<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/NCT02969083</url>
  </required_header>
  <id_info>
    <org_study_id>EudraCT 2016-004017-27</org_study_id>
    <nct_id>NCT02969083</nct_id>
  </id_info>
  <brief_title>Feasibility of Neo-adjuvant Versus Adjuvant Chemotherapy in Upper Tract Urothelial Carcinoma</brief_title>
  <acronym>URANUS</acronym>
  <official_title>Neo-adjuvant Versus Adjuvant Chemotherapy in Upper Tract Urothelial Carcinoma: A Feasibility Phase II Randomized Clinical Trial (&quot;URANUS&quot;)&quot;</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The European Uro-Oncology Group</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Centre for Human Drug Research, Netherlands</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>The European Uro-Oncology Group</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study is to explore feasibility of Upper Tract Urothelial Carcinoma (UTUC)&#xD;
      treatments based in real world data in various European countries. The study will allow to&#xD;
      gain insight in the true proportion of patients that fit to receive complete cisplatin-based&#xD;
      neo-adjuvant or adjuvant chemotherapy, and the proportion and clinical outcome of patients&#xD;
      with poor prognostic factors (PS and renal function) who receive only standard treatment&#xD;
      (Radical nephroureterectomy (RNU)). This comparison will be made using a uniform diagnostic&#xD;
      and treatment protocol.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There are no definitive treatment recommendations for patients diagnosed with UTUC. Radical&#xD;
      nephroureterectomy (RNU) has been considered the gold standard treatment for UTUC. However&#xD;
      due to the high recurrence rates reported, patients are often offered perioperative&#xD;
      chemotherapy provided that they have a good renal function and performance status. With&#xD;
      regard to the choice of chemotherapy treatment, there are also no clear recommendations since&#xD;
      there are no data from randomized studies. If perioperative chemotherapy is considered in&#xD;
      daily practice, gemcitabine/cisplatin regimen is often chosen and occasionally dd-MVAC.&#xD;
&#xD;
      The aim of this study is to explore feasibility of UTUC treatments based in real world data&#xD;
      in various European countries. Patients who fulfil good prognostic factors (inclusion&#xD;
      criteria for treatment randomization) will be allocated to neo-adjuvant (Arm B) or adjuvant&#xD;
      (Arm C) chemotherapy (receiving 3 cycles of gemcitabine/cisplatin or dose dense Methotrexate,&#xD;
      Vinblastine, Adriamycin, and Cisplatin (MVAC). Patients who don't fulfil criteria for&#xD;
      treatment randomization will undergo Radical nephroureterectomy (RNU) only (Arm A). Patients&#xD;
      will be followed up for 5 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 28, 2018</start_date>
  <completion_date type="Anticipated">October 2025</completion_date>
  <primary_completion_date type="Anticipated">October 2023</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>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of UTUC patients randomized to neo- or adjuvant chemotherapy that is actually able to start and finalize three courses of planned chemotherapy</measure>
    <time_frame>6 months</time_frame>
    <description>Percentage of patients randomised to adjuvant or neo-adjuvant treatment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease Free Survival (DFS)</measure>
    <time_frame>1-2 years</time_frame>
    <description>time from randomisation to local recurrence or distant metastasis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>1-2 years</time_frame>
    <description>time from randomisation to death for any cause different from urothelial carcinoma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cancer-Specific Survival (CSS)</measure>
    <time_frame>1-2 years</time_frame>
    <description>time from randomisation to death from urothelial carcinoma</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Upper Tract Urothelial Carcinoma</condition>
  <arm_group>
    <arm_group_label>Radical nephro-ureterectomy (RNU)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patients who dont fulfil inclusion criteria for chemotherapy treatment randomization (poor renal function: Glomerular Filtration Rate (GFR) &lt;55 ml/min or unfit for cisplatin-based chemotherapy)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Gemcitabine/Cisplatin plus RNU</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patients who fulfil inclusion criteria for cisplatinum-based chemotherapy (renal function: GRF &gt; or = 55 ml/min) receiving 3 cycles of Gemcitabine (1000 mg/m2) + Cisplatin (70 mg/m2) every 3 weeks before surgery</description>
  </arm_group>
  <arm_group>
    <arm_group_label>RNU plus Gemcitabine/Cisplatin</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patients who fulfil inclusion criteria for cisplatinum-based chemotherapy (renal function: GRF &gt; or = 55 ml/min) receiving 3 cycles of Gemcitabine (1000 mg/m2) + Cisplatin (70 mg/m2) every 3 weeks after surgery</description>
  </arm_group>
  <arm_group>
    <arm_group_label>M-VAC protocol plus RNU</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patients who fulfil inclusion criteria for cisplatinum-based chemotherapy (renal function: GRF &gt; or = 55 ml/min) receiving 3 cycles of MVAC every 2 weeks (Methotrexate (30 mg /m²) , Vinblastine (3 mg /m²) , Adriamycin (30 mg /m²) , and Cisplatin (70 mg /m²) before surgery</description>
  </arm_group>
  <arm_group>
    <arm_group_label>RNU plus M-VAC protocol</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patients who fulfil inclusion criteria for cisplatinum-based chemotherapy (renal function: GRF &gt; or = 55 ml/min) receiving 3 cycles of MVAC every 2 weeks (Methotrexate (30 mg /m²) , Vinblastine (3 mg /m²) , Adriamycin (30 mg /m²) , and Cisplatin (70 mg /m²) after surgery</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>RNU</intervention_name>
    <description>Radical surgical removal by open or laparoscopic access</description>
    <arm_group_label>Gemcitabine/Cisplatin plus RNU</arm_group_label>
    <arm_group_label>M-VAC protocol plus RNU</arm_group_label>
    <arm_group_label>RNU plus Gemcitabine/Cisplatin</arm_group_label>
    <arm_group_label>RNU plus M-VAC protocol</arm_group_label>
    <arm_group_label>Radical nephro-ureterectomy (RNU)</arm_group_label>
    <other_name>Radical nephro-ureterectomy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine/Cisplatin</intervention_name>
    <description>Gemcitabine (1000 mg/m²) day 1 and 8 and Cisplatin (70 mg/m²) day 1</description>
    <arm_group_label>Gemcitabine/Cisplatin plus RNU</arm_group_label>
    <arm_group_label>RNU plus Gemcitabine/Cisplatin</arm_group_label>
    <other_name>Gemcitabine plus Cisplatin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>M-VAC Protocol</intervention_name>
    <description>Methotrexate (30 mg /m²) and Vinblastine 3 (mg /m²) day 1; Adriamycin 30 mg /m² and Cisplatin 70 mg /m² in day2</description>
    <arm_group_label>M-VAC protocol plus RNU</arm_group_label>
    <arm_group_label>RNU plus M-VAC protocol</arm_group_label>
    <other_name>DD MVAC</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
          -  Age &gt; 18 years&#xD;
&#xD;
          -  Histological and radiological defined UTUC: Histologically-confirmed diagnosis of&#xD;
             predominantly urothelial carcinoma of the upper urinary tract Patients with UTUC&#xD;
             cT2-pT4 cN0-N1 M0 (TNM classification)&#xD;
&#xD;
          -  Women with negative serum pregnancy test within 14 days of first dose of study&#xD;
             treatment and agreement to use effective contraception&#xD;
&#xD;
          -  Patients without bladder cancer or with concomitant non muscle invasive bladder cancer&#xD;
&#xD;
          -  Adequate organ system function defined as follows: Hematologic: Absolute neutrophil&#xD;
             count (ANC) 1.5 X 109/L; Haemoglobin 5.6 mmol/L (9.02g/dL); Platelets 100 X 109/L;&#xD;
             Prothrombin time (PT) or international normalized ratio (INR)b 1.2 X ULN; Activated&#xD;
             partial thromboplastin time (aPTT)1.2 X Upper limit of normal (ULN). Hepatic: Total&#xD;
             bilirubin 1.5 X ULN; Alanine amino transferase (ALT) and Aspartate aminotransferase&#xD;
             (AST) 2.5 X ULN. Renal: GRF &lt;or&gt; 55 ml/min: Electrolytes: potassium and calcium:&#xD;
             within normal limits.&#xD;
&#xD;
          -  CT scan of the chest, abdomen and pelvis and Bone scan without evidence of distant&#xD;
             metastasis&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Histology of pure adenocarcinoma, pure squamous cell carcinoma, sarcomatoid or&#xD;
             predominant small cell carcinoma.&#xD;
&#xD;
          -  History of cardiovascular conditions within the past 6 months.&#xD;
&#xD;
