<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/NCT02202044</url>
  </required_header>
  <id_info>
    <org_study_id>14-1359.cc</org_study_id>
    <nct_id>NCT02202044</nct_id>
  </id_info>
  <brief_title>Sequential Intravesical Bacillus Calmette-Guérin and Electromotive Mitomycin-C After Transuretheral Resection</brief_title>
  <official_title>Adjuvant Sequential Intravesical BCG (Bacillus Calmette-Guérin) and Electromotive Mitomycin-C (EMDA/MMC) After Transuretheral Resection (TUR) in Patients With Primary High Risk Non-Muscle Invasive Transitional Cell Carcinoma of the Bladder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Colorado, Denver</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Rutgers Cancer Institute of New Jersey</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Colorado, Denver</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of the study is to assess the bladder cancer recurrence free rate,&#xD;
      according to a phase II pilot study, of intravesical instillation of sequential BCG and&#xD;
      EMDA/MMC after TUR. The study is designed as a one-sample investigation: the outcome measure&#xD;
      is disease recurrence rate. Follow up will continue up to 5 years.&#xD;
&#xD;
      For sample size determination, disease recurrence rate will be compared with literature data&#xD;
      of recurrence rate obtained in standard BCG alone administration (Lamm's protocol).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      TURBT (TransUrethral Resection of Bladder Tumor)&#xD;
&#xD;
      Prior to enrolment, all patients must sign a consent form and will have a Complete Blood&#xD;
      Count (CBC), Basic Metabolic Panel (BMP) and a Urinalysis (UA) performed. The patients White&#xD;
      Blood Count (WBC) must be greater than 4.0 10^9/L and platelet count greater than 150 10^9/L&#xD;
      to receive drug.&#xD;
&#xD;
      Week 1, 2, 4, 5, 7 and 8: BCG instillation: 50 mg wet weight (10•2±9•0x108 colony-forming&#xD;
      units) BCG Connaught substrain. Lyophilised (ie, freeze-dried) BCG are suspended in 50 ml&#xD;
      bacteriostatic-free 0.9% Sodium Chloride (NaCl) solution. After bladder draining, the&#xD;
      suspension is infused intravesically through a 14 Fr Foley catheter and retained in the&#xD;
      bladder for 60-90 min; bladder emptying is followed by catheter removal.&#xD;
&#xD;
      Week 3, 6 and 9: A Foley catheter is inserted and the bladder is carefully drained. 40 mg MMC&#xD;
      dissolved in 100 ml NaCl 0.9% solution are instilled intravesically through the electrode&#xD;
      catheter by gravity and retained in the bladder for 30 min, while 23 mA for 30 min pulsed&#xD;
      electric current is given externally. Two dispersive cathode electrodes are placed on lower&#xD;
      abdominal skin after degreasing with alcohol. The bladder is then emptied and the catheter&#xD;
      removed. Patients are assigned one course of treatment per week for 6 weeks with sequential&#xD;
      BCG and EMDA/MMC. Two BCG instillations and one EMDA/MMC instillation constitute one cycle&#xD;
      for a total of two cycles.&#xD;
&#xD;
      A CBC and basic metabolic panel (BMP) will be performed weekly and at the beginning of each&#xD;
      cycle. Prior to dosing with mitomycin C at week 3, a CBC will be performed and also at weeks&#xD;
      4 and 5 if the CBC has changed. A UA will be performed prior to each intravesicular&#xD;
      instillation.&#xD;
&#xD;
      Maintenance treatment of eMMC will be given at month 3, 4, 6, 7, 9 and 10 (after last dose of&#xD;
      BCG of the initial treatment). Maintenance of BCG will be given around month 5, 8, and 11.&#xD;
      CBC, BMP, UA, and a history/physical (H&amp;P) will be performed before each EMDA/MMC procedure.&#xD;
      UA and a H&amp;P will be performed before each BCG.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The institution was requiring extensive changes to the protocol&#xD;
  </why_stopped>
  <start_date type="Actual">February 24, 2015</start_date>
  <completion_date type="Actual">May 11, 2016</completion_date>
  <primary_completion_date type="Actual">May 11, 2016</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>To Assess Disease Recurrence Rate</measure>
    <time_frame>5 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>To Compare Complete Response Rates at 3 and 6 Months in Patients With Carcinoma in Situ.</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>To Compare the Qualitative and Quantitative Toxicities of Experimental Regimens in These Patients.</measure>
    <time_frame>5 years</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>To Assess Long-term Morbidity in the Study Group, as Defined by Requirement for Fewer TURBTs, Courses of Traditional Intravesical Therapies, and Surveillance Cystoscopies Over 5 Years (Cost-effectiveness)</measure>
    <time_frame>5 years</time_frame>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">13</enrollment>
  <condition>Bladder Carcinoma</condition>
  <arm_group>
    <arm_group_label>Intravesical BCG and EMDA/MMC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients are assigned one course of treatment per week for 6 weeks of Intravesical Intravesical BCG and EMDA/MMC</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Intravesical BCG and EMDA/MMC</intervention_name>
    <description>Patients are assigned one course of treatment per week for 6 weeks with sequential 'Intravesical instillation of sequential Bacillus Calmette-Guérin (BCG) and Electromotive Drug Administration /Mitomycin-C</description>
    <arm_group_label>Intravesical BCG and EMDA/MMC</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  After a restaging TURBT patients with histologically proven primary high grade&#xD;
             (grade3) and/or pT1 transitional cell carcinoma of the bladder, with or without pTis&#xD;
             and pTis alone are regarded as being at high risk for tumour recurrence and&#xD;
             progression.&#xD;
&#xD;
          -  Patients may enroll in this study if they are thought to have no residual disease&#xD;
             after TURBT.&#xD;
&#xD;
          -  Age 18 years or over&#xD;
&#xD;
          -  Adequate bone-marrow reserve- ECOG performance status between 0 and 2&#xD;
&#xD;
          -  Patients who are known PPD positive will be screened for active tuberculosis prior to&#xD;
             starting treatment with BCG.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  known allergy to BCG or MMC&#xD;
&#xD;
          -  prior systemic infection with BCG&#xD;
&#xD;
          -  prior or concomitant urothelial tumours of the upper urinary tract or urethra&#xD;
&#xD;
          -  previous muscle-invasive (ie, stage T2 or higher) transitional-cell carcinoma of the&#xD;
             bladder&#xD;
&#xD;
          -  bladder capacity of less than 200 ml&#xD;
&#xD;
          -  untreated urinary-tract infection&#xD;
&#xD;
          -  severe systemic infection (ie, sepsis)&#xD;
&#xD;
          -  known HIV-positivity; therapy with immunosuppressive agents&#xD;
&#xD;
          -  urethral strictures that would prevent endoscopic procedures and repeated&#xD;
             catheterisation&#xD;
&#xD;
          -  upper urinary tract disease (eg, vesicoureteral reflux or urinary-tract stones) that&#xD;
             would make multiple transurethral procedures a risk&#xD;
&#xD;
          -  previous radiotherapy to the pelvis&#xD;
&#xD;
          -  other concurrent chemotherapy&#xD;
&#xD;
          -  treatment with radiotherapy-response or biological-response modifiers&#xD;
&#xD;
          -  history of tuberculosis;&#xD;
&#xD;
          -  other malignant diseases within 5 years of trial registration (except for adequately&#xD;
             treated basal-cell or squamous cell skin cancer, in situ cervical cancer and any other&#xD;
             cancer from which patients has been disease-free for 3 years);&#xD;
&#xD;
          -  pregnancy or nursing&#xD;
&#xD;
          -  psychological, familial, sociological, or geographical factors that would preclude&#xD;
             study participation.&#xD;
&#xD;
          -  Patients with implantable or wearable electrical devices will be excluded from this&#xD;
             study.&#xD;
&#xD;
          -  Patients with active tuberculosis&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>89 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Shandra Wilson, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Colorado, Denver</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Donald Lam, MD</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado Denver</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>July 24, 2014</study_first_submitted>
  <study_first_submitted_qc>July 24, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 28, 2014</study_first_posted>
  <results_first_submitted>April 29, 2019</results_first_submitted>
  <results_first_submitted_qc>May 24, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">June 14, 2019</results_first_posted>
  <last_update_submitted>May 24, 2019</last_update_submitted>
  <last_update_submitted_qc>May 24, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 14, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Bladder Cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Urinary Bladder Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>The study was terminated before participants finished treatment and the PI is no longer in the institution to provide information for results reporting. No results information is available.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Intravesical BCG and EMDA/MMC</title>
          <description>Patients are assigned one course of treatment per week for 6 weeks of Intravesical Intravesical BCG and EMDA/MMC&#xD;
Intravesical BCG and EMDA/MMC: Patients are assigned one course of treatment per week for 6 weeks with sequential 'Intravesical instillation of sequential Bacillus Calmette-Guérin (BCG) and Electromotive Drug Administration /Mitomycin-C</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The study was terminated before participants finished treatment and the PI is no longer in the institution to provide information for results reporting. No results information is available</population>
      <group_list>
        <group group_id="B1">
          <title>Intravesical BCG and EMDA/MMC</title>
          <description>Patients are assigned one course of treatment per week for 6 weeks of Intravesical Intravesical BCG and EMDA/MMC&#xD;
