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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02254915
Recruitment Status : Withdrawn (Shortages of the active comparator drug (BCG) on the market worldwide and a growing uncertainty as to its future supply.)
First Posted : October 2, 2014
Last Update Posted : April 1, 2015
Information provided by (Responsible Party):
Medical Enterprises Europe B.V.

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.

Condition or disease Intervention/treatment Phase
Urinary Bladder Neoplasms Urologic Neoplasms Urogenital Neoplasms Neoplasms Neoplasms by Site Urinary Bladder Diseases Urologic Diseases Device: Synergo + MMC Drug: Bacillus Calmette-Guérin Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Estimated Primary Completion Date : January 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Fever

Arm Intervention/treatment
Experimental: Synergo + MMC
Synergo radiofrequency (RF)-Induced hyperthermia-chemotherapy (SHTC) with mitomycin C (RITE) intravesical therapy as first-line adjuvant treatment for intermediate and high-risk NMIBC,
Device: Synergo + MMC
Synergo radiofrequency (RF)-Induced hyperthermia-chemotherapy with mitomycin C (RITE). Intravesical instillation of MMC utilizing the Synergo system.
Other Names:
  • RITE
  • SHTC

Active Comparator: Bacillus Calmette-Guérin
Intravesical BCG therapy as first-line adjuvant treatment for intermediate and high-risk NMIBC,
Drug: Bacillus Calmette-Guérin
Intravesical instillation of BCG.
Other Name: BCG

Primary Outcome Measures :
  1. RFS time [ Time Frame: 2 years ]
    The recurrence-free survival time in patients with NMIBC following treatment with SHTC (investigational arm) compared to BCG (controlled arm).

Secondary Outcome Measures :
  1. Progression-free survival time [ Time Frame: 2 years ]
  2. Recurrence free survival time by risk group [ Time Frame: 2 years ]
  3. Organ preservation rate [ Time Frame: 2 years ]
  4. Overall survival time [ Time Frame: 2 years ]
  5. Disease-specific survival time [ Time Frame: 2 years ]
  6. Adverse events [ Time Frame: 2 years ]
    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.

  7. Treatment discontinuation [ Time Frame: 2 years ]
    Proportion of treatment discontinuation of SHTC compared to BCG

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02254915

Sponsors and Collaborators
Medical Enterprises Europe B.V.
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Study Director: Igal Ruvinsky, PhD Medical Enterprises Europe B.V.
Principal Investigator: Gerson Luedecke, Dr. med. Universitätsklinikum Gießen und Marburg
Additional Information:
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Responsible Party: Medical Enterprises Europe B.V. Identifier: NCT02254915    
Other Study ID Numbers: CLN-002-00
First Posted: October 2, 2014    Key Record Dates
Last Update Posted: April 1, 2015
Last Verified: March 2015
Keywords provided by Medical Enterprises Europe B.V.:
Non Muscle Invasive Bladder Cancer
Superficial Bladder Cancer
Urothelial Cell Cancer
Transitional Cell Cancer
Additional relevant MeSH terms:
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Urinary Bladder Neoplasms
Neoplasms by Site
Urogenital Neoplasms
Urologic Neoplasms
Urologic Diseases
Urinary Bladder Diseases
Body Temperature Changes
BCG Vaccine
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs