<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/NCT02214602</url>
  </required_header>
  <id_info>
    <org_study_id>AEl-Sawy172014</org_study_id>
    <nct_id>NCT02214602</nct_id>
  </id_info>
  <brief_title>Value of Immediate Post-operative Intravesical Epirubicin in Intermediate&amp;High Risk Non Muscle Invasive Bladder Cancer</brief_title>
  <acronym>NMIBCIVT</acronym>
  <official_title>The Value of Immediate Post-operative Intravesical Epirubicin Instillation in Intermediate and High Risk Non Muscle Invasive Bladder Cancer (NMIBC): A Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mansoura University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mansoura University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of the study is to test the value of immediate post-operative intravesical&#xD;
      instillation of epirubicin in patients with intermediate and high risk non muscle invasive&#xD;
      bladder cancer (NMIBC).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Preoperative evaluation will be carried out in the form of routine laboratory investigations,&#xD;
      abdominal and pelvic US and computed tomography (CT) or magnetic resonance imaging (MRI)&#xD;
      abdomen and pelvis if necessary. Then, the patients will be subjected to complete TURBT.&#xD;
&#xD;
      The patients will be transferred to the recovery room, careful monitoring of the patients&#xD;
      will be carried out for the 1st 30 min, and then after confirming the patient eligibility for&#xD;
      enrollment in the study by exclusion of cases with hematuria and suspicious bladder&#xD;
      perforation, patients will be enrolled randomly into one of the two groups. The randomization&#xD;
      process will be performed using computer-generated simple random tables in a 1:1 ratio or by&#xD;
      the method of closed envelopes.&#xD;
&#xD;
      The 1st group will not receive intravesical instillation of epirubicin -Placebo-(control&#xD;
      group), and, the 2nd group will receive intravesical instillation of epirubicin 50 mg in 50&#xD;
      ml saline 0.9% (study group) with clamping of the urethral catheter for 1 hour after&#xD;
      instillation and during this period the patients are monitored for local or systemic adverse&#xD;
      events (acute abdomen, chills, fever, hot flushes, abdominal rigidity, hematuria after&#xD;
      de-clamping of the catheter).&#xD;
&#xD;
      Evaluation:&#xD;
&#xD;
      Intraoperative and early postoperative parameters of interest will be recorded and compared&#xD;
      between the two groups like EUA findings, tumor characteristics during cystoscopy as the&#xD;
      tumor size, site, shape, number, suspicion of CIS, post instillation adverse events, cytology&#xD;
      and biopsy results.&#xD;
&#xD;
      The patients will be discharged after removal of urethral catheter. They will be stratified&#xD;
      into either intermediate or high risk histopathologically confirmed NMIBC, followed up at the&#xD;
      outpatient clinic (OPC) and will receive adjuvant intravesical instillation of chemotherapy&#xD;
      or immunotherapy according to the European Association of Urology (EAU) guidelines for each&#xD;
      risk group. The patients will be evaluated by office cystoscopy and urine cytology at the OPC&#xD;
      after 12 weeks, and thereafter every 3 months during the first 2 years and then every 3 to 6&#xD;
      months according to the risk category.&#xD;
&#xD;
      During the follow-up period, all histopathologically confirmed tumors will be classified as&#xD;
      recurrences. Time to first recurrence will be the primary end point of the study, and the&#xD;
      length of follow-up will be defined as the time from inclusion to the last cystoscopy&#xD;
      control.&#xD;
&#xD;
      Methods of evaluation and follow-up:&#xD;
&#xD;
      All the patients will be evaluated on entry and at follow-up intervals. On study entry&#xD;
      patients will be evaluated by urinalysis, urine culture, serum creatinine, fasting blood&#xD;
      sugar level, complete blood count, chest X-ray, excretory urography (IVU) and or CT urography&#xD;
      and bladder wash for cytology. CT with contrast will be performed annually in cases of high&#xD;
      risk tumor category and when otherwise indicated. Complete TURBT of all visible tumors will&#xD;
      be conducted in all patients and the stage and grade will be determined according to the 1987&#xD;
      staging classification and World Health Organization (WHO) grading system in 1973+ 2004 WHO&#xD;
      grading system.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">May 2017</completion_date>
  <primary_completion_date type="Actual">April 2017</primary_completion_date>
  <phase>Phase 4</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>Prevention</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Recurrence, progression and/or death from cancer.</measure>
    <time_frame>within the 1st year after complete Transurethral resection of bladder tumor</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with Adverse Events as a Measure of Safety and Tolerability</measure>
    <time_frame>within 1st 24 hours following intravesical instillation of the used drug</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">240</enrollment>
  <condition>Carcinoma of Urinary Bladder, Superficial</condition>
  <arm_group>
    <arm_group_label>Study group(Epirubicin)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>in this arm -study group(Epirubicin)- : patients will receive immediate intravesical instillation of 50 mg of epirubicin in 50 ml of saline 0.9 % after 30 min after compete transurethral resection of bladder tumor</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>in this arm -control group- : patients will not receive immediate intravesical instillation of of epirubicin after compete transurethral resection of bladder tumor.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Epirubicin</intervention_name>
    <description>Experimental: Study group(Epirubicin)&#xD;
in the arm -study group(Epirubicin)- : patients will receive immediate intravesical instillation of 50 mg of epirubicin in 50 ml of saline 0.9 % after 30 min after compete transurethral resection of bladder tumor</description>
    <arm_group_label>Study group(Epirubicin)</arm_group_label>
    <other_name>Intravesical chemotherapy</other_name>
    <other_name>Doxorubicin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ability to give informed consent.&#xD;
&#xD;
          -  Patients with primary or recurrent papillary Non muscle invasive bladder cancer&#xD;
             (NMIBC).&#xD;
&#xD;
          -  Complete transurethral resection of bladder tumor(TURBT).&#xD;
&#xD;
          -  Normal cardiac, hematological, and renal functions.&#xD;
&#xD;
          -  Patients with intermediate and high risk NMIBC confirmed by histopathology.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inability to give informed consent.&#xD;
&#xD;
          -  Patients with history of previous radiotherapy or systemic chemotherapy.&#xD;
&#xD;
          -  Patients suffering from immuno-deficiency or other malignancies.&#xD;
&#xD;
          -  Patients with history of hypersensitivity reaction to epirubicin.&#xD;
&#xD;
          -  Examination under anesthesia (EUA) reveals palpable bladder mass.&#xD;
&#xD;
          -  Patients with primary, single, less than 1cm papillary bladder tumor (high likelihood&#xD;
             of being low risk).&#xD;
&#xD;
          -  Suspicion of perforation of the bladder during TURBT.&#xD;
&#xD;
          -  Patients who develop hematuria in the recovery room necessitating continuous bladder&#xD;
             wash or endoscopic haemostasis.&#xD;
&#xD;
          -  Patients with proven low risk NMIBC on histopathology.&#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>Bedeir A El-Dein, Professor</last_name>
    <role>Study Chair</role>
    <affiliation>Urology And Nephrology Center, Mansoura University, Mansoura</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Urology and Nephrology Center</name>
      <address>
        <city>Mansoura</city>
        <zip>35516</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>July 10, 2014</study_first_submitted>
  <study_first_submitted_qc>August 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 12, 2014</study_first_posted>
  <last_update_submitted>March 21, 2018</last_update_submitted>
  <last_update_submitted_qc>March 21, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">March 22, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mansoura University</investigator_affiliation>
    <investigator_full_name>Amr Abdel-Lateif El-Sawy</investigator_full_name>
    <investigator_title>Resident in Urology, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt</investigator_title>
  </responsible_party>
  <keyword>non muscle invasive bladder cancer</keyword>
  <keyword>intermediate and high risk</keyword>
  <keyword>immediate single instillation</keyword>
  <keyword>Intravesical chemotherapy</keyword>
  <keyword>Disease prevention</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Urinary Bladder Neoplasms</mesh_term>
    <mesh_term>Non-Muscle Invasive Bladder Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Epirubicin</mesh_term>
  </intervention_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/NCT02214602
org study id: AEl-Sawy172014
nct id: NCT02214602
lead sponsor: 
has dmc: Yes
The aim of the study is to test the value of immediate post-operative intravesical
      instillation of epirubicin in patients with intermediate and high risk non muscle invasive
      bladder cancer (NMIBC).
Preoperative evaluation will be carried out in the form of routine laboratory investigations,
      abdominal and pelvic US and computed tomography (CT) or magnetic resonance imaging (MRI)
      abdomen and pelvis if necessary. Then, the patients will be subjected to complete TURBT.

