<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/NCT02254915</url>
  </required_header>
  <id_info>
    <org_study_id>CLN-002-00</org_study_id>
    <nct_id>NCT02254915</nct_id>
  </id_info>
  <brief_title>SHTC - EUROPE-1 Synergo Hyperthermia-Chemotherapy by European Urologists' Research Operation Preserving Evolution Study I</brief_title>
  <acronym>SHTC-EUROPE-1</acronym>
  <official_title>A Multi-Centre, Randomised, Open-Label Active-Controlled Study Comparing Safety and Efficacy of Synergo Radiofrequency (RF)-Induced Hyperthermia-Chemotherapy With Mitomycin C (RITE) Versus Bacillus Calmette-Guérin (BCG) as First-Line Treatment of Non-Muscle Invasive Papillary Bladder Cancer (NMIBC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical Enterprises Europe B.V.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical Enterprises Europe B.V.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A multi-institutional, prospective, randomised, open-label, superiority, comparative,&#xD;
      active-controlled, phase 3 study. The study will compare Synergo RF-induced&#xD;
      hyperthermia-chemotherapy (SHTC) plus mitomycin C (MMC) to standard treatment of bacillus&#xD;
      Calmette-Guérin (BCG) therapy as first-line adjuvant treatment for intermediate and high-risk&#xD;
      NMIBC, and will evaluate recurrence and progression rate over two years of follow-up.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Shortages of the active comparator drug (BCG) on the market worldwide and a growing uncertainty&#xD;
    as to its future supply.&#xD;
  </why_stopped>
  <primary_completion_date type="Anticipated">January 2020</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>RFS time</measure>
    <time_frame>2 years</time_frame>
    <description>The recurrence-free survival time in patients with NMIBC following treatment with SHTC (investigational arm) compared to BCG (controlled arm).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival time</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recurrence free survival time by risk group</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Organ preservation rate</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival time</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease-specific survival time</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>2 years</time_frame>
    <description>Safety (rate of adverse events), as well as tolerability of SHTC compared to BCG in terms of the frequency, severity and nature of adverse events and the treatment received.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment discontinuation</measure>
    <time_frame>2 years</time_frame>
    <description>Proportion of treatment discontinuation of SHTC compared to BCG</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Urinary Bladder Neoplasms</condition>
  <condition>Urologic Neoplasms</condition>
  <condition>Urogenital Neoplasms</condition>
  <condition>Neoplasms</condition>
  <condition>Neoplasms by Site</condition>
  <condition>Urinary Bladder Diseases</condition>
  <condition>Urologic Diseases</condition>
  <arm_group>
    <arm_group_label>Synergo + MMC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Synergo radiofrequency (RF)-Induced hyperthermia-chemotherapy (SHTC) with mitomycin C (RITE) intravesical therapy as first-line adjuvant treatment for intermediate and high-risk NMIBC,</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Bacillus Calmette-Guérin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intravesical BCG therapy as first-line adjuvant treatment for intermediate and high-risk NMIBC,</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Synergo + MMC</intervention_name>
    <description>Synergo radiofrequency (RF)-Induced hyperthermia-chemotherapy with mitomycin C (RITE). Intravesical instillation of MMC utilizing the Synergo system.</description>
    <arm_group_label>Synergo + MMC</arm_group_label>
    <other_name>RITE</other_name>
    <other_name>SHTC</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bacillus Calmette-Guérin</intervention_name>
    <description>Intravesical instillation of BCG.</description>
    <arm_group_label>Bacillus Calmette-Guérin</arm_group_label>
    <other_name>BCG</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with primary intermediate or high-risk papillary NMIBC according to the EAU&#xD;
             Guidelines and intermediate and high-risk recurrences that have not received BCG&#xD;
             within the previous 2 years or chemotherapy treatment (apart from one early&#xD;
             instillation) within the previous year.&#xD;
&#xD;
          2. All clinical, intra-operative and pathological items for the EAU risk stratification&#xD;
             must be documented including a bladder map.&#xD;
&#xD;
          3. Patients must have undergone a re-resection (second TURB in accordance with the EAU&#xD;
