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

Bladder Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00024349
• Other study ID #: CDR0000068921
• Secondary ID: CRC-BC2001EU-200
• Status: Completed
• Phase: Phase 3
• First received: September 13, 2001
• Last updated: December 17, 2013
• Start date: June 2001
• Est. completion date: April 2012

Study information

• Verified date: May 2007
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 350
• Est. completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Drug:
• fluorouracil

• mitomycin C

Radiation:
• radiation therapy

Locations

Country	Name	City	State
United Kingdom	Royal United Hospital	Bath	England
United Kingdom	Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust	Birmingham	England
United Kingdom	Royal Bournemouth Hospital NHS Trust	Bournemouth	England
United Kingdom	Sussex Cancer Centre at Royal Sussex County Hospital	Brighton	England
United Kingdom	Bristol Haematology and Oncology Centre	Bristol	England
United Kingdom	Addenbrooke's Hospital	Cambridge	England
United Kingdom	Cheltenham General Hospital	Cheltenham	England
United Kingdom	Essex County Hospital	Colchester	England
United Kingdom	Walsgrave Hospital	Coventry	England
United Kingdom	Derbyshire Royal Infirmary	Derby	England
United Kingdom	Royal Devon and Exeter Hospital	Exeter	England
United Kingdom	St. Luke's Cancer Centre at Royal Surrey County Hospital	Guildford	England
United Kingdom	Princess Royal Hospital at Hull and East Yorkshire NHS Trust	Hull	England
United Kingdom	St. Thomas' Hospital	London	England
United Kingdom	Maidstone Hospital	Maidstone	England
United Kingdom	Clatterbridge Centre for Oncology	Merseyside	England
United Kingdom	James Cook University Hospital	Middlesbrough	England
United Kingdom	Northern Centre for Cancer Treatment at Newcastle General Hospital	Newcastle-Upon-Tyne	England
United Kingdom	Northampton General Hospital NHS Trust	Northampton	England
United Kingdom	Glan Clwyd Hospital	Rhyl	Wales
United Kingdom	Royal Shrewsbury Hospital	Shrewsbury	England
United Kingdom	Royal Marsden NHS Foundation Trust - Surrey	Sutton	England
United Kingdom	Torbay Hospital	Torquay	England
United Kingdom	Good Hope Hospital Trust	West Midlands	England
United Kingdom	Southend University Hospital NHS Foundation Trust	Westcliff-On-Sea	England
United Kingdom	Worthing Hospital	Worthing	England
United Kingdom	Yeovil District Hospital	Yeovil	England

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Birmingham

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

James ND, Hussain SA, Hall E, Jenkins P, Tremlett J, Rawlings C, Crundwell M, Sizer B, Sreenivasan T, Hendron C, Lewis R, Waters R, Huddart RA; BC2001 Investigators. Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Loco-regional disease free survival at 2 years			No
Secondary	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			Yes
Secondary	Acute toxicity and cystoscopic local control at 3 months, 1 year, and 2 years			Yes
Secondary	Rate of salvage cystectomy			No
Secondary	Overall survival			No