Intravesical Adjuvant Electromotive Mitomycin-C

Bladder Cancer TNM Staging Primary Tumor (T) T1 Clinical Trial

— EMDA/MMC  

Official title:

Intravesical Adjuvant Electromotive Mitomycin-C in Patients With pTa-pT1 and G1-G2 Non-muscle Invasive Bladder Cancer: a Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01920269
• Other study ID #: UTV-72-1993
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: August 7, 2013
• Last updated: August 8, 2013
• Start date: January 1994
• Est. completion date: June 2013

Study information

• Verified date: August 2013
• Source: University of Rome Tor Vergata
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 331
• Est. completion date: June 2013
• Est. primary completion date: December 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 90 Years

Eligibility

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 × 10?/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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bladder Cancer TNM Staging Primary Tumor (T) T1
• Bladder Cancer TNM Staging Primary Tumor (T) Ta
• Bladder Cancer Transitional Cell Grade
• Urinary Bladder Neoplasms

Intervention

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.

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.

Locations

Country	Name	City	State
Italy	Tor Vergata University, Department of experimental Medicine and Surgery/Urology	Rome	RM

Sponsors (3)

Lead Sponsor	Collaborator
University of Rome Tor Vergata	University of L'Aquila, University Of Perugia

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overall survival	Time from randomisation until death from any cause	120 months	Yes
Other	Disease-specific survival	Time from randomisation until death from bladder cancer.	120 months	Yes
Primary	Disease-free interval	Time from randomisation to first cystoscopy noting recurrence as recorded by pathological assessment of transurethral-resection samples or biopsy samples	120 months	Yes
Secondary	Time to progression	time from randomisation until the onset of muscle invasive disease as recorded by pathological assessment of transurethral-resection samples or biopsy samples	120 months	Yes