. These microbubbles are identifiable on ultrasound imaging, and studies of the liver and kidney have identified it as a useful adjunct to identifying vascular lesions. Areas of regular blood flow will not have as large a concentration of the microbubble agent as will areas that have increased blood flow and neovascularisation. It has been well documented that cancerous solid lesions undergo neovascularisation and have increased blood flow to the area.
intervention type: Device
intervention name: Definity Perflutren Injectable Suspension
description: a single dose of 10 μL/kg of the activated product by intravenous bolus injection over 30-60 seconds, followed by a 10 mL saline flush. If necessary, a second 10 μL/kg dose may be administered 5 minutes after the first injection to prolong contrast enhancement
arm group label: Definity Perflutren Suspension
other name: Lantheus DEFINITY
other name: FDA Application No. - (NDA) 021064
other name: Active Ingredient(s) - PERFLUTREN
other name: Strength- 6.52MG/ML
other name: Dosage Form/Route - INJECTABLE;INTRAVENOUS
criteria: 
gender: Male
minimum age: 25 Years
maximum age: N/A
healthy volunteers: No
last name: Christopher Eddy, BSc
role: Study Director
affiliation: VCH
facility: 
country: Canada
citation: Maxeiner A, Fischer T, Stephan C, Cash H, Slowinski T, Kilic E, Durmus T. [Real-time MRI/US fusion-guided biopsy improves detection rates of prostate cancer in pre-biopsied patients]. Aktuelle Urol. 2014 May;45(3):197-203. doi: 10.1055/s-0034-1375682. Epub 2014 Jun 5. German.
PMID: 24902069
citation: Rifkin MD, Dahnert W, Kurtz AB. State of the art: endorectal sonography of the prostate gland. AJR Am J Roentgenol. 1990 Apr;154(4):691-700. doi: 10.2214/ajr.154.4.1690499. No abstract available.
PMID: 1690499
citation: Oyen R, Van Popel H, Van de Voorde W, Knapen P, Ameye F, Baert AL, Baert LV. [The significance of focal hypoechoic lesions in the peripheral zone of the prostate]. J Belge Radiol. 1995 Dec;78(6):356-8. Dutch.
PMID: 8576025
citation: Sibley RI, Sibley AF. Correlation of digital rectal examination, prostate specific antigen, and transrectal ultrasound in prostate carcinoma in African Americans. J Natl Med Assoc. 1997 May;89(5):318-23.
PMID: 9170832
citation: Norberg M, Egevad L, Holmberg L, Sparen P, Norlen BJ, Busch C. The sextant protocol for ultrasound-guided core biopsies of the prostate underestimates the presence of cancer. Urology. 1997 Oct;50(4):562-6. doi: 10.1016/S0090-4295(97)00306-3.
PMID: 9338732
citation: Halpern EJ, Ramey JR, Strup SE, Frauscher F, McCue P, Gomella LG. Detection of prostate carcinoma with contrast-enhanced sonography using intermittent harmonic imaging. Cancer. 2005 Dec 1;104(11):2373-83. doi: 10.1002/cncr.21440.
PMID: 16240450
citation: Mitterberger M, Pinggera GM, Horninger W, Bartsch G, Strasser H, Schafer G, Brunner A, Halpern EJ, Gradl J, Pallwein L, Frauscher F. Comparison of contrast enhanced color Doppler targeted biopsy to conventional systematic biopsy: impact on Gleason score. J Urol. 2007 Aug;178(2):464-8; discussion 468. doi: 10.1016/j.juro.2007.03.107. Epub 2007 Jun 11.
PMID: 17561137
responsible party type: Sponsor
mesh term: Prostatic Neoplasms