<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/NCT04442724</url>
  </required_header>
  <id_info>
    <org_study_id>IIT2017-12-Garcia-FMBRT</org_study_id>
    <secondary_id>1R01CA201709-01</secondary_id>
    <nct_id>NCT04442724</nct_id>
  </id_info>
  <brief_title>Bladder Fiducial Markers and Multiparametric-MRI (Mp-MRI) to Optimize Bladder Chemo-radiotherapy</brief_title>
  <acronym>FMBRT</acronym>
  <official_title>Bladder Fiducial Markers and Multiparametric-MRI (Mp-MRI) to Optimize Bladder Chemo-radiotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cedars-Sinai Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </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>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to examine the usefulness of implanting small 24-K gold fiducial&#xD;
      markers around a bladder tumor site, so that a Radiation Oncologist can identify the original&#xD;
      tumor location at the time of radiation treatment. Other goals of the study include assessing&#xD;
      whether a new MRI imaging technology can help with detection of bladder cancer earlier and&#xD;
      more accurately when evidence of bladder cancer is not visible by scope.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study of fiducial markers in patients with localized muscle-invasive bladder cancer will&#xD;
      enroll patients electing bladder preservation with tri-modal therapy.&#xD;
&#xD;
      24-K gold fiducial markers will be endoscopically implanted around the tumor resection area&#xD;
      to mark the location of the tumor site, into the bladder wall submucosa space under direct&#xD;
      visualization via a coaxial needle. The markers are visible on all imaging modalities,&#xD;
      including all available on-table imaging (e.g., portal and cone-beam CT) used for&#xD;
      radiotherapy. Reliable fiducial marker placement within the bladder may have the potential to&#xD;
      advance bladder-sparing management of localized muscle-invasive bladder cancer.&#xD;
&#xD;
      This study will examine the effectiveness of bladder-preserving multi-modal treatment of&#xD;
      muscle-invasive bladder cancer with and without fiducial marker placement to guide&#xD;
      radiotherapy targeting and to minimize collateral radiation. In addition, this study intends&#xD;
      to verify the accuracy and report on the sensitivity and specificity of mp-MRI imaging to&#xD;
      detect the presence and location of bladder cancer.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 1, 2020</start_date>
  <completion_date type="Anticipated">August 2023</completion_date>
  <primary_completion_date type="Anticipated">August 2023</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Bladder volume differential</measure>
    <time_frame>Baseline, after marker placement (anticipated to occur between study days 0-1)</time_frame>
    <description>Change in bladder volumes targeted for high dose radiation (HDR) between the first (Baseline) dose volume histogram (DVH) without the fiducial markers present, compared to the second DVH made after placement of the fiducial markers</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Net dose radiation to collateral organs differential</measure>
    <time_frame>Baseline, after marker placement (anticipated to occur between study days 0-1)</time_frame>
    <description>comparison of a DVH (Dose Volume Histogram) made without the fiducial markers present, to the second DVH made with the fiducial markers present. This will be measured by net dose (Gy to area and/or volume) to collateral organs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Positive Predictive Value of Multiparametric-MRI (mp-MRI)</measure>
    <time_frame>at the time of initial TURBT (Day 1), at the initial post-treatment surveillance cystoscopy (3 months post-treatment)</time_frame>
    <description>percentage of actual positive sites among those predicted positive by mpMRI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in alignment when markers are incorporated into the planning</measure>
    <time_frame>Radiotherapy treatment period (Days 14-28)</time_frame>
    <description>Difference in &quot;on-table&quot; patient alignment under the radiotherapy gantry (in millimeters, in X, Y and Z dimensions) when the patient is aligned daily based on conventional methods only (i.e. fiducial markers are not used for alignment), and when the patient is aligned based on the fiducial markers as the reference.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Bladder Cancer</condition>
  <condition>Urinary Bladder Neoplasm</condition>
  <condition>Urologic Neoplasms</condition>
  <condition>Neoplasms</condition>
  <condition>Urinary Bladder Diseases</condition>
  <arm_group>
    <arm_group_label>Single Arm - Bladder Chemo-Radiotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Fiducial marker placement &amp; cystogram during resection surgery, followed by radiation planning CT scan, mpMRI, chemo-radiation treatment; mpMRI and/or surveillance cystoscopy at 3, 6, and 9 months post-treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Fiducial marker placement</intervention_name>
    <description>placement of 24k gold fiducial markers surrounding the tumor site, at time of primary or re-staging bladder tumor resection</description>
    <arm_group_label>Single Arm - Bladder Chemo-Radiotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Multiparametric MRI (mpMRI)</intervention_name>