Intravesical BCG and EMDA/MMC: Patients are assigned one course of treatment per week for 6 weeks with sequential 'Intravesical instillation of sequential Bacillus Calmette-Guérin (BCG) and Electromotive Drug Administration /Mitomycin-C</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="0"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                </category>
                <category>
                  <title>Male</title>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <class_list>
            <class>
              <title>United States</title>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>To Assess Disease Recurrence Rate</title>
        <time_frame>5 years</time_frame>
        <population>The study was terminated before participants finished treatment and the PI is no longer in the institution to provide information for results reporting. No results information is available.</population>
        <group_list>
          <group group_id="O1">
            <title>Intravesical BCG and EMDA/MMC</title>
            <description>Patients are assigned one course of treatment per week for 6 weeks of Intravesical Intravesical BCG and EMDA/MMC&#xD;
Intravesical BCG and EMDA/MMC: Patients are assigned one course of treatment per week for 6 weeks with sequential 'Intravesical instillation of sequential Bacillus Calmette-Guérin (BCG) and Electromotive Drug Administration /Mitomycin-C</description>
          </group>
        </group_list>
        <measure>
          <title>To Assess Disease Recurrence Rate</title>
          <population>The study was terminated before participants finished treatment and the PI is no longer in the institution to provide information for results reporting. No results information is available.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>To Compare Complete Response Rates at 3 and 6 Months in Patients With Carcinoma in Situ.</title>
        <time_frame>5 years</time_frame>
        <population>The study was terminated before participants finished treatment and the PI is no longer in the institution to provide information for results reporting. No results information is available.</population>
        <group_list>
          <group group_id="O1">
            <title>Intravesical BCG and EMDA/MMC</title>
            <description>Patients are assigned one course of treatment per week for 6 weeks of Intravesical Intravesical BCG and EMDA/MMC&#xD;
Intravesical BCG and EMDA/MMC: Patients are assigned one course of treatment per week for 6 weeks with sequential 'Intravesical instillation of sequential Bacillus Calmette-Guérin (BCG) and Electromotive Drug Administration /Mitomycin-C</description>
          </group>
        </group_list>
        <measure>
          <title>To Compare Complete Response Rates at 3 and 6 Months in Patients With Carcinoma in Situ.</title>
          <population>The study was terminated before participants finished treatment and the PI is no longer in the institution to provide information for results reporting. No results information is available.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>To Compare the Qualitative and Quantitative Toxicities of Experimental Regimens in These Patients.</title>
        <time_frame>5 years</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>To Assess Long-term Morbidity in the Study Group, as Defined by Requirement for Fewer TURBTs, Courses of Traditional Intravesical Therapies, and Surveillance Cystoscopies Over 5 Years (Cost-effectiveness)</title>
        <time_frame>5 years</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>The study was terminated before participants finished treatment and the PI is no longer in the institution to provide information for results reporting. No results information is available.</time_frame>
      <desc>The study was terminated before participants finished treatment and the PI is no longer in the institution to provide information for results reporting. No results information is available.</desc>
      <group_list>
        <group group_id="E1">
          <title>Intravesical BCG and EMDA/MMC</title>
          <description>Patients are assigned one course of treatment per week for 6 weeks of Intravesical Intravesical BCG and EMDA/MMC&#xD;
Intravesical BCG and EMDA/MMC: Patients are assigned one course of treatment per week for 6 weeks with sequential 'Intravesical instillation of sequential Bacillus Calmette-Guérin (BCG) and Electromotive Drug Administration /Mitomycin-C</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Tracey MacDermott</name_or_title>
      <organization>University of Colorado</organization>
      <phone>303-724-2757</phone>
      <email>Tracey.MacDermott@ucdenver.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02202044
org study id: 14-1359.cc
nct id: NCT02202044
lead sponsor: 
collaborator: 
has dmc: No
The primary objective of the study is to assess the bladder cancer recurrence free rate,
      according to a phase II pilot study, of intravesical instillation of sequential BCG and
      EMDA/MMC after TUR. The study is designed as a one-sample investigation: the outcome measure
      is disease recurrence rate. Follow up will continue up to 5 years.

