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Intravesical Adjuvant Electromotive Mitomycin-C (EMDA/MMC)

Primary Purpose

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

Status

Completed

Phase

Phase 2

Locations

Italy

Study Type

Interventional

Intervention

Trans-urethral resection

intravesical passive diffusion mitomycin

intravesical electromotive mitomycin

About this trial

This is an interventional treatment trial for Bladder Cancer TNM Staging Primary Tumor (T) Ta focused on measuring non-muscle invasive bladder cancer, intravesical chemotherapy, mitomycin, passive diffusion, electromotive drug administration

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Arm Label

Transurethral resection alone

Intravesical passive diffusion mitomycin

Intravesical electromotive mitomycin

Arm 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.

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.

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.

Outcomes

Primary Outcome Measures

Disease-free interval

Time from randomisation to first cystoscopy noting recurrence as recorded by pathological assessment of transurethral-resection samples or biopsy samples

Secondary Outcome Measures

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

Full Information

NCT ID

NCT01920269

First Posted

August 7, 2013

Last Updated

August 8, 2013

Sponsor

University of Rome Tor Vergata

Collaborators

University of L'Aquila, University Of Perugia

1. Study Identification

Unique Protocol Identification Number

NCT01920269

Brief Title

Intravesical Adjuvant Electromotive Mitomycin-C

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2013

Overall Recruitment Status

Completed

Study Start Date

January 1994 (undefined)

Primary Completion Date

December 2004 (Actual)

Study Completion Date

June 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Rome Tor Vergata

Collaborators

University of L'Aquila, University Of Perugia

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

331 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Transurethral resection alone

Arm Type

Active Comparator

Arm Description

Arm Title

Intravesical passive diffusion mitomycin

Arm Type

Active Comparator

Arm Description

Arm Title

Intravesical electromotive mitomycin

Arm Type

Active Comparator

Arm 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.

Intervention Type

Procedure

Intervention Name(s)

Trans-urethral resection

Intervention Description

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

Drug

Intervention Name(s)

intravesical passive diffusion mitomycin

Other Intervention Name(s)

Mitomycin-C

Intervention Description

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

Device

Intervention Name(s)

intravesical electromotive mitomycin

Intervention Description

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 Measure Information:

Title

Disease-free interval

Description

Time from randomisation to first cystoscopy noting recurrence as recorded by pathological assessment of transurethral-resection samples or biopsy samples

Time Frame

120 months

Secondary Outcome Measure Information:

Title

Time to progression

Description

time from randomisation until the onset of muscle invasive disease as recorded by pathological assessment of transurethral-resection samples or biopsy samples

Time Frame

120 months

Other Pre-specified Outcome Measures:

Title

Overall survival

Description

Time from randomisation until death from any cause

Time Frame

120 months

Title

Disease-specific survival

Description

Time from randomisation until death from bladder cancer.

Time Frame

120 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Savino M Di Stasi, MD, PhD

Organizational Affiliation

Tor Vergata University, Rome, Italy

Official's Role

Principal Investigator

Facility Information:

Facility Name

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

City

Rome

State/Province

ZIP/Postal Code

00133

Country

Italy

12. IPD Sharing Statement

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Intravesical Adjuvant Electromotive Mitomycin-C

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