Intravesical Adjuvant Electromotive Mitomycin-C (EMDA/MMC)

University of Rome Tor Vergata

Status and phase: Completed; Phase 3; Phase 2

Conditions: Bladder Cancer Transitional Cell Grade; Bladder Cancer TNM Staging Primary Tumor (T) T1; Bladder Cancer TNM Staging Primary Tumor (T) Ta

Treatments: Procedure: Trans-urethral resection; Device: intravesical electromotive mitomycin; Drug: intravesical passive diffusion mitomycin

Study type: Interventional

Funder types: Other

Identifiers

NCT01920269

UTV-72-1993

Details and patient eligibility

About

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.

Enrollment: 331 patients

Sex: All

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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331 participants in 3 patient groups

Transurethral resection alone

Active Comparator group

Description:

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.

Treatment:

Procedure: Trans-urethral resection

Intravesical passive diffusion mitomycin

Active Comparator group

Description:

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.

Treatment:

Drug: intravesical passive diffusion mitomycin

Procedure: Trans-urethral resection

Intravesical electromotive mitomycin

Active Comparator group

Description:

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.

Treatment:

Device: intravesical electromotive mitomycin

Drug: intravesical passive diffusion mitomycin

Procedure: Trans-urethral resection