<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/NCT01698359</url>
  </required_header>
  <id_info>
    <org_study_id>RRK4571</org_study_id>
    <nct_id>NCT01698359</nct_id>
  </id_info>
  <brief_title>Evaluation of Ultrasound Probe for Use in Bladder Radiotherapy</brief_title>
  <official_title>Evaluation of Ultrasound Probe for Use in Adaptive Bladder Radiotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital Birmingham NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital Birmingham NHS Foundation Trust</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Muscle-invasive bladder cancer affects over 3,000 new patients in the UK each year and&#xD;
      radiotherapy comprises a key part of the treatment pathway for many of them. Bladder&#xD;
      radiotherapy in the UK involves delivery of radiation to the entire bladder volume and aims&#xD;
      to deliver a high dose to the bladder while sparing nearby healthy organs (e.g. the bowel).&#xD;
      Unfortunately, large variations in bladder shape and volume are observed throughout treatment&#xD;
      that compromise the probability of a positive outcome for the patient, either by increasing&#xD;
      the risk of side-effects or by reducing the likelihood of adequately treating the disease.&#xD;
&#xD;
      In recent years, the implementation of 'adaptive' bladder radiotherapy strategies has&#xD;
      increased. These techniques allow modification of the treatment based on the observed&#xD;
      variations in bladder shape and volume. However, these strategies often rely on daily X-ray&#xD;
      imaging of the patient prior to treatment, which is time-consuming and associated with a&#xD;
      small risk of inducing a cancer in the patient.&#xD;
&#xD;
      This study will evaluate the potential of a commercially available ultrasound probe for use&#xD;
      as an alternative to X-ray scanning during treatment for these patients. The study will also&#xD;
      aim to compare the likelihood of reducing side-effects and successfully treating the disease&#xD;
      for the different adaptive strategies that are used around the world.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      All experiments and data analysis will be performed in the Magnetic Resonance Imaging (MRI)&#xD;
      and Radiotherapy departments respectively, at the Queen Elizabeth Hospital.&#xD;
&#xD;
      Five volunteers will be recruited to this study. They will each be required to follow a&#xD;
      documented drinking protocol prior to each of three scan sessions. The drinking protocol is&#xD;
      specific to this study and will not be intended for use with patients. To address the primary&#xD;
      endpoint of the study (i.e. the precision of the ultrasound probe for measurement of bladder&#xD;
      volume), measurement of a wide range of bladder volumes is required. In order to address this&#xD;
      aim while making efficient use of the limited available MRI scanner time, the drinking&#xD;
      protocol has been designed such that the volunteer will begin each scan session with an empty&#xD;
      bladder and finish it with a full bladder. To this end, each volunteer will be required to&#xD;
      void their bladder upon arrival and then consume 500ml of water immediately prior to the&#xD;
      start of the scan session.&#xD;
&#xD;
      Each volunteer will then be positioned on the scanner couch according to the same protocol&#xD;
      used for patients and alternate MRI and ultrasound scans will then be acquired. Given the&#xD;
      time required for each scan it is anticipated that five MRI scans and fifteen ultrasound&#xD;
      scans (three scans at a time to reduce the noise on the results, i.e. ultimately giving five&#xD;
      ultrasound bladder volume measurements) will be acquired in each session. Each volunteer will&#xD;
      be asked to attend for three sessions over the course of a number of weeks so that the&#xD;
      repeatability of bladder filling patterns can be determined.&#xD;
&#xD;
      Data processing and analysis&#xD;
&#xD;
      The volume measurements from the ultrasound probe will be recorded and each of the MRI images&#xD;
      will be exported to the Radiotherapy department where the bladder volume will be determined.&#xD;
      The precise timings of all scan acquisitions will be recorded during the imaging session.&#xD;
      Bladder volumes measured by the ultrasound probe, which can be read instantly, will be&#xD;
      recorded during the session. To evaluate the primary endpoint, the precision and accuracy of&#xD;
      the ultrasound probe will be quantified by comparing the measured values to those expected&#xD;
      from the MRI volumes. Each volume measurement from the MRI scans will be checked by a second&#xD;
      observer to minimise any associated researcher error.&#xD;
&#xD;
      To evaluate the secondary endpoint, the imaging protocol described above will provide up to&#xD;
      15 MRI images for each volunteer that can be used to inform a comparison of the different&#xD;
      adaptive strategies. However, since patients are always asked to empty their bladder prior to&#xD;
      radiotherapy treatment (in order to minimise the volume that receives radiation), the&#xD;
      deliberately wide-ranging bladder volumes that will have been measured in this study will not&#xD;
      be representative of those that would be observed in clinical practice. To address this&#xD;
      problem, a suitable dataset that quantifies the distribution of bladder volumes encountered&#xD;
      in a typical patient cohort will be used (Christie dataset, permission obtained.Software will&#xD;
      be written to randomly assign a bladder volume to each day of each volunteer's 'treatment'.&#xD;
      The MRI scan from that volunteer that most closely corresponds to the selected volume will&#xD;
      then be assigned for that day's treatment. This will be repeated for the full 20 days of&#xD;
      treatment and the importance of each MRI scan can then be factored into the results analysis&#xD;
      accordingly.&#xD;
&#xD;
      The treatment planning system within the Radiotherapy department will then be used with the&#xD;
      MRI scans to simulate a range of different 'treatments' according to each of the different&#xD;
