<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/NCT03298958</url>
  </required_header>
  <id_info>
    <org_study_id>HSC20170277H</org_study_id>
    <nct_id>NCT03298958</nct_id>
  </id_info>
  <brief_title>Secondary Prevention Trial of Rapamycin in Patients With Resected Non-muscle Invasive Bladder Cancer</brief_title>
  <official_title>Secondary Prevention Trial of Rapamycin in Patients With Resected Non-muscle Invasive Bladder Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of Texas Health Science Center at San Antonio</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The University of Texas Health Science Center at San Antonio</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study is a multi-site Phase 3 double-blinded randomized placebo-controlled trial.&#xD;
      Subjects are randomly assigned to receive either a placebo or oral Sirolimus: 0.5 mg daily.&#xD;
      All subjects will be treated for 2 years or until disease recurrence. Patients will undergo&#xD;
      endoscopic evaluation of the bladder every 3 months for the first 2 years following&#xD;
      enrollment and then every 6 months for an additional 2 years on study. Selection of BCG&#xD;
      immune therapy is at the discretion of the treating urologist but in general is reserved for&#xD;
      high-risk patients. Patients concurrently receiving BCG immune therapy will receive standard&#xD;
      BCG therapy including induction (weekly for 6 weeks) and maintenance (weekly for 3 weeks at 3&#xD;
      months, 6 months, and then every 6 months following tumor resection).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    No funding was received, no subjects were enrolled&#xD;
  </why_stopped>
  <start_date type="Actual">November 1, 2018</start_date>
  <completion_date type="Anticipated">May 1, 2022</completion_date>
  <primary_completion_date type="Anticipated">February 1, 2022</primary_completion_date>
  <phase>Phase 3</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>
    <intervention_model_description>When it is determined that you are eligible for the study, you will be assigned by chance (like flipping a coin) to one of 2 study groups.&#xD;
Sirolimus 0.5 mg/day for 2 years or until disease recurrence&#xD;
Placebo</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>Double-blinded for study staff (investigator) and patient</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Test the hypothesis that rapamycin 0.5 mg daily increases recurrence-free survival for patients with non-muscle invasive bladder cancer</measure>
    <time_frame>Patients are treated for 2 years or until disease relapse</time_frame>
    <description>Recurrence is defined as histologically-proven bladder cancer (stage CIS, Ta, T1 or ≥T2)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To determine effects of rapamycin on recurrence-free survival (RFS) for subgroup of patients with non-muscle invasive bladder cancer concurrently receiving BCG immune therapy.</measure>
    <time_frame>Patients are treated for 2 years or until disease relapse</time_frame>
    <description>Recurrence is defined as histologically-proven bladder cancer (stage CIS, Ta, T1 or ≥T2)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To compare the effects of rapamycin on BCG-specific immunity during treatment of non-muscle invasive bladder cancer with maintenance BCG.</measure>
    <time_frame>baseline and 6 months after registration</time_frame>
    <description>BCG antigen-specific IFN-gamma ELISPOT responses will be measured</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Bladder Cancer</condition>
  <arm_group>
    <arm_group_label>Placebo Oral Tablet</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subject will be randomized to take the Placebo once daily for 2 years or until disease recurrence</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sirolimus (Rapamycin) 0.5 mg/day for 2 years</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subject will be randomized to take Sirolimus (Rapamycin) 0.5mg once daily for 2 years or until disease recurrence</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rapamycin</intervention_name>
    <description>Subject will be randomized to one of the 2 arms</description>
    <arm_group_label>Sirolimus (Rapamycin) 0.5 mg/day for 2 years</arm_group_label>
    <other_name>Sirolimus</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Oral Tablet</intervention_name>
    <description>Subject will be randomized to one of the 2 arms</description>
    <arm_group_label>Placebo Oral Tablet</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pathologically (histologically) proven diagnosis of non-muscle invasive (Ta, Tis or&#xD;
             T1) bladder cancer within 60 days prior to enrollment&#xD;
&#xD;
          -  Be able to give informed consent&#xD;
&#xD;
          -  Be age 18 or older&#xD;
&#xD;
          -  Not be in an immunosuppressed state (e.g. HIV, use of chronic steroids)&#xD;
&#xD;
          -  Not have active, uncontrolled infections&#xD;
&#xD;
          -  Not be on agents known to alter rapamycin metabolism significantly&#xD;
&#xD;
          -  Not have a reported history of liver disease (e.g. cirrhosis)&#xD;
&#xD;