          -  Incidentally found asymptomatic pulmonary embolism (PE) or recent deep vein thrombosis&#xD;
             (DVT) is not an exclusion criteria but requires anticoagulation treatment.&#xD;
&#xD;
          -  Any major contraindication to a surgical procedure.&#xD;
&#xD;
          -  Any serious and/or unstable pre-existing medical, psychiatric, or other condition that&#xD;
             could interfere with subject's safety, provision of informed consent, or compliance to&#xD;
             study procedures.&#xD;
&#xD;
          -  Active infection contraindicating chemotherapy&#xD;
&#xD;
          -  Other active neoplasms. Patients with in situ cervical carcinoma, non-melanoma skin&#xD;
             cancer or prostate cancer T1 Gleason &lt;7, Prostate specific antigen (PSA) &lt;10. Patients&#xD;
             with past medical history of cancer can be included if diagnosed at least 4 years ago.&#xD;
&#xD;
          -  Concomitant muscle invasive bladder cancer&#xD;
&#xD;
          -  Patients who have been or still are on methotrexate treatment.&#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>Susanne Osanto, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Leiden University Medical Centre</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Cristina Alvarez, MSc, PhD</last_name>
    <phone>+31(0)715264109</phone>
    <email>m.c.alvarez@lumc.nl</email>
  </overall_contact>
  <location>
    <facility>
      <name>Radboud University Medical Centre</name>
      <address>
        <city>Nijmegen</city>
        <state>Gelderland</state>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>T Van der Heijden</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Leiden University Medical Centre</name>
      <address>
        <city>Leiden</city>
        <state>South Holland</state>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>S Osanto</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Alrijne Ziekenhuis</name>
      <address>
        <city>Leiderdorp</city>
        <state>South-Holland</state>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>C Goossens-Laan</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Canisius Wilhelmina Ziekenhuis</name>
      <address>
        <city>Nijmegen</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>R Somford</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Haukeland University Hospital</name>
      <address>
        <city>Bergen</city>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>C Beisland</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Complejo Hospitalario Universitario A Coruña</name>
      <address>
        <city>A Coruña</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Dr. Molina</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario German Trias i Pujol</name>
      <address>
        <city>Badalona</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dr. Alves</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Fundacion Puigvert</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>J Palou</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Clinico de Barcelona</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Dr. Ribal</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital San Pau</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>P Maroto</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Dr. Gonzalez</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Basurto</name>
      <address>
        <city>Bilbao</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Dr. Anton</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari de Girona Doctor Josep Trueta</name>
      <address>
        <city>Gerona</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dr. Comet</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Clínico San Cecilio</name>
      <address>
        <city>Granada</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dr. Arrabal</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital de Jerez</name>
      <address>
        <city>Jerez De La Frontera</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Dr. Amores</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Complex Insular-Materno Infantil</name>
      <address>
        <city>Las Palmas</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Dr. Gómez de Liaño</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Clinica Universitaria de Navarra</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dr. Villacampa</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Fundacion Jimenez Diaz</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Dr. Buendia</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital ramón y Cajal</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dr. Burgos</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario La Paz</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dr. Alvarez-Maestro</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Clinico Universitario Virgen de la Arrixaca</name>
      <address>
        <city>Murcia</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dr. Lopez-Cubillana</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario Morales Meseguer</name>
      <address>
        <city>Murcia</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Dr. Fernandez Aparicio</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Complejo Hospitalario de Navarra</name>
      <address>
        <city>Pamplona</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dr. Montesino</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Parc Taulí</name>
      <address>
        <city>Sabadell</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dr. Gallardo</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Salamanca</name>
      <address>
        <city>Salamanca</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dr. Gomez Veiga</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Marques de Valdecilla</name>
      <address>
        <city>Santander</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dr. Campos Juanatey</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Virgen del Rocio</name>
      <address>
        <city>Sevilla</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dr. Osman</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Fundacion Instituto Valenciano de Oncologia</name>
      <address>
        <city>Valencia</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Dr. Climent</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Clinico Universitario Lozano Blesa</name>
      <address>
        <city>Zaragoza</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Dr. Rioja</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Netherlands</country>
    <country>Norway</country>
    <country>Spain</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>November 11, 2016</study_first_submitted>
  <study_first_submitted_qc>November 17, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2016</study_first_posted>
  <last_update_submitted>March 7, 2023</last_update_submitted>
  <last_update_submitted_qc>March 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>UTUC</keyword>
  <keyword>Upper Tract Urothelial Carcinoma</keyword>
  <keyword>Neoadjuvant chemotherapy</keyword>
  <keyword>Adjuvant chemotherapy</keyword>
  <keyword>Radical nephroureterectomy</keyword>
  <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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cisplatin</mesh_term>
    <mesh_term>Gemcitabine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>The results obtained in this study will be disseminated and published</ipd_description>
  </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/NCT02969083
org study id: EudraCT 2016-004017-27
nct id: NCT02969083
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The aim of this study is to explore feasibility of Upper Tract Urothelial Carcinoma (UTUC)
      treatments based in real world data in various European countries. The study will allow to
      gain insight in the true proportion of patients that fit to receive complete cisplatin-based
      neo-adjuvant or adjuvant chemotherapy, and the proportion and clinical outcome of patients
      with poor prognostic factors (PS and renal function) who receive only standard treatment
      (Radical nephroureterectomy (RNU)). This comparison will be made using a uniform diagnostic
      and treatment protocol.
There are no definitive treatment recommendations for patients diagnosed with UTUC. Radical
      nephroureterectomy (RNU) has been considered the gold standard treatment for UTUC. However
      due to the high recurrence rates reported, patients are often offered perioperative
      chemotherapy provided that they have a good renal function and performance status. With
      regard to the choice of chemotherapy treatment, there are also no clear recommendations since
      there are no data from randomized studies. If perioperative chemotherapy is considered in
      daily practice, gemcitabine/cisplatin regimen is often chosen and occasionally dd-MVAC.

