RATIONALE: Biological therapies such as BCG use different ways to stimulate the immune system and stop tumor cells from growing. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with biological therapy may kill more tumor cells. It is not yet known if BCG is more effective with or without mitomycin.

PURPOSE: Randomized phase II trial to compare the effectiveness of BCG plus mitomycin with that of BCG alone in treating patients who have bladder cancer.

Condition	Treatment or Intervention	Phase
stage 0 bladder cancer recurrent bladder cancer transitional cell carcinoma of the bladder	Drug: BCG  Drug: mitomycin  Procedure: adjuvant therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: conventional surgery  Procedure: non-specific immune-modulator therapy  Procedure: surgery	Phase II

Further Study Details: 

OBJECTIVES:

• Compare the complete response rate of patients with carcinoma in situ of the bladder treated with adjuvant intravesical BCG with or without intravesical mitomycin following transurethral resection.
• Compare the disease-free interval and type of recurrence after complete response in patients treated with these regimens.
• Compare the side effects of these regimens in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are randomized to one of two treatment arms.

Arm I:

• Induction therapy: Patients receive intravesical mitomycin over 1 hour once weekly on weeks 1-6 and intravesical BCG once weekly on weeks 7-12. Patients with visible lesions or disease recurrence or progression undergo transurethral resection (TUR) during weeks 16-18 and receive one additional course of intravesical therapy.
• Maintenance therapy:Patients with a complete response after either course of induction therapy proceed to maintenance therapy comprising intravesical mitomycin once on week 1 and intravesical BCG once weekly on weeks 2 and 3. Maintenance therapy repeats every 6 months through year 3.

Arm II:

• Induction therapy:Patients receive intravesical BCG once weekly on weeks 1-6 and 10-12. Patients with visible lesions or disease recurrence or progression undergo transurethral resection (TUR) during weeks 16-18 and receive one additional course of intravesical therapy.
• Maintenance therapy: Patients with a complete response after either course of induction therapy receive maintenance therapy comprising intravesical BCG once weekly on weeks 1-3. Maintenance therapy repeats every 6 months through year 3. Patients are followed every 6 months for 5 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 84-126 patients (42-63 per treatment arm) will be accrued for this study within 3.5 years.

Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed carcinoma in situ (CIS) of the bladder with urinary cytology
• Primary CIS (no prior history of CIS, papillary, or solid transitional cell carcinoma [TCC] of the bladder and no concurrent papillary or solid TCC) OR
• Secondary CIS (detected after complete resection of superficial Ta/T1 TCC of the bladder) OR
• Concurrent CIS (in the presence of superficial primary or recurrent Ta/T1 TCC of the bladder)
• No more than 28 days since prior transurethral resection (TUR) of all visible lesions
• No muscle involvement
• No prior or concurrent upper urinary tract tumors
• No urethral strictures that would prevent endoscopic procedures and repeated catheterization
• No upper urinary tract disease (e.g., vesico-ureteral reflux or massive stones) that would make multiple transurethral procedures risky

PATIENT CHARACTERISTICS: Age:

• Not specified

Performance status:

• WHO 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Other:

• Not pregnant or nursing
• No active tuberculosis (highly positive skin tests allowed if no active disease)
• No disease that would preclude general anesthesia
• No active intractable or uncontrollable infection
• No other prior or concurrent malignancy except cured basal cell skin cancer
• No psychological, familial, sociological, or geographical condition that would preclude study participation

PRIOR CONCURRENT THERAPY: Biologic therapy:

• No prior BCG

Chemotherapy:

• More than 3 months since prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy to the pelvis

Surgery:

• See Disease Characteristics

Other:

• More than 3 months since prior intravesical cytostatic agents

Belgium
      Academisch Ziekenhuis der Vrije Universiteit Brussel, Brussels,  1090,  Belgium
      Cazk Groeninghe - Campus Maria's Voorzienigheid, Kortrijk,  B-8500,  Belgium
      Onze Lieve Vrouw Ziekenhuis Aalst, Aalst,  B-9300,  Belgium
      Universitair Ziekenhuis Gent, Ghent,  B-9000,  Belgium
      Virga Jesse Hospital, Hasselt,  3500,  Belgium
Italy
      Azienda Ospedaliera Maggiore Della Carita, Novara,  28100,  Italy
      Ospedale di Circolo e Fondazione Macchi, Varese,  21100,  Italy
      Universita Degli Studi Di Pisa, Pisa,  56126,  Italy
Netherlands
      Academisch Medisch Centrum, Amsterdam,  1105 AZ,  Netherlands
      Academisch Ziekenhuis Maastricht, Maastricht,  6202 AZ,  Netherlands
      Daniel Den Hoed Cancer Center at Erasmus Medical Center, Rotterdam,  3008 AE,  Netherlands
      University Medical Center Nijmegen, Nijmegen,  NL-6500 HB,  Netherlands
Portugal
      Hospital Desterro, Amadora,  P-2700,  Portugal
Turkey
      Dokuz Eylul University School of Medicine, Izmir,  35340,  Turkey
United Kingdom, England
      Bristol Royal Infirmary, Bristol,  England,  BS2 8HW,  United Kingdom
United Kingdom, Wales
      University of Wales College of Medicine, Cardiff,  Wales,  CF14 4XN,  United Kingdom

Study chairs or principal investigators

Aldo V. Bono, MD,  Ospedale di Circolo e Fondazione Macchi   

Study ID Numbers:  CDR0000068869; EORTC-30993; AURO-EORTC-30993; FINNBLADDER-EORTC-30993; GAUO-EORTC-30993; SEUG-EORTC-30993; UKCCCR-EORTC-30993; NCRI-EORTC-30993; NCT00023842
Record last reviewed:  March 2005
Last Updated:  March 10, 2005
Record first received:  September 13, 2001
ClinicalTrials.gov Identifier:  NCT00023842
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08