             Guidelines) (i) if the initial TURB was incomplete (ii) if there was no muscle in the&#xD;
             specimen after the initial TURB (except in TaG1/LG tumours) (iii) in all T1 and all&#xD;
             G3/HG tumours TURB of T1 sites must include muscle. Re-resection must be negative in&#xD;
             patients diagnosed with T1 and/or G3/HG and/or multiple tumours in the initial TURB.&#xD;
&#xD;
          4. No UC in the upper tract, kidney and ureters. This should be confirmed by CT-IVU or&#xD;
             IVU performed at time of initial diagnosis in selected cases as recommended in latest&#xD;
             EAU guidelines published prior to screening.&#xD;
&#xD;
          5. No UC in the urethra, excluded by visual inspection during cystoscopy and, in&#xD;
             addition, in patients with (i) tumour of trigone (ii) tumour of bladder neck (iii)&#xD;
             abnormal prostatic urethra UC must be excluded by biopsy of the prostatic urethra in&#xD;
             all male patients or, in female patients, from the portion of the urethra adjacent to&#xD;
             the bladder neck, before study recruitment.&#xD;
&#xD;
          6. All patients must have urine cytology dated within the screening period prior to&#xD;
             randomisation.&#xD;
&#xD;
          7. Age ≥ 18 yrs&#xD;
&#xD;
          8. Normal kidneys and ureters.&#xD;
&#xD;
          9. Pre-treatment haematology and biochemistry values within acceptable limits:&#xD;
&#xD;
             (i) haemoglobin ≥ 10 g/dl (g/100 ml) (ii) platelets ≥ 150 x 109/L (103/mm3) (iii) WBC&#xD;
             ≥ 3.0 x 109/L (103/mm3) (iv) ANC ≥ 1.5 x 109/L (103/mm3, absolute neutrophil count)&#xD;
             (v) Serum creatinine, SGOT, SGPT, Alkaline phosphatase: &lt; 1.5 x UNL (upper normal&#xD;
             limit)&#xD;
&#xD;
         10. Negative pregnancy test for women of child-bearing potential&#xD;
&#xD;
         11. A life expectancy at least of the duration of the trial.&#xD;
&#xD;
         12. Unfit or unwilling to have a full or partial cystectomy.&#xD;
&#xD;
         13. Signed informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. UC involving the prostatic urethra&#xD;
&#xD;
          2. Non-UC tumour of the urinary tract&#xD;
&#xD;
          3. Upper tract and intramural tumours (e.g. in Ostium).&#xD;
&#xD;
          4. History of stage &gt; T1 UC.&#xD;
&#xD;
          5. CIS (suspected or present).&#xD;
&#xD;
          6. Known or suspected reduced bladder capacity. Patients will have a US estimation of&#xD;
             maximum bladder capacity or void spontaneously the maximum they can retain in their&#xD;
             bladder, and this will be used to determine urine volume. A minimum volume of 250 ml&#xD;
             is required.&#xD;
&#xD;
          7. Bleeding disorder&#xD;
&#xD;
          8. Macrohaematuria of ≥ 250 RBC's/uL or equivalent (e.g. &gt; &quot;+++&quot; erythrocytes in a&#xD;
             dipstick analysis).&#xD;
&#xD;
          9. Pregnant or lactating women.&#xD;
&#xD;
         10. Women of childbearing potential unwilling or unable to use adequate contraception if&#xD;
             sexually active.&#xD;
&#xD;
         11. More than a maintenance dose of oral corticosteroids (maintenance dose defined as the&#xD;
             same dose regimen over the past 6 months for a condition requiring continual&#xD;
             corticosteroid treatment) or patients with an immuno-compromised state for any reason.&#xD;
&#xD;
         12. More than low-dose Methotrexate (&gt;17.5 mg once a week).&#xD;
&#xD;
         13. Other malignancy within the past five years, except: non-melanomatous skin cancer&#xD;
             cured by excision, adequately treated carcinoma in situ of the cervix or ductal CIS&#xD;
             (DCIS)/lobular CIS (LCIS) of the breast or stable prostate cancer (under active&#xD;
             surveillance or hormone control) with a life expectancy of more than 5 years.&#xD;
&#xD;
         14. Any known allergy or adverse event that would prevent them from receiving a treatment&#xD;
             that they may be randomised to within the trial.&#xD;
&#xD;
         15. Known untreated strictural disease or bladder neck contracture or any other condition&#xD;
             that may prevent catheterisation with 21F catheter. Patients may undergo dilation or&#xD;
             urethral incision before entering the study.&#xD;
&#xD;
         16. Bladder diverticula with cumulative diameter &gt; 1cm&#xD;
&#xD;
         17. UTI at any time within 6 months preceding randomisation.&#xD;
&#xD;
         18. Significant urinary incontinence (spontaneous, requiring use of pads)&#xD;
&#xD;
         19. History of pelvic irradiation&#xD;
&#xD;
         20. Patients with implanted electronic devices (such as cardiac pacemakers) unless they&#xD;
             receive permission from their treating physician (e.g., cardiologist) and are&#xD;
             monitored by a treating physician during the treatment session.&#xD;
