Radiation Therapy With or Without Chemotherapy in Treating Patients With Stage II or Stage III Bladder Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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. 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 two 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 standard radiotherapy as in arm I (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. Peer Reviewed and Funded or Endorsed by Cancer Research UK PROJECTED ACCRUAL: A total of 350 patients will be accrued for this study.

Official Title
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2X2 Factorial Randomized Phase III Study Comparing Standard Versus Reduced Volume Radiotherapy With and Without Synchronous Chemotherapy in Muscle Invasive Bladder Cancer

Conditions
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Bladder Cancer

Intervention / Treatment
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* Drug: fluorouracil
* Drug: mitomycin C
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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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 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: fluorouracil|nan|
|Drug: mitomycin C|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Loco-regional disease free survival at 2 years |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival, metastases-free survival, and late toxicity by RTOG and Lent Som toxicity scores, Bladder capacity, and patient assessed Fact-BL quality of life scores at 1 and 2 years |  |  | 
| Acute toxicity and cystoscopic local control at 3 months, 1 year, and 2 years |  |  | 
| Rate of salvage cystectomy |  |  | 
| Overall survival |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage II bladder cancer, stage III bladder cancer, transitional cell carcinoma of the bladder, squamous cell carcinoma of the bladder, adenocarcinoma of the bladder