      adaptive bladder radiotherapy strategies to be compared. The different strategies are&#xD;
      summarised here:&#xD;
&#xD;
        -  Conventional strategy: This is the current standard treatment, in which the patient plan&#xD;
           is prepared based on an initial CT scan of the patient with an empty bladder and no&#xD;
           account is made of subsequent daily variations in bladder shape and volume.&#xD;
&#xD;
        -  Plan-of-the-day strategy: Based on an initial CT scan of the patient with an empty&#xD;
           bladder, three different treatment plans are created based on an assumption of how the&#xD;
           bladder might expand. These are intended to simulate empty, partially full and full&#xD;
           bladders. The patient is scanned before treatment each day and the most appropriate plan&#xD;
           is selected for treatment.&#xD;
&#xD;
        -  Dynamic strategy: Three different treatment plans are created based on a series of&#xD;
           initial CT scans of the patient with empty, partially full and full bladder. These would&#xD;
           be expected to directly represent the empty, partially full and full bladders for the&#xD;
           individual patient. The patient is scanned before treatment each day and the most&#xD;
           appropriate plan is selected for treatment.&#xD;
&#xD;
        -  Composite strategy: The patient is CT scanned with an empty bladder and treated&#xD;
           according to the Conventional strategy for the first 7 days of treatment with daily&#xD;
           imaging. The first 5 daily scans of the patient are used to generate plans based on&#xD;
           small, partially full and full bladder. From the 8th day of treatment the daily image is&#xD;
           used to select which of these plans is appropriate for treatment.&#xD;
&#xD;
      Data processing of the MRI scans will be carried out retrospectively. The MRI scans will be&#xD;
      anonymised and exported to the Radiotherapy department. The data will then be used to (i)&#xD;
      acquire bladder volume information to compare with that acquired from the ultrasound probe&#xD;
      and (ii) prepare and evaluate radiotherapy treatment simulations to investigate the benefits&#xD;
      of different adaptive bladder radiotherapy strategies&#xD;
&#xD;
      Comparison of different adaptive techniques will focus on how much radiation is received by&#xD;
      the bowel and the extent to which the radiation misses the disease on any day of treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>November 2012</start_date>
  <completion_date type="Anticipated">October 2013</completion_date>
  <primary_completion_date type="Anticipated">July 2013</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Accuracy of ultrasound measurement of bladder volume in comparision with gold standard MRI measurement</measure>
    <time_frame>Three weeks</time_frame>
    <description>The principal aim of this study is to quantify the accuracy of ultrasound measurement of bladder volume in comparision with gold standard MRI measurement. To do this, each of the five volunteers will have 5 repeat measurements of each imaging modality (ultrasound and MRI) within each 45 minute scan session as the bladder volume increases in response to the specified drinking protocol. Each volunteer will undergo three scan sessions over three weeks. Study participants will not receive follow-up. An accuracy of +/-10% would be considered sufficient to inform future studies.</description>
  </primary_outcome>
  <enrollment type="Anticipated">5</enrollment>
  <condition>Bladder Cancer</condition>
  <eligibility>
    <study_pop>
      <textblock>
        Healthy volunteers from within the staff of the Radiotherapy, Medical Physics and Oncology&#xD;
        departments at the Queen Elizabeth Hospital&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy volunteers&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pre-existing bladder conditions&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anjali Zarkar, FRCR</last_name>
    <role>Principal Investigator</role>
    <affiliation>UHB</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Gareth Webster, PhD</last_name>
    <phone>+44 (0) 121 37 1 5056</phone>
    <email>Gareth.Webster@uhb.nhs.uk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>anjali Zarkar, FRCR</last_name>
    <phone>0121 371 3559</phone>
    <email>anjali.zarkar@uhb.nhs.uk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University hospital Birmingham</name>
      <address>
        <city>Birmingham</city>
        <state>west Midlands</state>
        <zip>B15 2TH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <investigator>
      <last_name>Anjali Zarkar, FRCR MD MBBS</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>September 2012</verification_date>
  <study_first_submitted>September 17, 2012</study_first_submitted>
  <study_first_submitted_qc>September 28, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 3, 2012</study_first_posted>
  <last_update_submitted>September 28, 2012</last_update_submitted>
  <last_update_submitted_qc>September 28, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 3, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Hospital Birmingham NHS Foundation Trust</investigator_affiliation>
    <investigator_full_name>Dr Anjali Zarkar</investigator_full_name>
    <investigator_title>Consultant Clinical Oncologist</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Urinary Bladder 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/NCT01698359
org study id: RRK4571
nct id: NCT01698359
lead sponsor: 
has dmc: No
Muscle-invasive bladder cancer affects over 3,000 new patients in the UK each year and
      radiotherapy comprises a key part of the treatment pathway for many of them. Bladder
      radiotherapy in the UK involves delivery of radiation to the entire bladder volume and aims
      to deliver a high dose to the bladder while sparing nearby healthy organs (e.g. the bowel).
      Unfortunately, large variations in bladder shape and volume are observed throughout treatment
      that compromise the probability of a positive outcome for the patient, either by increasing
      the risk of side-effects or by reducing the likelihood of adequately treating the disease.

