Intravesical Adjuvant Electromotive Mitomycin-C

NCT ID: NCT01920269

Last Updated: 2013-08-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 331 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1994-01-31
• Study Completion Date: 2013-06-30

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.

Conditions

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

Keywords

non-muscle invasive bladder cancer; intravesical chemotherapy; mitomycin; passive diffusion; electromotive drug administration

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Trans-urethral resection

Intervention Type: PROCEDURE

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.

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.

Group Type: ACTIVE_COMPARATOR

Trans-urethral resection

Intervention Type: PROCEDURE

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.

intravesical passive diffusion mitomycin

Intervention Type: DRUG

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.

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.

Group Type: ACTIVE_COMPARATOR

Trans-urethral resection

Intervention Type: PROCEDURE

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.

intravesical passive diffusion mitomycin

Intervention Type: DRUG

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.

intravesical electromotive mitomycin

Intervention Type: DEVICE

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.

Interventions

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.

Intervention Type: PROCEDURE

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.

Intervention Type: DRUG

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.

Intervention Type: DEVICE

Other Intervention Names

Mitomycin-C

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of L'Aquila

OTHER

Sponsor Role: collaborator

University Of Perugia

OTHER

Sponsor Role: collaborator

University of Rome Tor Vergata

OTHER

Sponsor Role: lead

Responsible Party

Savino M. Di Stasi

Associate Professor of Urology, MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Savino M Di Stasi, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Tor Vergata University, Rome, Italy

Locations

Tor Vergata University, Department of experimental Medicine and Surgery/Urology

Rome, RM, Italy

Countries

Italy

Other Identifiers

UTV-72-1993

Identifier Type: -

Identifier Source: org_study_id