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SHTC - EUROPE-1 Synergo Hyperthermia-Chemotherapy by European Urologists' Research Operation Preserving Evolution Study I (SHTC-EUROPE-1)

Primary Purpose

Urinary Bladder Neoplasms, Urologic Neoplasms, Urogenital Neoplasms

Status
Withdrawn
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Synergo + MMC
Bacillus Calmette-Guérin
Sponsored by
Medical Enterprises Europe B.V.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Urinary Bladder Neoplasms focused on measuring Synergo, RITE, SHTC, Non Muscle Invasive Bladder Cancer, NMIBC, Superficial Bladder Cancer, Urothelial Cell Cancer, Transitional Cell Cancer, Mitomycin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Patients with primary intermediate or high-risk papillary NMIBC according to the EAU Guidelines and intermediate and high-risk recurrences that have not received BCG within the previous 2 years or chemotherapy treatment (apart from one early instillation) within the previous year.
  2. All clinical, intra-operative and pathological items for the EAU risk stratification must be documented including a bladder map.
  3. Patients must have undergone a re-resection (second TURB in accordance with the EAU Guidelines) (i) if the initial TURB was incomplete (ii) if there was no muscle in the specimen after the initial TURB (except in TaG1/LG tumours) (iii) in all T1 and all G3/HG tumours TURB of T1 sites must include muscle. Re-resection must be negative in patients diagnosed with T1 and/or G3/HG and/or multiple tumours in the initial TURB.
  4. No UC in the upper tract, kidney and ureters. This should be confirmed by CT-IVU or IVU performed at time of initial diagnosis in selected cases as recommended in latest EAU guidelines published prior to screening.
  5. No UC in the urethra, excluded by visual inspection during cystoscopy and, in addition, in patients with (i) tumour of trigone (ii) tumour of bladder neck (iii) abnormal prostatic urethra UC must be excluded by biopsy of the prostatic urethra in all male patients or, in female patients, from the portion of the urethra adjacent to the bladder neck, before study recruitment.
  6. All patients must have urine cytology dated within the screening period prior to randomisation.
  7. Age ≥ 18 yrs
  8. Normal kidneys and ureters.
  9. Pre-treatment haematology and biochemistry values within acceptable limits:

    (i) haemoglobin ≥ 10 g/dl (g/100 ml) (ii) platelets ≥ 150 x 109/L (103/mm3) (iii) WBC ≥ 3.0 x 109/L (103/mm3) (iv) ANC ≥ 1.5 x 109/L (103/mm3, absolute neutrophil count) (v) Serum creatinine, SGOT, SGPT, Alkaline phosphatase: < 1.5 x UNL (upper normal limit)

  10. Negative pregnancy test for women of child-bearing potential
  11. A life expectancy at least of the duration of the trial.
  12. Unfit or unwilling to have a full or partial cystectomy.
  13. Signed informed consent.

Exclusion Criteria:

  1. UC involving the prostatic urethra
  2. Non-UC tumour of the urinary tract
  3. Upper tract and intramural tumours (e.g. in Ostium).
  4. History of stage > T1 UC.
  5. CIS (suspected or present).
  6. Known or suspected reduced bladder capacity. Patients will have a US estimation of maximum bladder capacity or void spontaneously the maximum they can retain in their bladder, and this will be used to determine urine volume. A minimum volume of 250 ml is required.
  7. Bleeding disorder
  8. Macrohaematuria of ≥ 250 RBC's/uL or equivalent (e.g. > "+++" erythrocytes in a dipstick analysis).
  9. Pregnant or lactating women.
  10. Women of childbearing potential unwilling or unable to use adequate contraception if sexually active.
  11. More than a maintenance dose of oral corticosteroids (maintenance dose defined as the same dose regimen over the past 6 months for a condition requiring continual corticosteroid treatment) or patients with an immuno-compromised state for any reason.
  12. More than low-dose Methotrexate (>17.5 mg once a week).
  13. Other malignancy within the past five years, except: non-melanomatous skin cancer cured by excision, adequately treated carcinoma in situ of the cervix or ductal CIS (DCIS)/lobular CIS (LCIS) of the breast or stable prostate cancer (under active surveillance or hormone control) with a life expectancy of more than 5 years.
  14. Any known allergy or adverse event that would prevent them from receiving a treatment that they may be randomised to within the trial.
  15. Known untreated strictural disease or bladder neck contracture or any other condition that may prevent catheterisation with 21F catheter. Patients may undergo dilation or urethral incision before entering the study.
  16. Bladder diverticula with cumulative diameter > 1cm
  17. UTI at any time within 6 months preceding randomisation.
  18. Significant urinary incontinence (spontaneous, requiring use of pads)
  19. History of pelvic irradiation
  20. Patients with implanted electronic devices (such as cardiac pacemakers) unless they receive permission from their treating physician (e.g., cardiologist) and are monitored by a treating physician during the treatment session.
  21. Participation in another study which includes treatment that is liable to have an effect on this study.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Synergo + MMC

