<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/NCT03238664</url>
  </required_header>
  <id_info>
    <org_study_id>4B-15-6</org_study_id>
    <secondary_id>NCI-2017-00626</secondary_id>
    <secondary_id>4B-15-6</secondary_id>
    <secondary_id>P30CA014089</secondary_id>
    <nct_id>NCT03238664</nct_id>
  </id_info>
  <brief_title>Robot-Assisted Laparoscopic High-Intensity Focused Ultrasound and Radical Cystectomy for Thermal Ablation of Muscle Invasive Cells in Patients With Bladder Tumors</brief_title>
  <official_title>Robot-Assisted Laparoscopic HIFU (High-Intensity Focused Ultrasound) of the Bladder Wall for Thermal Ablation of Muscle Invasive Cells of Bladder Tumors: Corroborating With Robot-Assisted Radical Cystectomy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Southern California</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Southern California</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This randomized pilot trial studies how well robot-assisted laparoscopic high-intensity&#xD;
      focused ultrasound works compared to robot-assisted radical cystectomy for thermal ablation&#xD;
      of muscle invasive cells in patients with bladder tumors. Laparoscopic high-intensity focused&#xD;
      ultrasound uses high frequency sound waves to deliver a strong beam to a specific part of the&#xD;
      tumor and may lower the number of tumor cells released into the blood stream compared to&#xD;
      radical cystectomy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To obtain preliminary estimates of the efficacy of laparoscopic high-intensity focused&#xD;
      ultrasound (HIFU) for the treatment of localized primary bladder cancer.&#xD;
&#xD;
      II. To estimate the change in the number of expelled circulating tumor cells (CTCs), when&#xD;
      comparing HIFU to robot-assisted radical cystectomy (RARC) alone.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate the safety and toxicity of using laparoscopic HIFU.&#xD;
&#xD;
      OUTLINE: Patients are randomized to 1 of 2 arms.&#xD;
&#xD;
      ARM A: Patients undergo pre-HIFU contrast-enhanced ultrasound (CEUS), standard of care biopsy&#xD;
      of the bladder tumor, laparoscopic HIFU, and post-HIFU CEUS. Patients then undergo standard&#xD;
      of care RARC.&#xD;
&#xD;
      ARM B: Patients undergo standard of care RARC.&#xD;
&#xD;
      After completion of study, patients are followed up at 2 weeks and 3 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    No funding&#xD;
  </why_stopped>
  <start_date type="Anticipated">January 22, 2018</start_date>
  <completion_date type="Anticipated">January 22, 2020</completion_date>
  <primary_completion_date type="Anticipated">January 22, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Complete ablation of the targeted lesion in the bladder wall assessed by histopathologic examination and Live/Dead Viability/Cytotoxicity Assay Kit of the resected specimen (Arm A)</measure>
    <time_frame>At the day of surgery</time_frame>
    <description>A Clopper-Pearson (exact) 90% confidence interval will be constructed for the probability of a successful HIFU procedure.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>CTC enumeration assessed using quantitative real-time polymerase chain reaction</measure>
    <time_frame>Up to 7 days post-surgery</time_frame>
    <description>The mean number of CTCs in each patient, as well as the difference between the two arms (possibly after log or square root transformation) will be estimated. Importantly the numbers of CTCs captured in the femoral lines will be compared to the numbers captured in the peripheral lines. Means and 90% confidence intervals will be calculated. Changes in CTC enumeration in a group that undergoes HIFU (Arm A) to a group that does not undergo HIFU (Arm B) will be observed.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events evaluated according to National Cancer Institute Criteria for Adverse Events version 4.0 (Arm A)</measure>
    <time_frame>Up to 3 months</time_frame>
    <description>The complication observed in all patents in each arm will be reported and summarized. For Arm A, focus will be on the complications that might be associated with the HIFU procedure; for Arm B, focus will be on the safety of placed a line in the femoral vein.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Infiltrating Bladder Urothelial Carcinoma</condition>
  <condition>Stage II Bladder Urothelial Carcinoma</condition>
  <condition>Transitional Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Arm A (laparoscopic HIFU, RARC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients undergo pre-HIFU CEUS, standard of care biopsy of the bladder tumor, laparoscopic HIFU, and post-HIFU CEUS. Patients then undergo standard of care RARC.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B (RARC)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients undergo standard of care RARC.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Biopsy</intervention_name>
    <description>Undergo biopsy of bladder tumor</description>
    <arm_group_label>Arm A (laparoscopic HIFU, RARC)</arm_group_label>
    <other_name>Bx</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>High-Intensity Focused Ultrasound Ablation</intervention_name>
    <description>Undergo laparoscopic HIFU</description>
    <arm_group_label>Arm A (laparoscopic HIFU, RARC)</arm_group_label>
    <other_name>HIFU</other_name>
    <other_name>high-intensity focused ultrasound therapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Arm A (laparoscopic HIFU, RARC)</arm_group_label>