&#xD;
         21. Participation in another study which includes treatment that is liable to have an&#xD;
             effect on this 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_official>
    <last_name>Igal Ruvinsky, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Medical Enterprises Europe B.V.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Gerson Luedecke, Dr. med.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Universitätsklinikum Gießen und Marburg</affiliation>
  </overall_official>
  <link>
    <url>http://www.synergo-medical.com/#!ongoing-clinical-trials-en/cx81</url>
    <description>Medical Enterprises ongoing trials</description>
  </link>
  <verification_date>March 2015</verification_date>
  <study_first_submitted>September 30, 2014</study_first_submitted>
  <study_first_submitted_qc>September 30, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 2, 2014</study_first_posted>
  <last_update_submitted>March 31, 2015</last_update_submitted>
  <last_update_submitted_qc>March 31, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 1, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Synergo</keyword>
  <keyword>RITE</keyword>
  <keyword>SHTC</keyword>
  <keyword>Non Muscle Invasive Bladder Cancer</keyword>
  <keyword>NMIBC</keyword>
  <keyword>Superficial Bladder Cancer</keyword>
  <keyword>Urothelial Cell Cancer</keyword>
  <keyword>Transitional Cell Cancer</keyword>
  <keyword>Mitomycin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Urinary Bladder Neoplasms</mesh_term>
    <mesh_term>Neoplasms by Site</mesh_term>
    <mesh_term>Urogenital Neoplasms</mesh_term>
    <mesh_term>Urologic Neoplasms</mesh_term>
    <mesh_term>Urologic Diseases</mesh_term>
    <mesh_term>Urinary Bladder Diseases</mesh_term>
    <mesh_term>Hyperthermia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>BCG Vaccine</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/NCT02254915
org study id: CLN-002-00
nct id: NCT02254915
lead sponsor: 
has dmc: Yes
A multi-institutional, prospective, randomised, open-label, superiority, comparative,
      active-controlled, phase 3 study. The study will compare Synergo RF-induced
      hyperthermia-chemotherapy (SHTC) plus mitomycin C (MMC) to standard treatment of bacillus
      Calmette-Guérin (BCG) therapy as first-line adjuvant treatment for intermediate and high-risk
      NMIBC, and will evaluate recurrence and progression rate over two years of follow-up.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: RFS time
time frame: 2 years
description: The recurrence-free survival time in patients with NMIBC following treatment with SHTC (investigational arm) compared to BCG (controlled arm).
measure: Progression-free survival time
time frame: 2 years
measure: Recurrence free survival time by risk group
time frame: 2 years
measure: Organ preservation rate
time frame: 2 years
measure: Overall survival time
time frame: 2 years
measure: Disease-specific survival time
time frame: 2 years
measure: Adverse events
time frame: 2 years
description: Safety (rate of adverse events), as well as tolerability of SHTC compared to BCG in terms of the frequency, severity and nature of adverse events and the treatment received.
measure: Treatment discontinuation
time frame: 2 years
description: Proportion of treatment discontinuation of SHTC compared to BCG
arm group label: Synergo + MMC
arm group type: Experimental
description: Synergo radiofrequency (RF)-Induced hyperthermia-chemotherapy (SHTC) with mitomycin C (RITE) intravesical therapy as first-line adjuvant treatment for intermediate and high-risk NMIBC,
arm group label: Bacillus Calmette-Guérin
arm group type: Active Comparator
description: Intravesical BCG therapy as first-line adjuvant treatment for intermediate and high-risk NMIBC,
intervention type: Device
intervention name: Synergo + MMC
description: Synergo radiofrequency (RF)-Induced hyperthermia-chemotherapy with mitomycin C (RITE). Intravesical instillation of MMC utilizing the Synergo system.
arm group label: Synergo + MMC
other name: RITE
other name: SHTC
intervention type: Drug
intervention name: Bacillus Calmette-Guérin
description: Intravesical instillation of BCG.
arm group label: Bacillus Calmette-Guérin
other name: BCG
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Igal Ruvinsky, PhD
role: Study Director
affiliation: Medical Enterprises Europe B.V.
last name: Gerson Luedecke, Dr. med.
role: Principal Investigator
affiliation: Universitätsklinikum Gießen und Marburg
url: http://www.synergo-medical.com/#!ongoing-clinical-trials-en/cx81
description: Medical Enterprises ongoing trials
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Urinary Bladder Neoplasms
mesh term: Neoplasms by Site
mesh term: Urogenital Neoplasms
mesh term: Urologic Neoplasms
mesh term: Urologic Diseases
mesh term: Urinary Bladder Diseases
mesh term: Hyperthermia
mesh term: BCG Vaccine