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Intravesical Adjuvant Electromotive Mitomycin-C (EMDA/MMC)

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ClinicalTrials.gov Identifier: NCT01920269
Recruitment Status : Completed
First Posted : August 9, 2013
Last Update Posted : August 9, 2013
Sponsor:
Collaborators:
University of L'Aquila
University Of Perugia
Information provided by (Responsible Party):
Savino M. Di Stasi, University of Rome Tor Vergata

Brief Summary:
In laboratory and clinical studies, intravesical electromotive drug administration increased mitomycin bladder uptake, improving clinical efficacy in high-risk non-muscle invasive urothelial bladder cancer. The investigators' aim was to compare transurethral resection of bladder tumor and adjuvant intravesical electromotive mitomycin with transurethral resection and adjuvant intravesical passive diffusion mitomycin and transurethral resection alone in patients with primary stage pTa-pT1 and grade G1-G2 urothelial bladder cancer Patients will be randomly assigned to: transurethral resection alone, transurethral resection and adjuvant intravesical 40 mg passive diffusion mitomycin dissolved in 50 ml sterile water infused over 60 minutes once a week for 6 weeks, or transurethral resection and adjuvant intravesical 40 mg electromotive mitomycin dissolved in 100 ml sterile water with 23 mA pulsed electric current for 30 minutes once a week for 6 weeks. Patients in the intravesical adjuvant electromotive and passive diffusion mitomycin groups who are disease-free 3 months after induction treatment, will be scheduled to receive monthly intravesical instillation for 10 months, with the same dose and methods of infusion as initial assigned treatment. All patients will be assessed for safety. The investigators' primary endpoints are recurrence rate and disease-free interval. Analyses will be done by intention to treat.

Condition or disease Intervention/treatment Phase
Bladder Cancer TNM Staging Primary Tumor (T) Ta Bladder Cancer TNM Staging Primary Tumor (T) T1 Bladder Cancer Transitional Cell Grade Procedure: Trans-urethral resection Drug: intravesical passive diffusion mitomycin Device: intravesical electromotive mitomycin Phase 2 Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 331 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Intravesical Adjuvant Electromotive Mitomycin-C in Patients With pTa-pT1 and G1-G2 Non-muscle Invasive Bladder Cancer: a Randomized Controlled Trial
Study Start Date : January 1994
Actual Primary Completion Date : December 2004
Actual Study Completion Date : June 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bladder Cancer

Arm Intervention/treatment
Active Comparator: Transurethral resection alone
Patients underwent urinary cytology, random cold-cup biopsies of the bladder and prostatic urethra—ie, and complete transurethral resection of all bladder tumour visible on endoscopy, ensuring muscle is included in resected samples. Response to treatment will be assessed with cystoscopy, biopsy and urinary cytology at 3-month intervals for 2 years, 6-month intervals for 3 years and yearly thereafter.
Procedure: Trans-urethral resection
Patients underwent urinary cytology of the bladder and upper urinary tract; random cold-cup biopsies of the bladder and prostatic urethra, and complete transurethral resection of all bladder tumour visible on endoscopy, ensuring muscle is included in resected samples.

Active Comparator: Intravesical passive diffusion mitomycin
Patients underwent urinary cytology, random cold-cup biopsies of the bladder and prostatic urethra, and complete transurethral resection of all bladder tumour visible on endoscopy, ensuring muscle is included in resected samples. Patients are scheduled to receive an initial 6 intravesical mitomycin treatments at weekly intervals commencing 2 weeks after endoscopic procedures. Patients are placed on fluid restriction and oral sodium bicarbonate before intravesical mitomycin treatments. Patients who have a complete response to the initial 6 weekly treatments underwent a further 10 monthly instillations. Response to treatment will be assessed with cystoscopy, biopsy and urinary cytology at 3-month intervals for 2 years, 6-month intervals for 3 years and yearly thereafter.
Procedure: Trans-urethral resection
Patients underwent urinary cytology of the bladder and upper urinary tract; random cold-cup biopsies of the bladder and prostatic urethra, and complete transurethral resection of all bladder tumour visible on endoscopy, ensuring muscle is included in resected samples.

Drug: intravesical passive diffusion mitomycin
A dose of 40 mg mitomycin dissolved in 50 ml sterile water is infused intravesically through a Foley catheter, retained in the bladder for 60 min with catheter clamping, and then drained. Patients who have a complete response to the initial 6 weekly treatments underwent a further 10 monthly instillations, with the same dose and methods of infusion as initial assigned treatment.
Other Name: Mitomycin-C

Active Comparator: Intravesical electromotive mitomycin
Patients underwent urinary cytology, random cold-cup biopsies of the bladder and prostatic urethra, and complete transurethral resection of all bladder tumour visible on endoscopy, ensuring muscle is included in resected samples. Patients are scheduled to receive an initial 6 intravesical mitomycin treatments at weekly intervals commencing 2 weeks after endoscopic procedures. Patients are placed on fluid restriction and oral sodium bicarbonate before intravesical mitomycin. Patients who have a complete response to the initial 6 weekly treatments underwent a further 10 monthly instillations. Response to treatment will be assessed with cystoscopy and urinary cytology at 3-month intervals for 2 years, 6-month intervals for 3 years and yearly thereafter.
Procedure: Trans-urethral resection
Patients underwent urinary cytology of the bladder and upper urinary tract; random cold-cup biopsies of the bladder and prostatic urethra, and complete transurethral resection of all bladder tumour visible on endoscopy, ensuring muscle is included in resected samples.

