<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/NCT01726374</url>
  </required_header>
  <id_info>
    <org_study_id>ICR-CTSU/2008/10019</org_study_id>
    <secondary_id>ISRCTN37875250</secondary_id>
    <secondary_id>2008-006295-29</secondary_id>
    <secondary_id>09/H1102/86</secondary_id>
    <secondary_id>CRUK/09/011</secondary_id>
    <nct_id>NCT01726374</nct_id>
  </id_info>
  <brief_title>Trial of 1 Cycle of Adjuvant BEP Chemotherapy in High Risk, Stage 1 Non-seminomatous Germ Cell Testis Tumours</brief_title>
  <acronym>111</acronym>
  <official_title>A Single Group Trial Evaluating One Cycle of Adjuvant BEP Chemotherapy in High Risk, Stage 1 Non-seminomatous Germ Cell Tumours of the Testis (NSGCTT)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institute of Cancer Research, United Kingdom</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University Hospital Birmingham NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Cancer Research UK</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Institute of Cancer Research, United Kingdom</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      High-risk stage 1 NSGCTTs are curable with careful surveillance followed by 3 cycles of BEP&#xD;
      (bleomycin, etoposide, cisplatin with 500mg/m2 of etoposide per cycle) chemotherapy for the&#xD;
      40-50% of cases experiencing recurrence. Alternatively, adjuvant chemotherapy with 2 cycles&#xD;
      of BEP(at a lower dose than that used for advanced disease - etoposide 360mg/m2) for these&#xD;
      patients achieves the same outcome and avoids intensive surveillance, but delivers 33% more&#xD;
      chemotherapy cycles on a population basis.&#xD;
&#xD;
      If a single cycle of BEP at the dose used in advanced disease had a similar high rate of&#xD;
      relapse-free survival (cure) to that seen with two lower dose cycles, this would reduce the&#xD;
      overall burden of chemotherapy and healthcare resource usage and would be likely to lead to a&#xD;
      change in practice globally.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">February 2010</start_date>
  <completion_date type="Anticipated">August 2020</completion_date>
  <primary_completion_date type="Actual">August 2016</primary_completion_date>
  <phase>Phase 3</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>Recurrence</measure>
    <time_frame>2 years</time_frame>
    <description>To demonstrate that one cycle of adjuvant BEP(500) reduces 2 year recurrence rate to less than 5%</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Immediate and delayed toxicity including long-term permanent infertility (&gt;2 years)</measure>
    <time_frame>0 - &gt; 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relapse free survival</measure>
    <time_frame>Patients followed up for 5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Patients followed up for 5 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">246</enrollment>
  <condition>Stage I Testicular Non-Seminomatous Germ Cell Tumor</condition>
  <arm_group>
    <arm_group_label>One cycle adjuvant BEP(500)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Etoposide 165 mg/m2 IV infusion - days 1, 2, 3 Cisplatin 50 mg/m2 IV infusion - days 1, 2 Bleomycin 30,000 IU IV infusion - days 1 (or 2), 8, 15</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BEP(500)</intervention_name>
    <description>One cycle of BEP(500):&#xD;
Etoposide 165 mg/m2 IV infusion - days 1, 2, 3 Cisplatin 50 mg/m2 IV infusion - days 1, 2 Bleomycin 30,000 IU IV infusion - days 1 (or 2), 8, 15</description>
    <arm_group_label>One cycle adjuvant BEP(500)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically proven non-seminomatous germ cell tumour of combined GCT (NSGCT +&#xD;
             seminoma)of the testis&#xD;
&#xD;
          -  Histologically proven vascular invasion of the primary tumour into the testicular&#xD;
             veins or lymphatics&#xD;
&#xD;
          -  Clinical stage 1 patients (normal AFP and HCG, or optimum marker decline approaching&#xD;
             normal levels after orchidectomy AND no evidence of metastases on CT of chest, abdomen&#xD;
             and pelvis)&#xD;
&#xD;
          -  Men aged 16 years or over&#xD;
&#xD;
          -  Creatinine clearance &gt; 50 ml/min&#xD;
&#xD;
          -  No previous chemotherapy&#xD;
&#xD;
          -  WBC &gt; 1.5 x 10^9/l and platelets 100 x 10^9/l&#xD;
&#xD;
          -  Fit to receive chemotherapy&#xD;
&#xD;
          -  Able to start BEP(500) chemotherapy as part of 111 study within 6* weeks of&#xD;
             orchidectomy&#xD;
&#xD;
          -  Written informed consent *If there are unavoidable delays this timescale can be&#xD;
             extended to 8 weeks&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  All patients with pure seminoma&#xD;
&#xD;
          -  All patients with non-seminoma or combined NSGCT + seminoma &gt; stage 1&#xD;
&#xD;
          -  All patients with no vascular invasion&#xD;
&#xD;
          -  Previous chemotherapy&#xD;
&#xD;
          -  Patients with second malignancy except contralateral TIN and contralateral germ cell&#xD;
             tumour treated by orchidectomy and subsequent surveillance of more than 3 years&#xD;
&#xD;
          -  Co-morbidity precluding the safe administration of BEP(500) chemotherapy&#xD;
&#xD;
          -  Patients with renal function impairment (bilirubin &gt;1.25 x ULN and/or AST &gt;2 x ULN)&#xD;
&#xD;
          -  Patients with pre-existing neuropathy&#xD;
&#xD;
          -  Patients with pulmonary fibrosis&#xD;
&#xD;
          -  Patients with serious illness or medical conditions incompatible with the protocol&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Professor Michael Cullen</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Birmingham NHS Foundation Trust</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Guy's Hospital</name>
      <address>
        <city>London</city>
        <state>England</state>
        <zip>SE1 9RT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northampton General Hospital NHS Trust</name>
      <address>
        <city>Northampton</city>
        <state>England</state>
        <zip>NN6 8BJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Velindre Cancer Center at Velindre Hospital</name>
      <address>
        <city>Cardiff</city>
        <state>Wales</state>
        <zip>CF14 2TL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aberdeen Royal Infirmary</name>
      <address>
        <city>Aberdeen</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ysbyty Gwynedd</name>
      <address>
        <city>Bangor</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen Elizabeth Hospital</name>
      <address>
        <city>Birmingham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Sussex County Hospital</name>
      <address>
        <city>Brighton</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bristol Haematology and Oncology Centre</name>
      <address>
        <city>Bristol</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen's Hospital</name>
      <address>
        <city>Burton-on-Trent</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Addenbrooke's Hospital</name>
      <address>
        <city>Cambridge</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cheltenham General Hospital</name>
      <address>
        <city>Cheltenham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gloucestershire Royal Hospital</name>
      <address>
        <city>Cheltenham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals Coventry and Warwickshire NHS Trust</name>
      <address>
        <city>Coventry</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Derby Hospital</name>
      <address>
        <city>Derby</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Western General Hospital</name>
      <address>
        <city>Edinburgh</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Devon and Exeter Hospital</name>
      <address>
        <city>Exeter</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beatson West of Scotland Cancer Centre</name>
      <address>
        <city>Glasgow</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Surrey County Hospital</name>
      <address>
        <city>Guildford</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Castle Hill Hospital</name>
      <address>
        <city>Hull</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ipswich Hospital</name>
      <address>
        <city>Ipswich</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St James's University Hospital</name>
      <address>
        <city>Leeds</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Leicester Royal Infirmary</name>
      <address>
        <city>Leicester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lincoln County Hospital</name>
      <address>
        <city>Lincoln</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clatterbridge Centre for Oncology</name>
      <address>
        <city>Liverpool</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Liverpool University Hospital</name>
      <address>
        <city>Liverpool</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Bartholomew's Hospital</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University College Hospital</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maidstone Hospital</name>
      <address>
        <city>Maidstone</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>James Cook University Hospital</name>
      <address>
        <city>Middlesbrough</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Norfolk and Norwich University Hospital</name>