      For sample size determination, disease recurrence rate will be compared with literature data
      of recurrence rate obtained in standard BCG alone administration (Lamm's protocol).
TURBT (TransUrethral Resection of Bladder Tumor)

      Prior to enrolment, all patients must sign a consent form and will have a Complete Blood
      Count (CBC), Basic Metabolic Panel (BMP) and a Urinalysis (UA) performed. The patients White
      Blood Count (WBC) must be greater than 4.0 10^9/L and platelet count greater than 150 10^9/L
      to receive drug.

      Week 1, 2, 4, 5, 7 and 8: BCG instillation: 50 mg wet weight (10•2±9•0x108 colony-forming
      units) BCG Connaught substrain. Lyophilised (ie, freeze-dried) BCG are suspended in 50 ml
      bacteriostatic-free 0.9% Sodium Chloride (NaCl) solution. After bladder draining, the
      suspension is infused intravesically through a 14 Fr Foley catheter and retained in the
      bladder for 60-90 min; bladder emptying is followed by catheter removal.

      Week 3, 6 and 9: A Foley catheter is inserted and the bladder is carefully drained. 40 mg MMC
      dissolved in 100 ml NaCl 0.9% solution are instilled intravesically through the electrode
      catheter by gravity and retained in the bladder for 30 min, while 23 mA for 30 min pulsed
      electric current is given externally. Two dispersive cathode electrodes are placed on lower
      abdominal skin after degreasing with alcohol. The bladder is then emptied and the catheter
      removed. Patients are assigned one course of treatment per week for 6 weeks with sequential
      BCG and EMDA/MMC. Two BCG instillations and one EMDA/MMC instillation constitute one cycle
      for a total of two cycles.

      A CBC and basic metabolic panel (BMP) will be performed weekly and at the beginning of each
      cycle. Prior to dosing with mitomycin C at week 3, a CBC will be performed and also at weeks
      4 and 5 if the CBC has changed. A UA will be performed prior to each intravesicular
      instillation.

      Maintenance treatment of eMMC will be given at month 3, 4, 6, 7, 9 and 10 (after last dose of
      BCG of the initial treatment). Maintenance of BCG will be given around month 5, 8, and 11.
      CBC, BMP, UA, and a history/physical (H&P) will be performed before each EMDA/MMC procedure.
      UA and a H&P will be performed before each BCG.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: To Assess Disease Recurrence Rate
time frame: 5 years
measure: To Compare Complete Response Rates at 3 and 6 Months in Patients With Carcinoma in Situ.
time frame: 5 years
measure: To Compare the Qualitative and Quantitative Toxicities of Experimental Regimens in These Patients.
time frame: 5 years
measure: To Assess Long-term Morbidity in the Study Group, as Defined by Requirement for Fewer TURBTs, Courses of Traditional Intravesical Therapies, and Surveillance Cystoscopies Over 5 Years (Cost-effectiveness)
time frame: 5 years
arm group label: Intravesical BCG and EMDA/MMC
arm group type: Experimental
description: Patients are assigned one course of treatment per week for 6 weeks of Intravesical Intravesical BCG and EMDA/MMC
intervention type: Device
intervention name: Intravesical BCG and EMDA/MMC
description: Patients are assigned one course of treatment per week for 6 weeks with sequential 'Intravesical instillation of sequential Bacillus Calmette-Guérin (BCG) and Electromotive Drug Administration /Mitomycin-C
arm group label: Intravesical BCG and EMDA/MMC
criteria: 
gender: All
minimum age: 18 Years
maximum age: 89 Years
healthy volunteers: No
last name: Shandra Wilson, MD
role: Principal Investigator
affiliation: University of Colorado, Denver
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Urinary Bladder Neoplasms
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 