Hyperthermia Treatment in Conjunction With Mitomycin C Versus Bacillus Calmette-Guérin Immunotherapy (BCG) for Superficial Bladder Cancer

Phase 3

Terminated

• Conditions: Urinary Bladder Diseases; Neoplasms by Site; Urinary Bladder Cancer; Urologic Neoplasms; Malignant Tumor of Urinary Bladder; Urologic Diseases; Urinary Bladder Neoplasms; Neoplasms
• Interventions: Drug: Bacillus Calmette-Guérin; Device: Synergo + MMC

• Registration Number: NCT00384891
• Lead Sponsor: Medical Enterprises Europe B.V.

Brief Summary

The study is designed to compare the efficacy and safety of 2 treatment types for the prevention of tumor recurrence of superficial bladder cancer:

1. A combination of bladder wall heating and local chemotherapy (Synergo)

2. Bacillus Calmette-Guérin (BCG)

Detailed Description

The study is a randomized controlled study, designed to test the efficacy and safety of a new treatment modality for the prevention of tumor recurrence in superficial bladder cancer.

Patients must have their tumors surgically resected prior to study enrollment, and undergo a series of tests to prove their bladder is now free of tumor. Eligible patients will be randomly assigned to one of 2 treatment arms:

1. A combination of bladder wall heating and local chemotherapy (Synergo)

2. Bacillus Calmette-Guérin (BCG)

Patients will be treated during the first year of the study, and will be followed up for a total of 2 years. The follow up will include a visual evaluation of the patient's bladder by cystoscopy, a cytological examination of the urine (to look for malignant cells) and other additional exams. The patients' general welfare will be monitored through out the study.

The aim of this study is to compare the efficacy and safety of the novel treatment (Synergo) to that of the well-known BCG

Study Timeline

• Study Start: 2002-02
• Study First Submitted: 2006-10-05
• Study First Submitted QC: 2006-10-05
• Study First Posted: 2006-10-06
• Primary Completion: 2013-12
• Study Completion: 2013-12
• Status Verified: 2014-10
• Last Update Submitted: 2014-10-05
• Last Update Posted: 2014-10-07

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 190

Inclusion Criteria

• Superficial TCC: Any G3 or any T1 and/or CIS
• Multifocal (>1) Ta lesions
• Multiple recurrences (>2) of Ta lesions in the last 24 months
• Complete tumor eradication must be confirmed
• WHO performance status 0-2 (Appendix V)
• Life expectancy of more than 24 months
• Patients willing to sign informed consent

Exclusion Criteria

• Bladder tumors other than TCC
• Coexistence of another primary malignant tumor other than BCC of the skin
• TCC of the bladder involving the urethra or upper urinary tract
• Previous history of TCC stage T2 or higher
• Clinical presence or previous history of regional spreading or distant metastases
• Intravesical MMC treatments during the last 12 months
• Previous intravesical BCG therapy (Any intravesical BCG therapy in the last 24 months, or More than 6 BCG intravesical instillations in the last 48 months.
• Previous pelvic radiotherapy or systemic chemotherapy
• Partial cystectomy
• Diverticle of bladder larger than 1cm in diameter
• Residual urine > 100cc measured by uroflowmetry
• Bladder volume < 150cc measured by ultrasound
• Urinary incontinence (more than one wet pad a day)
• Urethral stricture impeding 20F catheterization
• Urethral bleeding or persistent hematuria
• Active intractable or uncontrollable UTI
• Active tuberculosis or BCG infection
• Patients who experienced BCG life threatening sepsis
• Known allergy to MMC or BCG
• Known impaired immune response, positive HIV serology, patients receiving systemic steroids or immunosuppressive therapy
• Hematological disorders; leukocytes < 3500, platelets < 100,000
• Kidney or liver function disorders (more than 1.5 times upper normal limit)
• Pregnant or lactating women
• Patients who cannot be followed up properly or are unable to collaborate

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bacillus Calmette-Guérin	Bacillus Calmette-Guérin	Intravesical instillation with BCG (Bacillus Calmette-Guérin)
Synergo + MMC	Synergo + MMC	Combined bladder wall hyperthermia and intravesical instillation with cooled Mitomycin-C

Primary Outcome Measures

Name	Time	Method
Recurrence free survival	2 years	Recurrence free survival probability of STCCB in patients with pure (non-CIS) papillary tumor

Secondary Outcome Measures

Name	Time	Method
Proportion of complete response in CIS patients	3 months
Progression rate (to disease stage>T1) and/or metastatic disease	2 years
Local and systemic side effects, both subjective and objective	2 years

Trial Locations

Locations (8)

Department of Urology, Radboud University Hospital; 🇳🇱 Nijmegen, Netherlands

University Hospital - AKH Vienna; 🇦🇹 Vienna, Austria

Wolfson Hospital; 🇮🇱 Holon, Israel

Hadassah University Hospital; 🇮🇱 Jerusalem, Israel

Bnai Zion Medical Center; 🇮🇱 Haifa, Israel

Istituto Europeo del Oncologia; 🇮🇹 Milan, Italy

Galliera Hospital; 🇮🇹 Genova, Italy

San Raffaele Hospital (HSR); 🇮🇹 Milan, Italy