<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/NCT04428554</url>
  </required_header>
  <id_info>
    <org_study_id>19 URO 15</org_study_id>
    <nct_id>NCT04428554</nct_id>
  </id_info>
  <brief_title>Consolidative Radiotherapy for Metastatic Urothelial Bladder Cancer Patients Without Progression and With no More Than Three Residual Metastatic Lesions Following First Line Systemic Therapy</brief_title>
  <acronym>BLAD-RAD01</acronym>
  <official_title>Consolidative Radiotherapy for Metastatic Urothelial Bladder Cancer Patients Without Progression and With no More Than Three Residual Metastatic Lesions Following First Line Systemic Therapy: a Prospective Randomized Comparative Phase II Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institut Claudius Regaud</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Institut Claudius Regaud</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase II, multicenter, randomized open-label and comparative study designed to&#xD;
      evaluate whether local consolidative radiotherapy plus standard of care improves overall&#xD;
      survival as compared to standard of care in patients with limited metastatic urothelial&#xD;
      bladder cancer and without progression following the initial phase of first-line systemic&#xD;
      therapy.&#xD;
&#xD;
      Each patient will be followed during 4 years from the date of randomization.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 30, 2020</start_date>
  <completion_date type="Anticipated">July 2028</completion_date>
  <primary_completion_date type="Anticipated">July 2028</primary_completion_date>
  <phase>Phase 2</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>Overall Survival</measure>
    <time_frame>4 years for each patient</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>4 years for each patient</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety will be assessed by the toxicity grading of the National Cancer Institute (NCI-CTCAE v5)</measure>
    <time_frame>4 years for each patient</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life will be evaluated by the EORTC QLQ-C-30 questionnaire</measure>
    <time_frame>4 years for each patient</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">130</enrollment>
  <condition>Urothelial Bladder Cancer</condition>
  <arm_group>
    <arm_group_label>Control arm</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Standard of care</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Experimental arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Experimental arm</intervention_name>
    <description>Consolidative radiotherapy (pelvic irradiation and/or metastases irradiation) + standard of care +/- previous transurethral resection of bladder tumor</description>
    <arm_group_label>Experimental arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥ 18 years&#xD;
&#xD;
          2. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2&#xD;
&#xD;
          3. Urothelial bladder cancer histologically proven (both pure urothelial cancers and&#xD;
             mixed histologic features are allowed)&#xD;
&#xD;
          4. Metastatic patients (AJCC v8: M1a or M1b) documented with contrast-enhanced CT-scanner&#xD;
             of the chest, abdomen and pelvis, either de novo or presenting first distant relapse&#xD;
             following cystectomy (with no local recurrence in the cystectomy bed)&#xD;
&#xD;
          5. Completion of the initial phase (4-6 cycles) of 1st line metastatic treatment&#xD;
             (systemic therapy by chemotherapy and/or immunotherapy by immune check-point inhibitor&#xD;
             according to standard recommendations). Patients having started maintenance therapy&#xD;
             are eligible.&#xD;
&#xD;
          6. No disease progression after the initial phase of first-line metastatic systemic&#xD;
             therapy according to RECIST v1.1&#xD;
&#xD;
          7. No more than 3 residual metastatic lesions following the initial phase of first-line&#xD;
             metastatic systemic therapy:&#xD;
&#xD;
               1. The number of residual lesions is determined on the basis of the imaging modality&#xD;
                  for tumor response assessment performed after systemic treatment according to&#xD;
                  local habits (CT-scan or 18FDG PET-CT if performed):&#xD;
&#xD;
                  In case of response assessment by CT-scanner only: residual lesions are all&#xD;
                  remaining visible lesions&#xD;
&#xD;
                  In case of response assessment by additional 18FDG PET-CT: residual lesions are&#xD;
                  only the lesions with residual hyperfixation&#xD;
&#xD;
               2. Regarding distant lymph nodes metastases:&#xD;
&#xD;
             If evaluation is performed by CT-scanner only, residual lymph nodes are considered&#xD;
             pathological according to one or several criteria among:&#xD;
&#xD;
               -  Short axis ≥ 1cm&#xD;
&#xD;
               -  Central necrosis&#xD;
&#xD;
               -  Heterogeneous contrast enhancement&#xD;
&#xD;
             Residual para-aortic nodes involvement accounts for one lesion, even if several&#xD;
             para-aortic nodes are involved.&#xD;
&#xD;
             Other nodes: each involved node accounts for one lesion.&#xD;
&#xD;
          8. Residual metastases (if applicable) eligible for SBRT in terms of dose constraints to&#xD;