Drug: intravesical passive diffusion mitomycin
A dose of 40 mg mitomycin dissolved in 50 ml sterile water is infused intravesically through a Foley catheter, retained in the bladder for 60 min with catheter clamping, and then drained. Patients who have a complete response to the initial 6 weekly treatments underwent a further 10 monthly instillations, with the same dose and methods of infusion as initial assigned treatment.
Other Name: Mitomycin-C

Device: intravesical electromotive mitomycin
A dose of 40 mg mitomycin dissolved in 100 ml water is instilled and retained in the bladder for 30 minutes with 20 mA pulsed electric current, and then drained. Patients who have a complete response to the initial 6 weekly treatments underwent a further 10 monthly instillations with the same dose and methods of infusion as initial assigned treatment. Intravesical electromotive drug administration is given by a battery-powered generator delivering a controlled electric current that passes between the active intravesical electrode (integrated into a specific transurethral catheter) and dispersive ground electrodes (on skin of the lower abdomen). Operators set active electrode polarity and current intensity on the generator.




Primary Outcome Measures :
  1. Disease-free interval [ Time Frame: 120 months ]
    Time from randomisation to first cystoscopy noting recurrence as recorded by pathological assessment of transurethral-resection samples or biopsy samples


Secondary Outcome Measures :
  1. Time to progression [ Time Frame: 120 months ]
    time from randomisation until the onset of muscle invasive disease as recorded by pathological assessment of transurethral-resection samples or biopsy samples


Other Outcome Measures:
  1. Overall survival [ Time Frame: 120 months ]
    Time from randomisation until death from any cause

  2. Disease-specific survival [ Time Frame: 120 months ]
    Time from randomisation until death from bladder cancer.



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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • histologically proven primary stage pTa-pT1 urothelial bladder cancer,
  • adequate bone-marrow reserve (ie, white-blood-cell count ≥4000 × 10⁶ cells per L; platelet count ≥120 × 10⁹/L),
  • normal renal function (ie, serum creatinine ≤123·76 μmol/L),
  • normal liver function (ie, serum glutamic-oxaloacetic aminotransferase ≤42 U/L, serum glutamic-pyruvic aminotransferase ≤48 U/L, and total bilirubin ≤22 μmol/L),
  • Eastern Cooperative Oncology Group performance status between 0 and 2.

Exclusion Criteria:

  • non-urothelial carcinomas of the bladder;
  • previous or concomitant grade G3 urothelial and/or carcinoma in situ of the bladder;
  • urothelial carcinoma of the upper urinary tract and urethra, or both;
  • previous intravesical treatment with chemotherapeutic and immunotherapeutic drugs;
  • known allergy to mitomycin;
  • bladder capacity less than 200 mL;
  • untreated urinary-tract
  • infection; severe systemic infection (ie, sepsis);
  • treatment with immunosuppressive drugs;
  • urethral strictures that would prevent endoscopic procedures and catheterisation;
  • previous radiotherapy to the pelvis;
  • other concurrent chemo therapy, radio therapy, and treatment with biological response modifiers;
  • other malignant diseases within 5 years of trial registration (except for adequately treated basal-cell or squamous-cell skin cancer, in situ cervical cancer);
  • pregnancy;
  • any factors that would preclude study participation.

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 ClinicalTrials.gov identifier (NCT number): NCT01920269


Locations
Italy
Tor Vergata University, Department of experimental Medicine and Surgery/Urology
Rome, RM, Italy, 00133
Sponsors and Collaborators
University of Rome Tor Vergata
University of L'Aquila
University Of Perugia
Investigators
Principal Investigator: Savino M Di Stasi, MD, PhD Tor Vergata University, Rome, Italy

Responsible Party: Savino M. Di Stasi, Associate Professor of Urology, MD, PhD, University of Rome Tor Vergata
ClinicalTrials.gov Identifier: NCT01920269     History of Changes
Other Study ID Numbers: UTV-72-1993
First Posted: August 9, 2013    Key Record Dates
Last Update Posted: August 9, 2013
Last Verified: August 2013

Keywords provided by Savino M. Di Stasi, University of Rome Tor Vergata:
non-muscle invasive bladder cancer
intravesical chemotherapy
mitomycin
passive diffusion
electromotive drug administration

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Mitomycins
Mitomycin
Antibiotics, Antineoplastic
Antineoplastic Agents
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors