Intravesical Adjuvant Electromotive Mitomycin-C

NCT01920269 | Completed Phase 2 DMC

• 1 other identifier: UTV-72-1993
• Study Type: interventional
• Target: 331
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Time to progression

  120 months

Other Outcomes (2)

• Overall survival

  120 months

• Disease-specific survival

  120 months

Study Arms (3)

Transurethral resection alone

ACTIVE COMPARATOR

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

Intravesical passive diffusion mitomycin

ACTIVE COMPARATOR

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; Drug: intravesical passive diffusion mitomycin

Intravesical electromotive mitomycin

ACTIVE COMPARATOR

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; Drug: intravesical passive diffusion mitomycin; Device: intravesical electromotive mitomycin

Interventions

Trans-urethral resection 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 electromotive mitomycin; Intravesical passive diffusion mitomycin; Transurethral resection alone

intravesical passive diffusion mitomycin 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.

Also known as: Mitomycin-C

Intravesical electromotive mitomycin; Intravesical passive diffusion mitomycin

intravesical electromotive mitomycin 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.

Intravesical electromotive mitomycin

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Rome Tor Vergata: lead
• University of L'Aquila: collaborator
• University Of Perugia: collaborator

Study Sites (1)

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

Rome, RM, 00133, Italy

Location

MeSH Terms

Conditions

Non-Muscle Invasive Bladder Neoplasms

Interventions

Mitomycin

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Mitomycins; Indolequinones; Quinones; Organic Chemicals; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Savino M Di Stasi, MD, PhD

  Tor Vergata University, Rome, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Urology, MD, PhD

Study Record Dates

• First Submitted: August 7, 2013
• First Posted: August 9, 2013
• Study Start: January 1, 1994
• Primary Completion: December 1, 2004
• Study Completion: June 1, 2013
• Last Updated: August 9, 2013

Record last verified: 2013-08

Locations

IT (1)