             the organs at risk, with no prior radiotherapy interfering with SBRT&#xD;
&#xD;
          9. 8 weeks or less between last cycle of the initial phase of systemic treatment and&#xD;
             randomization&#xD;
&#xD;
         10. No contraindication to pelvic radiotherapy&#xD;
&#xD;
         11. Signed informed consent&#xD;
&#xD;
         12. Patient able to participate and willing to give informed consent prior performance of&#xD;
             any study-related procedures and to comply with the study protocol&#xD;
&#xD;
         13. Patient affiliated to a Social Health Insurance in France.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Non-transitional cell histology (Squamous cell carcinoma, adenocarcinoma or&#xD;
             neuroendocrine carcinoma of the bladder)&#xD;
&#xD;
          2. Brain metastases before systemic treatment&#xD;
&#xD;
          3. Liver metastases before systemic treatment&#xD;
&#xD;
          4. Absence of target to be irradiated (i.e. previous cystectomy + no residual lesions&#xD;
             following systemic treatment + no pelvic or para-aortic nodes at metastatic&#xD;
             presentation)&#xD;
&#xD;
          5. Patient with relapse following definitive chemoradiation of the bladder&#xD;
&#xD;
          6. Local recurrence in the cystectomy bed following cystectomy&#xD;
&#xD;
          7. Previous pelvic irradiation&#xD;
&#xD;
          8. Prior radiotherapy near the residual metastatic lesions precluding ablative SBRT&#xD;
&#xD;
          9. Active inflammatory bowel disease&#xD;
&#xD;
         10. Contraindication to SBRT of a lesion due to organ dysfunction; in particular, patients&#xD;
             with lung lesions and documented or suspected interstitial lung disease should not be&#xD;
             included&#xD;
&#xD;
         11. History of scleroderma&#xD;
&#xD;
         12. Current or past history of second neoplasm diagnosed within the last 5 years (except&#xD;
             basocellular carcinoma and prostate cancer incidentally discovered during previous&#xD;
             cystoprostatectomy and pelvic lymph node dissection and with a good prognosis [T stage&#xD;
             &lt;pT3b and Gleason &lt;8 and pN- and post-operative PSA &lt;0.1 ng/mL])&#xD;
&#xD;
         13. Pregnancy or breast feeding or inadequate contraceptive measures&#xD;
&#xD;
         14. Known psychiatric or substance abuse disorders that would interfere with cooperation&#xD;
             with the requirements of the trial&#xD;
&#xD;
         15. Any psychological, familial, geographic or social situation, according to the judgment&#xD;
             of investigator, potentially preventing the provision of informed consent or&#xD;
             compliance to study procedure&#xD;
&#xD;
         16. Patient who has forfeited his/her freedom by administrative or legal award or who is&#xD;
             under legal protection (curatorship and guardianship, protection of justice)&#xD;
&#xD;
         17. Concurrent enrolment in another interventional therapeutic clinical study&#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_contact>
    <last_name>Jonathan KHALIFA</last_name>
    <phone>05 31 15 54 01</phone>
    <email>khalifa.jonathan@iuct-oncopole.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Clinique Claude Bernard</name>
      <address>
        <city>Albi</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Laurent VOTRON</last_name>
      <phone>05 63 77 77 56</phone>
      <email>votron@claude-bernard-albi.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Institut de Cancerologie de L'Ouest</name>
      <address>
        <city>Angers</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nathalie MESGOUEZ-NEBOUT</last_name>
      <phone>02 41 35 27 00</phone>
      <email>thalie.mesgouez-nebout@ico-unicancer.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>CHU Besançon</name>
      <address>
        <city>Besançon</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jihane BOUSTANI</last_name>
      <phone>03 70 63 23 23</phone>
      <email>jboustani@chu-besançon.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Institut Bergonie</name>
      <address>
        <city>Bordeaux</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Paul SARGOS</last_name>
      <phone>05 56 33 33 33</phone>
      <email>P.Sargos@bordeaux.unicancer.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Chu Morvan</name>
      <address>
        <city>Brest</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ulrike SCHICK</last_name>
      <email>ulrike.schick@chu-brest.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Clinique Pasteur-Lanroze</name>
      <address>
        <city>Brest</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Matthieu CHASSERAY</last_name>
      <phone>02 98 31 30 07</phone>
      <email>m.chasseray@oncologie-brest.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Centre Francois Baclesse</name>
      <address>
        <city>Caen</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Pierre-Emmanuel BRACHET</last_name>
      <phone>02 31 45 50 02</phone>
      <email>pe.brachet@baclesse.unicancer.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Centre Jean Perrin</name>
      <address>
        <city>Clermont-Ferrand</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jessica MIROIR</last_name>
