RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy such as fluorouracil and mitomycin use different ways to stop tumor cells from dividing so they stop growing or die. Fluorouracil and mitomycin may make the tumor cells more sensitive to radiation therapy. It is not yet known if radiation therapy is more effective with or without chemotherapy in treating bladder cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy to all or part of the bladder with or without chemotherapy in treating patients who have stage II or stage III bladder cancer.

Condition	Treatment or Intervention	Phase
stage II bladder cancer stage III bladder cancer transitional cell carcinoma of the bladder squamous cell carcinoma of the bladder adenocarcinoma of the bladder	Drug: fluorouracil  Drug: mitomycin  Procedure: chemotherapy  Procedure: radiation therapy  Procedure: radiosensitization	Phase III

Further Study Details: 

OBJECTIVES:

• Compare the efficacy of standard volume radiotherapy vs reduced volume radiotherapy with or without synchronous fluorouracil and mitomycin in patients with stage II or III (muscle invasive) bladder cancer.
• Compare the toxicity of these regimens in these patients.
• Determine whether reducing the amount of bladder treated with the maximum dose of radiotherapy reduces the toxicity of radiotherapy without impacting local control in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, prior neoadjuvant chemotherapy (yes vs no), and intent to enter only 1 of the possible 2 randomizations on study (yes vs no). Patients are randomized to one of four treatment arms.

• Arm I: Patients undergo standard radiotherapy once daily 5 days a week for 4 or 6.5 weeks. Patients also receive synchronous chemotherapy comprising mitomycin IV on day 1 and fluorouracil IV continuously over days 1-5 and 16-20 during radiotherapy.
• Arm II: Patients undergo reduced volume radiotherapy once daily 5 days a week for 4 or 6.5 weeks. Patients also receive chemotherapy as in arm I.
• Arm III: Patients undergo standard radiotherapy as in arm I (without chemotherapy).
• Arm IV: Patients undergo reduced volume radiotherapy as in arm II (without chemotherapy). If standard radiotherapy is clearly indicated (e.g., patients with multiple tumors) patients may be randomized to standard radiotherapy with or without chemotherapy (arms I or III above). If chemotherapy is clearly contraindicated, patients are randomized to standard or reduced volume radiotherapy without chemotherapy (arms III or IV above).

Quality of life is assessed at baseline, at the end of therapy, at 6 and 12 months post-randomization, and then annually for at least 5 years.

Patients are followed at 6, 9, and 12 months post-randomization and then at least annually thereafter.

PROJECTED ACCRUAL: A total of 480 patients (120 per treatment arm) will be accrued for this study within 3 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed invasive bladder cancer (T2-4a, N0, M0)
• Adenocarcinoma
• Transitional cell carcinoma
• Squamous cell carcinoma
• Localized muscle invasion by surgery or imaging
• Patients with multiple tumors at time of study are ineligible for reduced volume radiotherapy but may be treated with standard volume radiotherapy on study

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• WHO 0-2

Life expectancy:

• Not specified

Hematopoietic:

• WBC greater than 4,000/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic:

• Bilirubin less than 1.5 times upper limit of normal (ULN)
• ALT or AST less than 1.5 times ULN

Renal:

• Glomerular filtration rate greater than 25 mL/min

Other:

• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception
• No inflammatory bowel disease
• No other prior malignancy within the past 2 years except adequately treated basal cell skin cancer or carcinoma in situ of the cervix
• No other prior malignancy or uncontrolled systemic disease that would preclude study participation

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy to the pelvis

Surgery:

• See Disease Characteristics
• No bilateral hip replacements

Other:

• No concurrent metronidazole during fluorouracil administration

United Kingdom, England
      Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust, Cambridge,  England,  CB2 2QQ,  United Kingdom; Recruiting
      Bristol Haematology and Oncology Centre, Bristol,  England,  BS2 8ED,  United Kingdom; Recruiting
      Cheltenham General Hospital, Cheltenham,  England,  GL53 7AN,  United Kingdom; Recruiting
      Clatterbridge Centre for Oncology NHS Trust, MERSEYSIDE,  England,  CH63 4JY,  United Kingdom; Recruiting
      Derbyshire Royal Infirmary, Derby,  England,  DE1 2QY,  United Kingdom; Recruiting
      Essex County Hospital, Colchester,  England,  C03 3NB,  United Kingdom; Recruiting
      Good Hope Hospital Trust, West Midlands,  England,  B75 7RR,  United Kingdom; Recruiting
      Guy's and St. Thomas' Hospitals NHS Foundation Trust, London,  England,  SE1 9RT,  United Kingdom; Recruiting
      Maidstone Hospital, Maidstone,  England,  ME16 9QQ,  United Kingdom; Recruiting
      Northampton General Hospital NHS Trust, Northampton,  England,  NN1 5BD,  United Kingdom; Recruiting
      Northern Centre for Cancer Treatment at Newcastle General Hospital, Newcastle upon Tyne,  England,  NE4 6BE,  United Kingdom; Recruiting
      Princess Royal Hospital, Hull,  England,  HU8 9HE,  United Kingdom; Recruiting
      Queen Elizabeth Hospital at University of Birmingham, Birmingham,  England,  B15 2TT,  United Kingdom; Recruiting
      Royal Bournemouth Hospital, Bournemouth,  England,  BH7 7DW,  United Kingdom; Recruiting
      Royal Devon and Exeter Hospital, Exeter,  England,  EX2 5DW,  United Kingdom; Recruiting
      Royal Marsden NHS Foundation Trust - Surrey, Sutton,  England,  SM2 5PT,  United Kingdom; Recruiting
      Royal Shrewsbury Hospital, Shrewsbury,  England,  SY3 8XQ,  United Kingdom; Recruiting
      Royal Sussex County Hospital, Brighton,  England,  BN2 5BF,  United Kingdom; Recruiting
      Royal United Hospital, Bath,  England,  BA1 3NG,  United Kingdom; Recruiting
      South Tees Hospitals NHS Trust, Middlesbrough, Cleveland,  England,  TS4 3BW,  United Kingdom; Recruiting
      Southend NHS Trust Hospital, Westcliff-On-Sea,  England,  SS0 0RY,  United Kingdom; Recruiting
      St. Luke's Cancer Centre at Royal Surrey County Hospital, Guildford,  England,  GU2 5XX,  United Kingdom; Recruiting
      Torbay Hospital, Torquay Devon,  England,  TQ2 7AA,  United Kingdom; Recruiting
      Walsgrave Hospital, Coventry,  England,  CV2 2DX,  United Kingdom; Recruiting
      Worthing Hospital, Worthing,  England,  BN11 2DH,  United Kingdom; Recruiting
      Yeovil District Hospital, Yeovil - Somerset,  England,  BA21 4AT,  United Kingdom; Recruiting
United Kingdom, Wales
      Glan Clywd District General Hospital, Rhyl,  Wales,  LL18 5UG,  United Kingdom; Recruiting

Study chairs or principal investigators

Nicholas James, MD,  Study Chair,  Queen Elizabeth Hospital at University of Birmingham   

Study ID Numbers:  CDR0000068921; CRC-BC2001; EU-20052; NCT00024349
Record last reviewed:  May 2003
Last Updated:  March 3, 2005
Record first received:  September 13, 2001
ClinicalTrials.gov Identifier:  NCT00024349
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08