      In recent years, the implementation of 'adaptive' bladder radiotherapy strategies has
      increased. These techniques allow modification of the treatment based on the observed
      variations in bladder shape and volume. However, these strategies often rely on daily X-ray
      imaging of the patient prior to treatment, which is time-consuming and associated with a
      small risk of inducing a cancer in the patient.

      This study will evaluate the potential of a commercially available ultrasound probe for use
      as an alternative to X-ray scanning during treatment for these patients. The study will also
      aim to compare the likelihood of reducing side-effects and successfully treating the disease
      for the different adaptive strategies that are used around the world.
All experiments and data analysis will be performed in the Magnetic Resonance Imaging (MRI)
      and Radiotherapy departments respectively, at the Queen Elizabeth Hospital.

      Five volunteers will be recruited to this study. They will each be required to follow a
      documented drinking protocol prior to each of three scan sessions. The drinking protocol is
      specific to this study and will not be intended for use with patients. To address the primary
      endpoint of the study (i.e. the precision of the ultrasound probe for measurement of bladder
      volume), measurement of a wide range of bladder volumes is required. In order to address this
      aim while making efficient use of the limited available MRI scanner time, the drinking
      protocol has been designed such that the volunteer will begin each scan session with an empty
      bladder and finish it with a full bladder. To this end, each volunteer will be required to
      void their bladder upon arrival and then consume 500ml of water immediately prior to the
      start of the scan session.

      Each volunteer will then be positioned on the scanner couch according to the same protocol
      used for patients and alternate MRI and ultrasound scans will then be acquired. Given the
      time required for each scan it is anticipated that five MRI scans and fifteen ultrasound
      scans (three scans at a time to reduce the noise on the results, i.e. ultimately giving five
      ultrasound bladder volume measurements) will be acquired in each session. Each volunteer will
      be asked to attend for three sessions over the course of a number of weeks so that the
      repeatability of bladder filling patterns can be determined.

      Data processing and analysis

      The volume measurements from the ultrasound probe will be recorded and each of the MRI images
      will be exported to the Radiotherapy department where the bladder volume will be determined.
      The precise timings of all scan acquisitions will be recorded during the imaging session.
      Bladder volumes measured by the ultrasound probe, which can be read instantly, will be
      recorded during the session. To evaluate the primary endpoint, the precision and accuracy of
      the ultrasound probe will be quantified by comparing the measured values to those expected
      from the MRI volumes. Each volume measurement from the MRI scans will be checked by a second
      observer to minimise any associated researcher error.