      <phone>04 73 27 81 42</phone>
      <email>jessica.miroir@clermont.unicancer.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Institut Andrée Dutreix</name>
      <address>
        <city>Dunkerque</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Thomas MULLIEZ</last_name>
      <phone>03 28 51 96 30</phone>
      <email>thomasmulliez@hotmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Centre Oscar Lambret</name>
      <address>
        <city>Lille</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>David PASQUIER</last_name>
      <phone>03 20 29 51 44</phone>
      <email>d-pasquier@o-lambret.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Institut Paoli-Calmettes</name>
      <address>
        <city>Marseille</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Naji SALEM</last_name>
      <phone>04 91 22 36 37</phone>
      <email>salemn@ipc.unicancer.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Institut Curie</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gilles CREHANGE</last_name>
      <phone>01 72 38 94 45</phone>
      <email>gilles.crehange@curie.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Groupement de Radiothérapie et d'Oncologie des Pyrénées</name>
      <address>
        <city>Pau</city>
        <country>France</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Institut de Cancerologie de L'Ouest</name>
      <address>
        <city>Saint-Herblain</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Valentine GUIMAS</last_name>
      <phone>02 40 57 99 55</phone>
      <email>valentine.guimas@ico.unicancer.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>HIA Bégin</name>
      <address>
        <city>Saint-Mandé</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hugo PICCHI</last_name>
      <phone>01 86 93 75 20</phone>
      <email>picchi.hugo90@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Institut de Cancerologie Lucien Neuwirth</name>
      <address>
        <city>Saint-Priest-en-Jarez</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Nicolas MAGNE</last_name>
      <phone>04 77 91 74 25</phone>
      <email>nicolas.magne@icloire.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Institut Universitaire du Cancer Toulouse Oncopole</name>
      <address>
        <city>Toulouse</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jonathan KHALIFA</last_name>
      <phone>05 31 15 54 29</phone>
      <email>khalifa.jonathan@iuct-oncopole.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Institut Gustave Roussy</name>
      <address>
        <city>Villejuif</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Pierre BLANCHARD</last_name>
      <phone>01 42 11 44 13</phone>
      <email>pierre.blanchard@gustaveroussy.fr</email>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>June 9, 2020</study_first_submitted>
  <study_first_submitted_qc>June 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>August 2, 2023</last_update_submitted>
  <last_update_submitted_qc>August 2, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Urothelial bladder cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <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/NCT04428554
org study id: 19 URO 15
nct id: NCT04428554
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This is a phase II, multicenter, randomized open-label and comparative study designed to
      evaluate whether local consolidative radiotherapy plus standard of care improves overall
      survival as compared to standard of care in patients with limited metastatic urothelial
      bladder cancer and without progression following the initial phase of first-line systemic
      therapy.

      Each patient will be followed during 4 years from the date of randomization.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Survival
time frame: 4 years for each patient
measure: Progression Free Survival
time frame: 4 years for each patient
measure: Safety will be assessed by the toxicity grading of the National Cancer Institute (NCI-CTCAE v5)
time frame: 4 years for each patient
measure: Quality of life will be evaluated by the EORTC QLQ-C-30 questionnaire
time frame: 4 years for each patient
arm group label: Control arm
arm group type: No Intervention
description: Standard of care
arm group label: Experimental arm
arm group type: Experimental
intervention type: Radiation
intervention name: Experimental arm
description: Consolidative radiotherapy (pelvic irradiation and/or metastases irradiation) + standard of care +/- previous transurethral resection of bladder tumor
arm group label: Experimental arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jonathan KHALIFA
phone: 05 31 15 54 01
email: khalifa.jonathan@iuct-oncopole.fr
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
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status: Recruiting
contact: 
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status: Recruiting
contact: 
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status: Recruiting
contact: 
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status: Recruiting
contact: 
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status: Recruiting
contact: 
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status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Withdrawn
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Sponsor
mesh term: Urinary Bladder Neoplasms