          -  Not have a prior history of non-bladder cancer unless the cancer is clinically stable&#xD;
             and not requiring active treatment except basal cell carcinoma or squamous cell&#xD;
             carcinoma of the skin.&#xD;
&#xD;
          -  Not pregnant, or taking effective contraception before rapamycin therapy, during&#xD;
             therapy and for 12 weeks after discontinuation of therapy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have muscle-invasive (≥T2) bladder cancer&#xD;
&#xD;
          -  Unable to give informed consent&#xD;
&#xD;
          -  Age &lt; 18&#xD;
&#xD;
          -  Immunosuppressed state (e.g. HIV, use of chronic steroids)&#xD;
&#xD;
          -  Active, uncontrolled infections&#xD;
&#xD;
          -  On agents known to alter rapamycin metabolism significantly&#xD;
&#xD;
          -  Another cancer requiring active treatment (except basal cell carcinoma or squamous&#xD;
             cell carcinoma of the skin)&#xD;
&#xD;
          -  Patients at risk of pregnancy who are unwilling or unable to take effective&#xD;
             contraception before rapamycin therapy, during therapy, and for 12 weeks after&#xD;
             discontinuation of therapy.&#xD;
&#xD;
          -  Individuals with a reported history of liver disease (e.g. cirrhosis)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of Texas Health Science Center at San Antonio</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2019</verification_date>
  <study_first_submitted>September 26, 2017</study_first_submitted>
  <study_first_submitted_qc>September 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 2, 2017</study_first_posted>
  <last_update_submitted>June 7, 2019</last_update_submitted>
  <last_update_submitted_qc>June 7, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 12, 2019</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>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>Sirolimus</mesh_term>
  </intervention_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/NCT03298958
org study id: HSC20170277H
nct id: NCT03298958
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The study is a multi-site Phase 3 double-blinded randomized placebo-controlled trial.
      Subjects are randomly assigned to receive either a placebo or oral Sirolimus: 0.5 mg daily.
      All subjects will be treated for 2 years or until disease recurrence. Patients will undergo
      endoscopic evaluation of the bladder every 3 months for the first 2 years following
      enrollment and then every 6 months for an additional 2 years on study. Selection of BCG
      immune therapy is at the discretion of the treating urologist but in general is reserved for
      high-risk patients. Patients concurrently receiving BCG immune therapy will receive standard
      BCG therapy including induction (weekly for 6 weeks) and maintenance (weekly for 3 weeks at 3
      months, 6 months, and then every 6 months following tumor resection).
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: When it is determined that you are eligible for the study, you will be assigned by chance (like flipping a coin) to one of 2 study groups.
Sirolimus 0.5 mg/day for 2 years or until disease recurrence
Placebo
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: Double-blinded for study staff (investigator) and patient
measure: Test the hypothesis that rapamycin 0.5 mg daily increases recurrence-free survival for patients with non-muscle invasive bladder cancer
time frame: Patients are treated for 2 years or until disease relapse
description: Recurrence is defined as histologically-proven bladder cancer (stage CIS, Ta, T1 or ≥T2)
measure: To determine effects of rapamycin on recurrence-free survival (RFS) for subgroup of patients with non-muscle invasive bladder cancer concurrently receiving BCG immune therapy.
time frame: Patients are treated for 2 years or until disease relapse
description: Recurrence is defined as histologically-proven bladder cancer (stage CIS, Ta, T1 or ≥T2)
measure: To compare the effects of rapamycin on BCG-specific immunity during treatment of non-muscle invasive bladder cancer with maintenance BCG.
time frame: baseline and 6 months after registration
description: BCG antigen-specific IFN-gamma ELISPOT responses will be measured
arm group label: Placebo Oral Tablet
arm group type: Placebo Comparator
description: Subject will be randomized to take the Placebo once daily for 2 years or until disease recurrence
arm group label: Sirolimus (Rapamycin) 0.5 mg/day for 2 years
arm group type: Active Comparator
description: Subject will be randomized to take Sirolimus (Rapamycin) 0.5mg once daily for 2 years or until disease recurrence
intervention type: Drug
intervention name: Rapamycin
description: Subject will be randomized to one of the 2 arms
arm group label: Sirolimus (Rapamycin) 0.5 mg/day for 2 years
other name: Sirolimus
intervention type: Drug
intervention name: Placebo Oral Tablet
description: Subject will be randomized to one of the 2 arms
arm group label: Placebo Oral Tablet
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Sponsor
mesh term: Urinary Bladder Neoplasms
mesh term: Non-Muscle Invasive Bladder Neoplasms
mesh term: Sirolimus
sharing ipd: No