    Bacillus Calmette-Guérin

    Arm 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,

    Intravesical BCG therapy as first-line adjuvant treatment for intermediate and high-risk NMIBC,

    Outcomes

    Primary Outcome Measures

    RFS time
    The recurrence-free survival time in patients with NMIBC following treatment with SHTC (investigational arm) compared to BCG (controlled arm).

    Secondary Outcome Measures

    Progression-free survival time
    Recurrence free survival time by risk group
    Organ preservation rate
    Overall survival time
    Disease-specific survival time
    Adverse events
    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.
    Treatment discontinuation
    Proportion of treatment discontinuation of SHTC compared to BCG

    Full Information

    First Posted
    September 30, 2014
    Last Updated
    March 31, 2015
    Sponsor
    Medical Enterprises Europe B.V.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02254915
    Brief Title
    SHTC - EUROPE-1 Synergo Hyperthermia-Chemotherapy by European Urologists' Research Operation Preserving Evolution Study I
    Acronym
    SHTC-EUROPE-1
    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)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2015
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Shortages of the active comparator drug (BCG) on the market worldwide and a growing uncertainty as to its future supply.
    Study Start Date
    undefined (undefined)
    Primary Completion Date
    January 2020 (Anticipated)
    Study Completion Date
    undefined (undefined)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Medical Enterprises Europe B.V.

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Urinary Bladder Neoplasms, Urologic Neoplasms, Urogenital Neoplasms, Neoplasms, Neoplasms by Site, Urinary Bladder Diseases, Urologic Diseases
    Keywords
    Synergo, RITE, SHTC, Non Muscle Invasive Bladder Cancer, NMIBC, Superficial Bladder Cancer, Urothelial Cell Cancer, Transitional Cell Cancer, Mitomycin

