RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs such as carbogen and niacinamide may make tumor cells more sensitive to radiation therapy. It is not yet known whether radiation therapy is more effective with or without carbogen and niacinamide in treating patients who have bladder cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy with or without carbogen and niacinamide in treating patients who have locally advanced bladder cancer.

Condition	Treatment or Intervention	Phase
stage I bladder cancer stage II bladder cancer stage III bladder cancer transitional cell carcinoma of the bladder	Drug: carbogen  Drug: niacinamide  Procedure: radiation therapy  Procedure: radiosensitization	Phase III

Further Study Details: 

OBJECTIVES:

• Compare the 6-month cystoscopic response in patients with locally advanced transitional cell carcinoma of the bladder treated with radical radiotherapy with or without radiosensitization with carbogen and niacinamide.
• Compare the local failure-free and overall disease-specific survival of patients treated with these regimens.
• Compare the treatment-related morbidity, in particular acute and chronic bowel and bladder symptoms, in patients treated with these regimens.
• Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive radical radiotherapy once daily, 5 days a week, for 4-6.4 weeks. Patients also receive oral niacinamide once daily 1.5-2 hours before initiation of each radiotherapy dose and carbogen through a closed breathing system (face mask with a tight air seal or a mouthpiece with nasal clip) once daily beginning 5 minutes before initiation and continuing until completion of each radiotherapy dose.
• Arm II: Patients receive radiotherapy as in arm I. Quality of life is assessed at baseline; at 4 weeks; at 3, 6, and 12 months; and then annually for 4 years.

Patients are followed at 8 and 12 weeks; at 6, 9, and 12 months; and then every 6 months for 4 years.

PROJECTED ACCRUAL: A total of 330 patients (165 per treatment arm) will be accrued for this study.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed transitional cell carcinoma of the bladder
• Muscle invasive carcinoma (stage T2 or T3) of any grade OR
• High-grade (G3) superficial bladder carcinoma (T1) OR
• Prostatic invasion (T4a)
• No squamous cell carcinoma or adenocarcinoma of the bladder
• No locally advanced T4b carcinoma
• No distant metastasis or enlarged pelvic lymph nodes on CT staging scan of the pelvis

PATIENT CHARACTERISTICS: Age:

• Over 18

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin no greater than 2 times normal

Renal:

• Creatinine no greater than 2 times normal

Cardiovascular:

• No ischemic heart disease or peripheral vascular disease requiring diuretics or angiotensin-converting enzyme inhibitors

Pulmonary:

• No concurrent respiratory disease with reduced respiratory drive that would preclude the delivery of 95% oxygen

Other:

• Capable of complying with a closed breathing system delivering carbogen through either a mask or a mouthpiece with nasal clip

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

United Kingdom, England
      Bristol Haematology and Oncology Centre, Bristol,  England,  BS2 8ED,  United Kingdom; Recruiting
      Cancer Research Centre at Weston Park Hospital, Sheffield,  England,  S1O 2SJ,  United Kingdom; Recruiting
      Christie Hospital N.H.S. Trust, Manchester,  England,  M20 4BX,  United Kingdom; Recruiting
      Clatterbridge Centre for Oncology NHS Trust, MERSEYSIDE,  England,  CH63 4JY,  United Kingdom; Recruiting
      Cookridge Hospital at Leeds Teaching Hospital NHS Trust, Leeds,  England,  LS16 6QB,  United Kingdom; Recruiting
      Derbyshire Royal Infirmary, Derby,  England,  DE1 2QY,  United Kingdom; Recruiting
      Ipswich Hospital NHS Trust, Ipswich,  England,  IP4 5PD,  United Kingdom; Recruiting
      Kent and Canterbury Hospital, Canterbury,  England,  CT2 3NG,  United Kingdom; Recruiting
      Mount Vernon Hospital, Northwood,  England,  HA6 2RN,  United Kingdom; Recruiting
      Northern Centre for Cancer Treatment at Newcastle General Hospital, Newcastle upon Tyne,  England,  NE4 6BE,  United Kingdom; Recruiting
      Nottingham City Hospital NHS Trust, Nottingham,  England,  NG5 1PB,  United Kingdom; Recruiting
      Oldchurch Hospital, Romford,  England,  RM7 OBE,  United Kingdom; Recruiting
      Royal Sussex County Hospital, Brighton,  England,  BN2 5BF,  United Kingdom; Recruiting
United Kingdom, Wales
      Velindre Cancer Center at Velinde Hospital, Cardiff,  Wales,  CF14 2TL,  United Kingdom; Recruiting

Study chairs or principal investigators

Peter John Hoskin, MD,  Study Chair,  Mount Vernon Hospital   

Study ID Numbers:  CDR0000069283; MTVERNHOSP-BCON; EU-20051; NCT00033436
Record last reviewed:  April 2002
Last Updated:  March 3, 2005
Record first received:  April 9, 2002
ClinicalTrials.gov Identifier:  NCT00033436
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08