      <address>
        <city>Norwich</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nottingham City Hospital</name>
      <address>
        <city>Nottingham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Churchill Hospital</name>
      <address>
        <city>Oxford</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Weston Park Hospital</name>
      <address>
        <city>Sheffield</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southampton General Hospital</name>
      <address>
        <city>Southampton</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Marsden Hospital</name>
      <address>
        <city>Sutton</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <results_reference>
    <citation>Cullen M, Huddart R, Joffe J, Gardiner D, Maynard L, Hutton P, Mazhar D, Shamash J, Wheater M, White J, Goubar A, Porta N, Witts S, Lewis R, Hall E; 111 Trial Management Group. The 111 Study: A Single-arm, Phase 3 Trial Evaluating One Cycle of Bleomycin, Etoposide, and Cisplatin as Adjuvant Chemotherapy in High-risk, Stage 1 Nonseminomatous or Combined Germ Cell Tumours of the Testis. Eur Urol. 2020 Mar;77(3):344-351. doi: 10.1016/j.eururo.2019.11.022. Epub 2020 Jan 1.</citation>
    <PMID>31901440</PMID>
  </results_reference>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>November 9, 2012</study_first_submitted>
  <study_first_submitted_qc>November 9, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 14, 2012</study_first_posted>
  <last_update_submitted>April 30, 2020</last_update_submitted>
  <last_update_submitted_qc>April 30, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 4, 2020</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>Neoplasms, Germ Cell and Embryonal</mesh_term>
    <mesh_term>Testicular 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/NCT01726374
org study id: ICR-CTSU/2008/10019
secondary id: ISRCTN37875250
secondary id: 2008-006295-29
secondary id: 09/H1102/86
secondary id: CRUK/09/011
nct id: NCT01726374
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
High-risk stage 1 NSGCTTs are curable with careful surveillance followed by 3 cycles of BEP
      (bleomycin, etoposide, cisplatin with 500mg/m2 of etoposide per cycle) chemotherapy for the
      40-50% of cases experiencing recurrence. Alternatively, adjuvant chemotherapy with 2 cycles
      of BEP(at a lower dose than that used for advanced disease - etoposide 360mg/m2) for these
      patients achieves the same outcome and avoids intensive surveillance, but delivers 33% more
      chemotherapy cycles on a population basis.

      If a single cycle of BEP at the dose used in advanced disease had a similar high rate of
      relapse-free survival (cure) to that seen with two lower dose cycles, this would reduce the
      overall burden of chemotherapy and healthcare resource usage and would be likely to lead to a
      change in practice globally.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Recurrence
time frame: 2 years
description: To demonstrate that one cycle of adjuvant BEP(500) reduces 2 year recurrence rate to less than 5%
measure: Immediate and delayed toxicity including long-term permanent infertility (>2 years)
time frame: 0 - > 2 years
measure: Relapse free survival
time frame: Patients followed up for 5 years
measure: Overall survival
time frame: Patients followed up for 5 years
arm group label: One cycle adjuvant BEP(500)
arm group type: Experimental
description: Etoposide 165 mg/m2 IV infusion - days 1, 2, 3 Cisplatin 50 mg/m2 IV infusion - days 1, 2 Bleomycin 30,000 IU IV infusion - days 1 (or 2), 8, 15
intervention type: Drug
intervention name: BEP(500)
description: One cycle of BEP(500):
Etoposide 165 mg/m2 IV infusion - days 1, 2, 3 Cisplatin 50 mg/m2 IV infusion - days 1, 2 Bleomycin 30,000 IU IV infusion - days 1 (or 2), 8, 15
arm group label: One cycle adjuvant BEP(500)
criteria: 
gender: Male
minimum age: 16 Years
maximum age: N/A
healthy volunteers: No
last name: Professor Michael Cullen
role: Principal Investigator
affiliation: University Hospital Birmingham NHS Foundation Trust
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country: United Kingdom
citation: Cullen M, Huddart R, Joffe J, Gardiner D, Maynard L, Hutton P, Mazhar D, Shamash J, Wheater M, White J, Goubar A, Porta N, Witts S, Lewis R, Hall E; 111 Trial Management Group. The 111 Study: A Single-arm, Phase 3 Trial Evaluating One Cycle of Bleomycin, Etoposide, and Cisplatin as Adjuvant Chemotherapy in High-risk, Stage 1 Nonseminomatous or Combined Germ Cell Tumours of the Testis. Eur Urol. 2020 Mar;77(3):344-351. doi: 10.1016/j.eururo.2019.11.022. Epub 2020 Jan 1.
PMID: 31901440
responsible party type: Sponsor
mesh term: Neoplasms, Germ Cell and Embryonal
mesh term: Testicular Neoplasms