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Synergo + MMC
    Arm Type
    Experimental
    Arm 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 Title
    Bacillus Calmette-Guérin
    Arm Type
    Active Comparator
    Arm Description
    Intravesical BCG therapy as first-line adjuvant treatment for intermediate and high-risk NMIBC,
    Intervention Type
    Device
    Intervention Name(s)
    Synergo + MMC
    Other Intervention Name(s)
    RITE, SHTC
    Intervention Description
    Synergo radiofrequency (RF)-Induced hyperthermia-chemotherapy with mitomycin C (RITE). Intravesical instillation of MMC utilizing the Synergo system.
    Intervention Type
    Drug
    Intervention Name(s)
    Bacillus Calmette-Guérin
    Other Intervention Name(s)
    BCG
    Intervention Description
    Intravesical instillation of BCG.
    Primary Outcome Measure Information:
    Title
    RFS time
    Description
    The recurrence-free survival time in patients with NMIBC following treatment with SHTC (investigational arm) compared to BCG (controlled arm).
    Time Frame
    2 years
    Secondary Outcome Measure Information:
    Title
    Progression-free survival time
    Time Frame
    2 years
    Title
    Recurrence free survival time by risk group
    Time Frame
    2 years
    Title
    Organ preservation rate
    Time Frame
    2 years
    Title
    Overall survival time
    Time Frame
    2 years
    Title
    Disease-specific survival time
    Time Frame
    2 years
    Title
    Adverse events
    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.
    Time Frame
    2 years
    Title
    Treatment discontinuation
    Description
    Proportion of treatment discontinuation of SHTC compared to BCG
    Time Frame
    2 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Patients with primary intermediate or high-risk papillary NMIBC according to the EAU Guidelines and intermediate and high-risk recurrences that have not received BCG within the previous 2 years or chemotherapy treatment (apart from one early instillation) within the previous year. All clinical, intra-operative and pathological items for the EAU risk stratification must be documented including a bladder map. Patients must have undergone a re-resection (second TURB in accordance with the EAU Guidelines) (i) if the initial TURB was incomplete (ii) if there was no muscle in the specimen after the initial TURB (except in TaG1/LG tumours) (iii) in all T1 and all G3/HG tumours TURB of T1 sites must include muscle. Re-resection must be negative in patients diagnosed with T1 and/or G3/HG and/or multiple tumours in the initial TURB. No UC in the upper tract, kidney and ureters. This should be confirmed by CT-IVU or IVU performed at time of initial diagnosis in selected cases as recommended in latest EAU guidelines published prior to screening. No UC in the urethra, excluded by visual inspection during cystoscopy and, in addition, in patients with (i) tumour of trigone (ii) tumour of bladder neck (iii) abnormal prostatic urethra UC must be excluded by biopsy of the prostatic urethra in all male patients or, in female patients, from the portion of the urethra adjacent to the bladder neck, before study recruitment. All patients must have urine cytology dated within the screening period prior to randomisation. Age ≥ 18 yrs Normal kidneys and ureters. Pre-treatment haematology and biochemistry values within acceptable limits: (i) haemoglobin ≥ 10 g/dl (g/100 ml) (ii) platelets ≥ 150 x 109/L (103/mm3) (iii) WBC ≥ 3.0 x 109/L (103/mm3) (iv) ANC ≥ 1.5 x 109/L (103/mm3, absolute neutrophil count) (v) Serum creatinine, SGOT, SGPT, Alkaline phosphatase: < 1.5 x UNL (upper normal limit) Negative pregnancy test for women of child-bearing potential A life expectancy at least of the duration of the trial. Unfit or unwilling to have a full or partial cystectomy. Signed informed consent. Exclusion Criteria: UC involving the prostatic urethra Non-UC tumour of the urinary tract Upper tract and intramural tumours (e.g. in Ostium). History of stage > T1 UC. CIS (suspected or present). Known or suspected reduced bladder capacity. Patients will have a US estimation of maximum bladder capacity or void spontaneously the maximum they can retain in their bladder, and this will be used to determine urine volume. A minimum volume of 250 ml is required. Bleeding disorder Macrohaematuria of ≥ 250 RBC's/uL or equivalent (e.g. > "+++" erythrocytes in a dipstick analysis). Pregnant or lactating women. Women of childbearing potential unwilling or unable to use adequate contraception if sexually active. More than a maintenance dose of oral corticosteroids (maintenance dose defined as the same dose regimen over the past 6 months for a condition requiring continual corticosteroid treatment) or patients with an immuno-compromised state for any reason. More than low-dose Methotrexate (>17.5 mg once a week). Other malignancy within the past five years, except: non-melanomatous skin cancer cured by excision, adequately treated carcinoma in situ of the cervix or ductal CIS (DCIS)/lobular CIS (LCIS) of the breast or stable prostate cancer (under active surveillance or hormone control) with a life expectancy of more than 5 years. Any known allergy or adverse event that would prevent them from receiving a treatment that they may be randomised to within the trial. Known untreated strictural disease or bladder neck contracture or any other condition that may prevent catheterisation with 21F catheter. Patients may undergo dilation or urethral incision before entering the study. Bladder diverticula with cumulative diameter > 1cm UTI at any time within 6 months preceding randomisation. Significant urinary incontinence (spontaneous, requiring use of pads) History of pelvic irradiation Patients with implanted electronic devices (such as cardiac pacemakers) unless they receive permission from their treating physician (e.g., cardiologist) and are monitored by a treating physician during the treatment session. Participation in another study which includes treatment that is liable to have an effect on this study.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Igal Ruvinsky, PhD
    Organizational Affiliation
    Medical Enterprises Europe B.V.
    Official's Role
    Study Director
    First Name & Middle Initial & Last Name & Degree
    Gerson Luedecke, Dr. med.
    Organizational Affiliation
    Universitätsklinikum Gießen und Marburg
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Links:
    URL
    http://www.synergo-medical.com/#!ongoing-clinical-trials-en/cx81
    Description
    Medical Enterprises ongoing trials

    Learn more about this trial

    SHTC - EUROPE-1 Synergo Hyperthermia-Chemotherapy by European Urologists' Research Operation Preserving Evolution Study I

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