    <description>In this study, mp-MRI is defined as MRI that includes T1 &amp; T2 weighted sequences, diffusion weighted sequences, and Dynamic contrast enhanced (DCE) MRI sequences.</description>
    <arm_group_label>Single Arm - Bladder Chemo-Radiotherapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pathologically (histologically or cytologically) proven diagnosis of primary&#xD;
             urothelial carcinoma of the bladder. Subjects with mixed histology are required to&#xD;
             have a dominant traditional cell carcinoma (TCC) pattern.&#xD;
&#xD;
          -  Clinical stage T2-T4a, Nx, M0 considered appropriate for, and electing to receive,&#xD;
             chemoradiation of the bladder&#xD;
&#xD;
          -  Planned TURBT as part of the normal course treatment, to take place prior to the&#xD;
             initiation of chemo irradiation&#xD;
&#xD;
          -  Adequate renal function: Serum creatinine &lt; 2 mg/dL OR calculated creatinine clearance&#xD;
             (CrCl) &gt; 30ml/min&#xD;
&#xD;
          -  Ability to understand and willingness to sign a written informed consent&#xD;
&#xD;
          -  Women of child-bearing potential and men must agree to use adequate contraception&#xD;
             prior to study entry, during study participation, and for 90 days after study&#xD;
             treatment discontinuation&#xD;
&#xD;
               -  Should a woman become pregnant or suspect she is pregnant while she or her&#xD;
                  partner is participating in this study, she should inform her treating physician&#xD;
                  immediately&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with primary TCC of the ureter, urethra, or renal pelvis, without TCC of the&#xD;
             bladder, are not allowed&#xD;
&#xD;
          -  Known distant metastatic disease (e.g. pulmonary or hepatic metastases)&#xD;
&#xD;
               -  Subjects with malignant lymphadenopathy in the abdomen or pelvis considered&#xD;
                  appropriate for radical cystectomy and lymphadenectomy with the goal of complete&#xD;
                  resection of all malignant disease are allowed&#xD;
&#xD;
          -  Patients with bladder abnormalities that preclude safe placement of fiducial markers&#xD;
             (i.e. abundant large diverticuli or cellules, active or recurrent urinary infection)&#xD;
&#xD;
          -  Planned (or prior history of) definitive bladder irradiation&#xD;
&#xD;
          -  Intravesical chemo- or biologic therapy within 6 weeks of first treatment&#xD;
&#xD;
          -  Any planned neoadjuvant systemic immunotherapy. Note that prior bacille&#xD;
             Calmette-Guerin vaccine (BCG) is not an exclusion&#xD;
&#xD;
          -  Clinically significant active infection or uncontrolled medical condition that would&#xD;
             preclude participation in study&#xD;
&#xD;
          -  Pregnant or nursing women are excluded&#xD;
&#xD;
          -  Previous malignancy other than TCC that, in the opinion of the treating investigator,&#xD;
             is likely to interfere with protocol treatment&#xD;
&#xD;
          -  Individuals with severe renal failure and cannot receive MRI contrast&#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>Maurice Garcia, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cedars-Sinai Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jenny Park, MPH</last_name>
    <phone>310-423-8762</phone>
    <email>jenny.park@cshs.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Laura Sarmiento, CCRP</last_name>
    <phone>310-423-4295</phone>
    <email>laura.sarmiento@cshs.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Cedars-Sinai Medical Center (CSMC)</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90048</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>University of California Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jackie Hernandez, CCRP</last_name>
      <phone>310-267-8991</phone>
      <email>jhernandez@mednet.ucla.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Harvard School of Medicine/Massachusetts General Hospital (MGH)</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sarah Stec</last_name>
      <email>SSTEC@mgh.harvard.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>June 18, 2020</study_first_submitted>
  <study_first_submitted_qc>June 19, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 23, 2020</study_first_posted>
  <last_update_submitted>September 13, 2022</last_update_submitted>
  <last_update_submitted_qc>September 13, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 15, 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>Maurice M. Garcia</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Fiducial marker</keyword>
  <keyword>Fiducial marker guided technique</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Urinary Bladder Neoplasms</mesh_term>
    <mesh_term>Urologic Neoplasms</mesh_term>
    <mesh_term>Urinary Bladder Diseases</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/NCT04442724
org study id: IIT2017-12-Garcia-FMBRT
secondary id: 1R01CA201709-01
nct id: NCT04442724
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
The purpose of this study is to examine the usefulness of implanting small 24-K gold fiducial
      markers around a bladder tumor site, so that a Radiation Oncologist can identify the original
      tumor location at the time of radiation treatment. Other goals of the study include assessing
      whether a new MRI imaging technology can help with detection of bladder cancer earlier and
      more accurately when evidence of bladder cancer is not visible by scope.