      The aim of this study is to explore feasibility of UTUC treatments based in real world data
      in various European countries. Patients who fulfil good prognostic factors (inclusion
      criteria for treatment randomization) will be allocated to neo-adjuvant (Arm B) or adjuvant
      (Arm C) chemotherapy (receiving 3 cycles of gemcitabine/cisplatin or dose dense Methotrexate,
      Vinblastine, Adriamycin, and Cisplatin (MVAC). Patients who don't fulfil criteria for
      treatment randomization will undergo Radical nephroureterectomy (RNU) only (Arm A). Patients
      will be followed up for 5 years.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: Proportion of UTUC patients randomized to neo- or adjuvant chemotherapy that is actually able to start and finalize three courses of planned chemotherapy
time frame: 6 months
description: Percentage of patients randomised to adjuvant or neo-adjuvant treatment
measure: Disease Free Survival (DFS)
time frame: 1-2 years
description: time from randomisation to local recurrence or distant metastasis
measure: Overall Survival (OS)
time frame: 1-2 years
description: time from randomisation to death for any cause different from urothelial carcinoma
measure: Cancer-Specific Survival (CSS)
time frame: 1-2 years
description: time from randomisation to death from urothelial carcinoma
arm group label: Radical nephro-ureterectomy (RNU)
arm group type: Other
description: Patients who dont fulfil inclusion criteria for chemotherapy treatment randomization (poor renal function: Glomerular Filtration Rate (GFR) <55 ml/min or unfit for cisplatin-based chemotherapy)
arm group label: Gemcitabine/Cisplatin plus RNU
arm group type: Other
description: Patients who fulfil inclusion criteria for cisplatinum-based chemotherapy (renal function: GRF > or = 55 ml/min) receiving 3 cycles of Gemcitabine (1000 mg/m2) + Cisplatin (70 mg/m2) every 3 weeks before surgery
arm group label: RNU plus Gemcitabine/Cisplatin
arm group type: Other
description: Patients who fulfil inclusion criteria for cisplatinum-based chemotherapy (renal function: GRF > or = 55 ml/min) receiving 3 cycles of Gemcitabine (1000 mg/m2) + Cisplatin (70 mg/m2) every 3 weeks after surgery
arm group label: M-VAC protocol plus RNU
arm group type: Other
description: Patients who fulfil inclusion criteria for cisplatinum-based chemotherapy (renal function: GRF > or = 55 ml/min) receiving 3 cycles of MVAC every 2 weeks (Methotrexate (30 mg /m²) , Vinblastine (3 mg /m²) , Adriamycin (30 mg /m²) , and Cisplatin (70 mg /m²) before surgery
arm group label: RNU plus M-VAC protocol
arm group type: Other
description: Patients who fulfil inclusion criteria for cisplatinum-based chemotherapy (renal function: GRF > or = 55 ml/min) receiving 3 cycles of MVAC every 2 weeks (Methotrexate (30 mg /m²) , Vinblastine (3 mg /m²) , Adriamycin (30 mg /m²) , and Cisplatin (70 mg /m²) after surgery
intervention type: Procedure
intervention name: RNU
description: Radical surgical removal by open or laparoscopic access
arm group label: Gemcitabine/Cisplatin plus RNU
arm group label: M-VAC protocol plus RNU
arm group label: RNU plus Gemcitabine/Cisplatin
arm group label: RNU plus M-VAC protocol
arm group label: Radical nephro-ureterectomy (RNU)
other name: Radical nephro-ureterectomy
intervention type: Drug
intervention name: Gemcitabine/Cisplatin
description: Gemcitabine (1000 mg/m²) day 1 and 8 and Cisplatin (70 mg/m²) day 1
arm group label: Gemcitabine/Cisplatin plus RNU
arm group label: RNU plus Gemcitabine/Cisplatin
other name: Gemcitabine plus Cisplatin
intervention type: Drug
intervention name: M-VAC Protocol
description: Methotrexate (30 mg /m²) and Vinblastine 3 (mg /m²) day 1; Adriamycin 30 mg /m² and Cisplatin 70 mg /m² in day2
arm group label: M-VAC protocol plus RNU
arm group label: RNU plus M-VAC protocol
other name: DD MVAC
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Susanne Osanto, MD, PhD
role: Principal Investigator
affiliation: Leiden University Medical Centre
last name: Cristina Alvarez, MSc, PhD
phone: +31(0)715264109
email: m.c.alvarez@lumc.nl
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country: Netherlands
country: Norway
country: Spain
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Transitional Cell
mesh term: Cisplatin
mesh term: Gemcitabine
sharing ipd: No
ipd description: The results obtained in this study will be disseminated and published