2X2 Factorial Randomized Phase III Study Comparing Standard Versus Reduced Volume Radiotherapy With and Without Synchronous Chemotherapy in Muscle Invasive Bladder Cancer
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Enrollment
- 350
- Locations
- 54
- Primary Endpoint
- Loco-regional disease free survival at 2 years
Study Overview
Brief Summary
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
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).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Primary Purpose
- Treatment
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion 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
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Performance status:
- •Life expectancy:
- •Not specified
- •Hematopoietic:
- •WBC greater than 4,000/mm^3
- •Platelet count greater than 100,000/mm^3
- •Bilirubin less than 1.5 times upper limit of normal (ULN)
- •ALT or AST less than 1.5 times ULN
- •Glomerular filtration rate greater than 25 mL/min
- •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
- •See Disease Characteristics
- •No bilateral hip replacements
- •No concurrent metronidazole during fluorouracil administration
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Loco-regional disease free survival at 2 years
Secondary Outcomes
- 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
- Rate of salvage cystectomy
- Acute toxicity and cystoscopic local control at 3 months, 1 year, and 2 years
- Overall survival