This study of fiducial markers in patients with localized muscle-invasive bladder cancer will
      enroll patients electing bladder preservation with tri-modal therapy.

      24-K gold fiducial markers will be endoscopically implanted around the tumor resection area
      to mark the location of the tumor site, into the bladder wall submucosa space under direct
      visualization via a coaxial needle. The markers are visible on all imaging modalities,
      including all available on-table imaging (e.g., portal and cone-beam CT) used for
      radiotherapy. Reliable fiducial marker placement within the bladder may have the potential to
      advance bladder-sparing management of localized muscle-invasive bladder cancer.

      This study will examine the effectiveness of bladder-preserving multi-modal treatment of
      muscle-invasive bladder cancer with and without fiducial marker placement to guide
      radiotherapy targeting and to minimize collateral radiation. In addition, this study intends
      to verify the accuracy and report on the sensitivity and specificity of mp-MRI imaging to
      detect the presence and location of bladder cancer.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Bladder volume differential
time frame: Baseline, after marker placement (anticipated to occur between study days 0-1)
description: Change in bladder volumes targeted for high dose radiation (HDR) between the first (Baseline) dose volume histogram (DVH) without the fiducial markers present, compared to the second DVH made after placement of the fiducial markers
measure: Net dose radiation to collateral organs differential
time frame: Baseline, after marker placement (anticipated to occur between study days 0-1)
description: comparison of a DVH (Dose Volume Histogram) made without the fiducial markers present, to the second DVH made with the fiducial markers present. This will be measured by net dose (Gy to area and/or volume) to collateral organs
measure: Positive Predictive Value of Multiparametric-MRI (mp-MRI)
time frame: at the time of initial TURBT (Day 1), at the initial post-treatment surveillance cystoscopy (3 months post-treatment)
description: percentage of actual positive sites among those predicted positive by mpMRI
measure: Difference in alignment when markers are incorporated into the planning
time frame: Radiotherapy treatment period (Days 14-28)
description: Difference in "on-table" patient alignment under the radiotherapy gantry (in millimeters, in X, Y and Z dimensions) when the patient is aligned daily based on conventional methods only (i.e. fiducial markers are not used for alignment), and when the patient is aligned based on the fiducial markers as the reference.
arm group label: Single Arm - Bladder Chemo-Radiotherapy
arm group type: Experimental
description: Fiducial marker placement & cystogram during resection surgery, followed by radiation planning CT scan, mpMRI, chemo-radiation treatment; mpMRI and/or surveillance cystoscopy at 3, 6, and 9 months post-treatment.
intervention type: Procedure
intervention name: Fiducial marker placement
description: placement of 24k gold fiducial markers surrounding the tumor site, at time of primary or re-staging bladder tumor resection
arm group label: Single Arm - Bladder Chemo-Radiotherapy
intervention type: Diagnostic Test
intervention name: Multiparametric MRI (mpMRI)
description: In this study, mp-MRI is defined as MRI that includes T1 & T2 weighted sequences, diffusion weighted sequences, and Dynamic contrast enhanced (DCE) MRI sequences.
arm group label: Single Arm - Bladder Chemo-Radiotherapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Maurice Garcia, MD
role: Principal Investigator
affiliation: Cedars-Sinai Medical Center
last name: Jenny Park, MPH
phone: 310-423-8762
email: jenny.park@cshs.org
last name: Laura Sarmiento, CCRP
phone: 310-423-4295
email: laura.sarmiento@cshs.org
facility: 
status: Recruiting
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Cedars-Sinai Medical Center
investigator full name: Maurice M. Garcia
investigator title: Principal Investigator
mesh term: Neoplasms
mesh term: Urinary Bladder Neoplasms
mesh term: Urologic Neoplasms
mesh term: Urinary Bladder Diseases
sharing ipd: No