Clinical trial NCT00024349: Radiation Therapy With or Without Chemotherapy in Treating Patients With Stage II or Stage III Bladder Cancer
Official title: 2X2 Factorial Randomized Phase III Study Comparing Standard Versus Reduced Volume Radiotherapy With and Without Synchronous Chemotherapy in Muscle Invasive Bladder Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bladder Cancer
Keywords: stage II bladder cancer
stage III bladder cancer
transitional cell carcinoma of the bladder
squamous cell carcinoma of the bladder
adenocarcinoma of the bladder
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

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).

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.

Eligibility 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:

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

Primary outcomes:
measure: Loco-regional disease free survival at 2 years
Secondary outcomes:
measure: 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
measure: Acute toxicity and cystoscopic local control at 3 months, 1 year, and 2 years
measure: Rate of salvage cystectomy
measure: Overall survival
Other outcomes:
Locations:
city: Bath
country: United Kingdom
facility: Royal United Hospital
state: England
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
state: England
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital NHS Trust
state: England
city: Brighton
country: United Kingdom
facility: Sussex Cancer Centre at Royal Sussex County Hospital
state: England
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: England
city: Cheltenham
country: United Kingdom
facility: Cheltenham General Hospital
state: England
city: Colchester
country: United Kingdom
facility: Essex County Hospital
state: England
city: Coventry
country: United Kingdom
facility: Walsgrave Hospital
state: England
city: Derby
country: United Kingdom
facility: Derbyshire Royal Infirmary
state: England
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
state: England
city: Guildford
country: United Kingdom
facility: St. Luke's Cancer Centre at Royal Surrey County Hospital
state: England
city: Hull
country: United Kingdom
facility: Princess Royal Hospital at Hull and East Yorkshire NHS Trust
state: England
city: London
country: United Kingdom
facility: St. Thomas' Hospital
state: England
city: Maidstone
country: United Kingdom
facility: Maidstone Hospital
state: England
city: Merseyside
country: United Kingdom
facility: Clatterbridge Centre for Oncology
state: England
city: Middlesbrough
country: United Kingdom
facility: James Cook University Hospital
state: England
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Northern Centre for Cancer Treatment at Newcastle General Hospital
state: England
city: Northampton
country: United Kingdom
facility: Northampton General Hospital NHS Trust
state: England
city: Shrewsbury
country: United Kingdom
facility: Royal Shrewsbury Hospital
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust - Surrey
state: England
city: Torquay
country: United Kingdom
facility: Torbay Hospital
state: England
city: West Midlands
country: United Kingdom
facility: Good Hope Hospital Trust
state: England
city: Westcliff-On-Sea
country: United Kingdom
facility: Southend University Hospital NHS Foundation Trust
state: England
city: Worthing
country: United Kingdom
facility: Worthing Hospital
state: England
city: Yeovil
country: United Kingdom
facility: Yeovil District Hospital
state: England
city: Rhyl
country: United Kingdom
facility: Glan Clwyd Hospital
state: Wales
Study officials:
affiliation: University Hospital Birmingham
name: Nicholas D. James, MD
role: STUDY_CHAIR
References:
citation: 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. 2012 Apr 19;366(16):1477-88. doi: 10.1056/NEJMoa1106106.
citation: Choudhury A, Porta N, Hall E, Song YP, Owen R, MacKay R, West CML, Lewis R, Hussain SA, James ND, Huddart R, Hoskin P; BC2001 and BCON investigators. Hypofractionated radiotherapy in locally advanced bladder cancer: an individual patient data meta-analysis of the BC2001 and BCON trials. Lancet Oncol. 2021 Feb;22(2):246-255. doi: 10.1016/S1470-2045(20)30607-0.