      To evaluate the secondary endpoint, the imaging protocol described above will provide up to
      15 MRI images for each volunteer that can be used to inform a comparison of the different
      adaptive strategies. However, since patients are always asked to empty their bladder prior to
      radiotherapy treatment (in order to minimise the volume that receives radiation), the
      deliberately wide-ranging bladder volumes that will have been measured in this study will not
      be representative of those that would be observed in clinical practice. To address this
      problem, a suitable dataset that quantifies the distribution of bladder volumes encountered
      in a typical patient cohort will be used (Christie dataset, permission obtained.Software will
      be written to randomly assign a bladder volume to each day of each volunteer's 'treatment'.
      The MRI scan from that volunteer that most closely corresponds to the selected volume will
      then be assigned for that day's treatment. This will be repeated for the full 20 days of
      treatment and the importance of each MRI scan can then be factored into the results analysis
      accordingly.

      The treatment planning system within the Radiotherapy department will then be used with the
      MRI scans to simulate a range of different 'treatments' according to each of the different
      adaptive bladder radiotherapy strategies to be compared. The different strategies are
      summarised here:

        -  Conventional strategy: This is the current standard treatment, in which the patient plan
           is prepared based on an initial CT scan of the patient with an empty bladder and no
           account is made of subsequent daily variations in bladder shape and volume.

        -  Plan-of-the-day strategy: Based on an initial CT scan of the patient with an empty
           bladder, three different treatment plans are created based on an assumption of how the
           bladder might expand. These are intended to simulate empty, partially full and full
           bladders. The patient is scanned before treatment each day and the most appropriate plan
           is selected for treatment.

        -  Dynamic strategy: Three different treatment plans are created based on a series of
           initial CT scans of the patient with empty, partially full and full bladder. These would
           be expected to directly represent the empty, partially full and full bladders for the
           individual patient. The patient is scanned before treatment each day and the most
           appropriate plan is selected for treatment.

        -  Composite strategy: The patient is CT scanned with an empty bladder and treated
           according to the Conventional strategy for the first 7 days of treatment with daily
           imaging. The first 5 daily scans of the patient are used to generate plans based on
           small, partially full and full bladder. From the 8th day of treatment the daily image is
           used to select which of these plans is appropriate for treatment.

      Data processing of the MRI scans will be carried out retrospectively. The MRI scans will be
      anonymised and exported to the Radiotherapy department. The data will then be used to (i)
      acquire bladder volume information to compare with that acquired from the ultrasound probe
      and (ii) prepare and evaluate radiotherapy treatment simulations to investigate the benefits
      of different adaptive bladder radiotherapy strategies

      Comparison of different adaptive techniques will focus on how much radiation is received by
      the bowel and the extent to which the radiation misses the disease on any day of treatment.
time perspective: Prospective
measure: Accuracy of ultrasound measurement of bladder volume in comparision with gold standard MRI measurement
time frame: Three weeks
description: The principal aim of this study is to quantify the accuracy of ultrasound measurement of bladder volume in comparision with gold standard MRI measurement. To do this, each of the five volunteers will have 5 repeat measurements of each imaging modality (ultrasound and MRI) within each 45 minute scan session as the bladder volume increases in response to the specified drinking protocol. Each volunteer will undergo three scan sessions over three weeks. Study participants will not receive follow-up. An accuracy of +/-10% would be considered sufficient to inform future studies.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Anjali Zarkar, FRCR
role: Principal Investigator
affiliation: UHB
last name: Gareth Webster, PhD
phone: +44 (0) 121 37 1 5056
email: Gareth.Webster@uhb.nhs.uk
last name: anjali Zarkar, FRCR
phone: 0121 371 3559
email: anjali.zarkar@uhb.nhs.uk
facility: 
investigator: 
country: United Kingdom
responsible party type: Principal Investigator
investigator affiliation: University Hospital Birmingham NHS Foundation Trust
investigator full name: Dr Anjali Zarkar
investigator title: Consultant Clinical Oncologist
mesh term: Urinary Bladder Neoplasms