    <arm_group_label>Arm B (RARC)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Radical Cystectomy</intervention_name>
    <description>Undergo RARC</description>
    <arm_group_label>Arm A (laparoscopic HIFU, RARC)</arm_group_label>
    <arm_group_label>Arm B (RARC)</arm_group_label>
    <other_name>Complete Cystectomy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Ultrasonography</intervention_name>
    <description>Undergo CEUS</description>
    <arm_group_label>Arm A (laparoscopic HIFU, RARC)</arm_group_label>
    <other_name>2-Dimensional Grayscale Ultrasound Imaging</other_name>
    <other_name>2-Dimensional Ultrasound Imaging</other_name>
    <other_name>2D-US</other_name>
    <other_name>Ultrasound</other_name>
    <other_name>Ultrasound Imaging</other_name>
    <other_name>Ultrasound Test</other_name>
    <other_name>Ultrasound, Medical</other_name>
    <other_name>US</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Must meet all inclusion and exclusion criteria&#xD;
&#xD;
          -  Presence of a muscle invasive bladder tumor(s) (T2), specific for transitional cell&#xD;
             carcinoma on pre-operative histology (i.e. biopsy or transurethral resection of&#xD;
             bladder tumor [TURBT]).&#xD;
&#xD;
          -  Presence of a single bladder tumor lesion&#xD;
&#xD;
          -  Patients are scheduled to undergo RARC at our institution&#xD;
&#xD;
          -  Subjects must have given written informed consent to agree to participate&#xD;
&#xD;
          -  Previous chemotherapy, and/or biological therapy for cancer are permitted provided&#xD;
             that the acoustic properties of the tumor were not affected, but the subject should&#xD;
             have recovered from the effects of these or of any prior surgery; chemotherapy can be&#xD;
             within 70 days of operation&#xD;
&#xD;
          -  Subjects must be free of any clinically significant disease other than cancer that&#xD;
             would interfere with the study evaluations&#xD;
&#xD;
          -  Pre-operative computed tomography (CT)/magnetic resonance imaging (MRI) abdomen and&#xD;
             pelvis within 90 days&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1500 mm^-3&#xD;
&#xD;
          -  Platelet count &gt;= 100,000 mm^-3&#xD;
&#xD;
          -  Hemoglobin &gt;= 10 g/dl&#xD;
&#xD;
          -  Prothrombin time (PT) =&lt; 1.5 times upper limit of laboratory normal (ULN)&#xD;
&#xD;
          -  Activated partial thromboplastin time =&lt; 1.5 times ULN&#xD;
&#xD;
          -  Total bilirubin &lt; 1.5 times ULN&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) =&lt; 3 times ULN&#xD;
&#xD;
          -  Alkaline phosphatase &lt; 2 times ULN, unless arising from bone&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects deemed unsuitable candidates and not medically optimized for RARC&#xD;
&#xD;
          -  Subjects with tumors lying &lt; 1 cm from sensitive structures such as the ureter,&#xD;
             prostate or adjacent bowel&#xD;
&#xD;
          -  Patients with presence of multiple bladder lesions&#xD;
&#xD;
          -  Subjects on concurrent anticoagulant, or immunosuppressive medication&#xD;
&#xD;
          -  Patients with pre-operative histologic confirmation of a bladder lesion other than&#xD;
             transitional cell carcinoma&#xD;
&#xD;
          -  Subjects on anti-cancer medication whether biologic or pharmaceutical&#xD;
&#xD;
          -  Women who are pregnant or nursing (pregnancy test to be performed within 24 hours&#xD;
             prior to HIFU treatment)&#xD;
&#xD;
          -  Subjects assessed by consultant anesthetist as unsuitable for general anesthetic&#xD;
&#xD;
          -  Absolute contraindications: venous injury at the level of the femoral veins or&#xD;
             proximally; known or suspected thrombosis of the femoral or iliac veins on the&#xD;
             proposed side of venous cannulation, ambulatory patient&#xD;
&#xD;
          -  Relative contraindications: presence of bleeding disorders; distortion of anatomy due&#xD;
             to local injury or deformity; previous long-term venous catheterization; history of&#xD;
             vasculitis; previous injection of sclerosis agents; previous radiation therapy&#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>Inderbir Gill, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Southern California</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <verification_date>December 2017</verification_date>
  <study_first_submitted>July 31, 2017</study_first_submitted>
  <study_first_submitted_qc>July 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 3, 2017</study_first_posted>
  <last_update_submitted>December 28, 2017</last_update_submitted>
  <last_update_submitted_qc>December 28, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">January 2, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Transitional Cell</mesh_term>
    <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/NCT03238664
org study id: 4B-15-6
secondary id: NCI-2017-00626
secondary id: 4B-15-6
secondary id: P30CA014089
nct id: NCT03238664
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
This randomized pilot trial studies how well robot-assisted laparoscopic high-intensity
      focused ultrasound works compared to robot-assisted radical cystectomy for thermal ablation
      of muscle invasive cells in patients with bladder tumors. Laparoscopic high-intensity focused
      ultrasound uses high frequency sound waves to deliver a strong beam to a specific part of the
      tumor and may lower the number of tumor cells released into the blood stream compared to
      radical cystectomy.
PRIMARY OBJECTIVES:

