Radiation Therapy or Surgery in Treating Patients Receiving Chemotherapy for Bladder Cancer

NCT ID: NCT00867347

Last Updated: 2019-01-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-31
• Study Completion Date: 2017-04-30

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as gemcitabine and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Radiation therapy uses high-energy x-rays to kill tumor cells. It is not yet known whether radiation therapy is more effective than surgery in treating patients with bladder cancer.

PURPOSE: This randomized phase III trial is studying radiation therapy to see how well it works compared with surgery in treating patients with bladder cancer who are receiving chemotherapy.

Detailed Description

OBJECTIVES:

Primary

• To determine the feasibility and patient acceptability of radical cystectomy vs selective bladder preservation (SBP) after neoadjuvant chemotherapy in patients with muscle-invasive transitional cell carcinoma of the bladder.
• To determine compliance rates of patients with their assigned treatments.
• To determine if bladder preservation is equivalent to radical cystectomy, in terms of overall survival, in responders to neoadjuvant chemotherapy.

Secondary

• To compare the overall survival of patients receiving SBP vs radical cystectomy.
• To determine the rate of salvage cystectomy in patients undergoing bladder preservation.
• To determine and compare the toxicity of treatment in both arms.
• To determine and compare quality of life of patients treated with these regimens.
• To compare locoregional progression-free and metastasis-free survival of patients treated with these regimens.

OUTLINE: This is a multicenter study. Patients are stratified according to cancer center and randomized to 1 of 2 treatment arms. Patients are assessed after completion of 3 courses of pre-study neoadjuvant chemotherapy. Patients with poor response (≥ pT2, residual pT2, macroscopic invasive tumor) undergo immediate radical cystectomy (within 6 weeks fo completing chemotherapy). Patients* with responsive disease (≤ pT1 tumor or macroscopically normal bladder) proceed to course 4 of chemotherapy (on-study) followed by treatment according to randomization arm.

NOTE: *Patients with a clear bladder or those who are unsure of their histological results prior to course 4 also proceed to chemotherapy.

• Course 4 of neoadjuvant chemotherapy: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and cisplatin IV over 4 hours on day 1.
• Arm I (radical cystectomy): Patients undergo a radical cystectomy, including pelvic lymphadenectomy, between 4 and 6 weeks after initiating course 4 of chemotherapy.
• Arm II (selective bladder preservation): Patients with no visible residual tumor (cT0 or pT0) or residual but superficial tumor (pTa, pT1) undergo radiotherapy beginning within 4-6 weeks of day 1 of course 4 and continuing for 6.5 weeks.

Health-related quality of life is assessed periodically.

After completion of study treatment, patients are followed periodically for up to 5 years.

Conditions

Bladder Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

Patients undergo a radical cystectomy, including pelvic lymphadenectomy,

between 4 and 6 weeks after initiating course 4 of chemotherapy.

Group Type: ACTIVE_COMPARATOR

therapeutic conventional surgery

Intervention Type: PROCEDURE

Patients undergo radical cystectomy

Arm II

Patients with no visible residual tumor (cT0 or pT0) or residual but superficial tumor (pTa, pT1) undergo radiotherapy beginning within 4-6 weeks of day 1 of course 4 and continuing for 6.5 weeks.

Group Type: EXPERIMENTAL

radiation therapy

Intervention Type: RADIATION

Patients undergo radiotherapy

Interventions

therapeutic conventional surgery

Patients undergo radical cystectomy

Intervention Type: PROCEDURE

radiation therapy

Patients undergo radiotherapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• No contraindication to radical radiotherapy (e.g., inflammatory bowel disease, radiosensitivity syndrome, or severe diverticular disease)
• No bilateral total hip replacements
• No significant comorbid medical conditions that would interfere with administration of any protocol treatment

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior pelvic radiotherapy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institute of Cancer Research, United Kingdom

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert A. Huddart, MD

Role: PRINCIPAL_INVESTIGATOR

Royal Marsden NHS Foundation Trust

Locations

Institute of Cancer Research - Sutton

Sutton, England, United Kingdom

Countries

United Kingdom

References

Paramasivan S, Huddart R, Hall E, Lewis R, Birtle A, Donovan JL. Key issues in recruitment to randomised controlled trials with very different interventions: a qualitative investigation of recruitment to the SPARE trial (CRUK/07/011). Trials. 2011 Mar 15;12:78. doi: 10.1186/1745-6215-12-78.

Reference Type: RESULT

PMID: 21406089 (View on PubMed)

Huddart RA, Birtle A, Maynard L, Beresford M, Blazeby J, Donovan J, Kelly JD, Kirkbank T, McLaren DB, Mead G, Moynihan C, Persad R, Scrase C, Lewis R, Hall E. Clinical and patient-reported outcomes of SPARE - a randomised feasibility study of selective bladder preservation versus radical cystectomy. BJU Int. 2017 Nov;120(5):639-650. doi: 10.1111/bju.13900. Epub 2017 May 29.

Reference Type: RESULT

PMID: 28453896 (View on PubMed)

Other Identifiers

ICR-SPARE

Identifier Type: -

Identifier Source: secondary_id

ISRCTN61126465

Identifier Type: -

Identifier Source: secondary_id

EU-20907

Identifier Type: -

Identifier Source: secondary_id

ICR-CTSU/2006/10002

Identifier Type: -

Identifier Source: secondary_id

CDR0000633526

Identifier Type: -

Identifier Source: org_study_id