      The patients will be transferred to the recovery room, careful monitoring of the patients
      will be carried out for the 1st 30 min, and then after confirming the patient eligibility for
      enrollment in the study by exclusion of cases with hematuria and suspicious bladder
      perforation, patients will be enrolled randomly into one of the two groups. The randomization
      process will be performed using computer-generated simple random tables in a 1:1 ratio or by
      the method of closed envelopes.

      The 1st group will not receive intravesical instillation of epirubicin -Placebo-(control
      group), and, the 2nd group will receive intravesical instillation of epirubicin 50 mg in 50
      ml saline 0.9% (study group) with clamping of the urethral catheter for 1 hour after
      instillation and during this period the patients are monitored for local or systemic adverse
      events (acute abdomen, chills, fever, hot flushes, abdominal rigidity, hematuria after
      de-clamping of the catheter).

      Evaluation:

      Intraoperative and early postoperative parameters of interest will be recorded and compared
      between the two groups like EUA findings, tumor characteristics during cystoscopy as the
      tumor size, site, shape, number, suspicion of CIS, post instillation adverse events, cytology
      and biopsy results.

      The patients will be discharged after removal of urethral catheter. They will be stratified
      into either intermediate or high risk histopathologically confirmed NMIBC, followed up at the
      outpatient clinic (OPC) and will receive adjuvant intravesical instillation of chemotherapy
      or immunotherapy according to the European Association of Urology (EAU) guidelines for each
      risk group. The patients will be evaluated by office cystoscopy and urine cytology at the OPC
      after 12 weeks, and thereafter every 3 months during the first 2 years and then every 3 to 6
      months according to the risk category.

      During the follow-up period, all histopathologically confirmed tumors will be classified as
      recurrences. Time to first recurrence will be the primary end point of the study, and the
      length of follow-up will be defined as the time from inclusion to the last cystoscopy
      control.

      Methods of evaluation and follow-up:

      All the patients will be evaluated on entry and at follow-up intervals. On study entry
      patients will be evaluated by urinalysis, urine culture, serum creatinine, fasting blood
      sugar level, complete blood count, chest X-ray, excretory urography (IVU) and or CT urography
      and bladder wash for cytology. CT with contrast will be performed annually in cases of high
      risk tumor category and when otherwise indicated. Complete TURBT of all visible tumors will
      be conducted in all patients and the stage and grade will be determined according to the 1987
      staging classification and World Health Organization (WHO) grading system in 1973+ 2004 WHO
      grading system.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Single (Participant)
measure: Recurrence, progression and/or death from cancer.
time frame: within the 1st year after complete Transurethral resection of bladder tumor
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
time frame: within 1st 24 hours following intravesical instillation of the used drug
arm group label: Study group(Epirubicin)
arm group type: Experimental
description: in this arm -study group(Epirubicin)- : patients will receive immediate intravesical instillation of 50 mg of epirubicin in 50 ml of saline 0.9 % after 30 min after compete transurethral resection of bladder tumor
arm group label: Control group
arm group type: No Intervention
description: in this arm -control group- : patients will not receive immediate intravesical instillation of of epirubicin after compete transurethral resection of bladder tumor.
intervention type: Drug
intervention name: Epirubicin
description: Experimental: Study group(Epirubicin)
in the arm -study group(Epirubicin)- : patients will receive immediate intravesical instillation of 50 mg of epirubicin in 50 ml of saline 0.9 % after 30 min after compete transurethral resection of bladder tumor
arm group label: Study group(Epirubicin)
other name: Intravesical chemotherapy
other name: Doxorubicin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Bedeir A El-Dein, Professor
role: Study Chair
affiliation: Urology And Nephrology Center, Mansoura University, Mansoura
facility: 
country: Egypt
responsible party type: Principal Investigator
investigator affiliation: Mansoura University
investigator full name: Amr Abdel-Lateif El-Sawy
investigator title: Resident in Urology, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt
mesh term: Urinary Bladder Neoplasms
mesh term: Non-Muscle Invasive Bladder Neoplasms
mesh term: Doxorubicin
mesh term: Epirubicin