      I. To obtain preliminary estimates of the efficacy of laparoscopic high-intensity focused
      ultrasound (HIFU) for the treatment of localized primary bladder cancer.

      II. To estimate the change in the number of expelled circulating tumor cells (CTCs), when
      comparing HIFU to robot-assisted radical cystectomy (RARC) alone.

      SECONDARY OBJECTIVES:

      I. To evaluate the safety and toxicity of using laparoscopic HIFU.

      OUTLINE: Patients are randomized to 1 of 2 arms.

      ARM A: Patients undergo pre-HIFU contrast-enhanced ultrasound (CEUS), standard of care biopsy
      of the bladder tumor, laparoscopic HIFU, and post-HIFU CEUS. Patients then undergo standard
      of care RARC.

      ARM B: Patients undergo standard of care RARC.

      After completion of study, patients are followed up at 2 weeks and 3 months.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Complete ablation of the targeted lesion in the bladder wall assessed by histopathologic examination and Live/Dead Viability/Cytotoxicity Assay Kit of the resected specimen (Arm A)
time frame: At the day of surgery
description: A Clopper-Pearson (exact) 90% confidence interval will be constructed for the probability of a successful HIFU procedure.
measure: CTC enumeration assessed using quantitative real-time polymerase chain reaction
time frame: Up to 7 days post-surgery
description: The mean number of CTCs in each patient, as well as the difference between the two arms (possibly after log or square root transformation) will be estimated. Importantly the numbers of CTCs captured in the femoral lines will be compared to the numbers captured in the peripheral lines. Means and 90% confidence intervals will be calculated. Changes in CTC enumeration in a group that undergoes HIFU (Arm A) to a group that does not undergo HIFU (Arm B) will be observed.
measure: Incidence of adverse events evaluated according to National Cancer Institute Criteria for Adverse Events version 4.0 (Arm A)
time frame: Up to 3 months
description: The complication observed in all patents in each arm will be reported and summarized. For Arm A, focus will be on the complications that might be associated with the HIFU procedure; for Arm B, focus will be on the safety of placed a line in the femoral vein.
arm group label: Arm A (laparoscopic HIFU, RARC)
arm group type: Experimental
description: Patients undergo pre-HIFU CEUS, standard of care biopsy of the bladder tumor, laparoscopic HIFU, and post-HIFU CEUS. Patients then undergo standard of care RARC.
arm group label: Arm B (RARC)
arm group type: Active Comparator
description: Patients undergo standard of care RARC.
intervention type: Procedure
intervention name: Biopsy
description: Undergo biopsy of bladder tumor
arm group label: Arm A (laparoscopic HIFU, RARC)
other name: Bx
intervention type: Device
intervention name: High-Intensity Focused Ultrasound Ablation
description: Undergo laparoscopic HIFU
arm group label: Arm A (laparoscopic HIFU, RARC)
other name: HIFU
other name: high-intensity focused ultrasound therapy
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Arm A (laparoscopic HIFU, RARC)
arm group label: Arm B (RARC)
intervention type: Procedure
intervention name: Radical Cystectomy
description: Undergo RARC
arm group label: Arm A (laparoscopic HIFU, RARC)
arm group label: Arm B (RARC)
other name: Complete Cystectomy
intervention type: Device
intervention name: Ultrasonography
description: Undergo CEUS
arm group label: Arm A (laparoscopic HIFU, RARC)
other name: 2-Dimensional Grayscale Ultrasound Imaging
other name: 2-Dimensional Ultrasound Imaging
other name: 2D-US
other name: Ultrasound
other name: Ultrasound Imaging
other name: Ultrasound Test
other name: Ultrasound, Medical
other name: US
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Inderbir Gill, MD
role: Principal Investigator
affiliation: University of Southern California
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Transitional Cell
mesh term: Urinary Bladder Neoplasms