Electromotive Mitomycin-C (EMDA-MMC) in Preventing Recurrences in High-risk Non-muscle-invasive Bladder Cancer

Last updated: March 31, 2021
Sponsor: Turku University Hospital
Overall Status: Active - Recruiting

Phase

3

Condition

Bladder Cancer

Urothelial Cancer

Urothelial Carcinoma

Treatment

N/A

Clinical Study ID

NCT03664869
Finnbladder-10
  • Ages > 18
  • All Genders

Study Summary

Disease recurrence and progression is a major issue in high risk non-muscle-invasive bladder cancer (NMIBC).

The current study compares two adjuvant instillation therapies in the treatment of high risk NMIBC. After resection of the tumour(s), patients will receive either traditional regimen of Bacillus Calmette-Guérin (BCG) instillations or combination treatment consisting of sequential BCG-instillations and mitomycin C instillations administered with electromotive drug administration (EMDA) device.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Histologically proven non-muscle-invasive tumour types confined to the urinary bladder
  • Carcinoma in situ with or without a papillary tumour(s)
  • Ta tumour(s) of high-grade
  • Any T1 tumour(s)
  • Written informed consent is required from every eligible patient
  • Second resection performed in case of T1 tumour
  • Adequate physical and mental condition to participate in the study (as judged bytreating physician

Exclusion

Exclusion Criteria:

  • Ta low grade tumour(s)
  • Muscle invasive (pT≥2) tumors
  • Urothelial cancer involving the prostatic urethra or upper urinary tract
  • Non-urothelial bladder cancer.
  • Prior BCG failure (If the patient has previously been successfully treated with BCG,and duration from the last instillation is >12 months, participation may beconsidered, if bladder preserving is chosen)
  • Prior or concurrent immunotherapy
  • Any medication or condition considered as contraindication to BCG or MMC (as judged bythe treating physician)
  • Urethral stricture, stone disease, chronic urinary tract infection or any otherurological condition that may comprise study participation (as judged by the treatingphysician)
  • Known allergy to MMC or BCG
  • Age < 18 years
  • Pregnancy or lactating patient
  • Other untreated or unstable malignancy in risk of recurrence/progression (as judged bythe treating physician)
  • Cardiac pacemaker
  • Expected survival time less than one year
  • Expected poor compliance

Study Design

Total Participants: 300
Study Start date:
October 26, 2018
Estimated Completion Date:
November 01, 2025

Study Description

Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease. The patients with NMIBC may be categorized in three risk groups according to the risk of recurrence and progression characterized by the disease. The treatment of high risk NMIBC includes a transurethral resection of the tumour(s), which is followed by an adjuvant instillation therapy, aiming to reduce the risk of recurrence and progression. Intravesical bacillus Calmette-Guérin (BCG) treatment is been the most effective single agent against NMIBC, and it is referred to as the gold standard in the treatment of high risk disease.

BCG is a solution of live, attenuated mycobacterium bovis bacteria, which is administered intravesically in an outpatient clinic. BCG activates an immunological reaction in the bladder wall, which leads to antitumour effect by activation of macrophages, T-cells, and natural killer (NK) cells. BCG treatment comprises an induction period, which includes six weekly instillations. This is followed by maintenance period including monthly or repeated series of three weekly instillations up to 1-3 years.

Other instillation therapies include intravesically administered chemotherapy. Mitomycin C (MMC) is the most used chemotherapeutic agent. MMC provides a better tolerated side effect profile, but is less effective against high risk NMIBC than BCG, when MMC is used as a single agent. Combinations of BCG- and MMC treatment has also been described with various results. The rationale for combining BCG and MMC is to enhance the absorption of BCG as MMC might cause disruption of bladder mucosa, which makes the mucosa more permeable thus enhancing the absorption of BCG. However, it is also hypothesized, that BCG may also work synergistic in favor of MMC.

The absorption and effect of MMC may be enhanced with electromotive drug administration (EMDA) device. After instillation of MMC, an electric field is conducted in the bladder with EMDA device via catheter and electrodes, which are placed in the bladder and lower abdomen skin. Electric field creates movement of sodium ions and water into the bladder wall, which creates electro-osmotic drag of MMC molecules. In a laboratory setting, EMDA-MMC instillation results in 4-7 times greater concentration of MMC in the deeper layers of the bladder wall than passively administered MMC instillation. EMDA-MMC treatment may also be combined with BCG treatment administering BCG and EMDA-MMC instillations sequentially. Results from a prospective randomized trial suggested, that sequential EMDA-MMC and BCG treatment might be even more effective against NMIBC than BCG therapy alone in terms of recurrence, progression and overall survival.

The current study is a prospective, open label, phase III randomized study allocating patients with high risk NMIBC to receive adjuvant instillation therapy either as traditional BCG treatment, or sequential BCG- and EMDA-MMC treatment. The aim of the study is to compare effectiveness and tolerability of the two treatment regimens in preventing recurrence and progression of high risk NMIBC.

Connect with a study center

  • HYKS Peijas Hospital

    Helsinki, 00029
    Finland

    Active - Recruiting

  • Jyväskylä Central Hospital

    Jyväskylä, 40620
    Finland

    Active - Recruiting

  • Päijät-Häme Central hospital

    Lahti, 15850
    Finland

    Active - Recruiting

  • Mikkeli Central Hospital

    Mikkeli, 50100
    Finland

    Active - Recruiting

  • Seinäjoki Central Hospital

    Seinäjoki, 60220
    Finland

    Active - Recruiting

  • Tampere University Hospital

    Tampere, 33521
    Finland

    Active - Recruiting

  • Turku University Hospital

    Turku, 20521
    Finland

    Active - Recruiting

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