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

January 2, 2019 updated by: Institute of Cancer Research, United Kingdom

Randomised Trial of Selective Bladder Preservation Against Radical Excision (Cystectomy) in Muscle Invasive T2/T3 Transitional Cell Carcinoma of the Bladder - Feasibility Study

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

45

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • England
      • Sutton, England, United Kingdom, SM2 5PT
        • Institute of Cancer Research - Sutton

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed transitional cell carcinoma (TCC) of the bladder

    • Clinical stage T2-T3, N0, M0
  • No widespread carcinoma in situ (CIS) or CIS remote from muscle invasive tumor

  • No adenocarcinoma, squamous cell carcinoma (SCC), small cell carcinoma, or other variant histology

    • N.B. squamoid differentiation or mixed TCC/SCC allowed

  • No simultaneous upper tract, urethral, or prostatic urethral TCC

    • Direct prostatic urethral extension from bladder primary allowed if not involving prostatic stroma
  • Currently receiving 3 courses of gemcitabine hydrochloride-cisplatin or other protocol approved neoadjuvant chemotherapy regimen AND willing and fit to receive a 4th course according to study protocol

PATIENT CHARACTERISTICS:

  • WHO performance status 0-1
  • Hemoglobin > 10 g/dL
  • WBC > 3,000/mm³
  • Platelet count > 150,000/mm³
  • Bilirubin < 1.5 times upper limit of normal (ULN)
  • AST < 1.5 times ULN
  • Alkaline phosphatase < 1.5 times ULN
  • Not pregnant
  • Fit for radical cystectomy or radical radiotherapy
  • No prior malignancy within the past 5 years except superficial TCC or CIS

  • No untreated hydronephrosis

    • Patients with hydronephrosis are eligible if the kidney/ureter has been stented or nephrostomy has been inserted and renal function has been maintained
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arm I

Patients undergo a radical cystectomy, including pelvic lymphadenectomy,

between 4 and 6 weeks after initiating course 4 of chemotherapy.
Procedure: therapeutic conventional surgery
Patients undergo radical cystectomy
Experimental: 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.
Radiation: radiation therapy
Patients undergo radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Overall survival
Number of patients randomized over 3 years
Proportion of patients undergoing selective bladder preservation
Proportion of patients undergoing radical cystectomy

Secondary Outcome Measures

Outcome Measure
Toxicity as assessed by NCI CTCAE v3.0
Compliance with randomized treatment
Rate of salvage cystectomy after selective bladder preservation
Quality of life as assessed by the QLQ-C30 v3.0 questionnaire
Locoregional progression-free, metastasis-free, and overall survival

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institute of Cancer Research, United Kingdom

Investigators

  • Principal Investigator: Robert A. Huddart, MD, Royal Marsden NHS Foundation Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2007

Primary Completion (Actual)

February 1, 2010

Study Completion (Actual)

April 1, 2017

Study Registration Dates

First Submitted

March 20, 2009

First Submitted That Met QC Criteria

March 20, 2009

First Posted (Estimate)

March 23, 2009

Study Record Updates

Last Update Posted (Actual)

January 4, 2019

Last Update Submitted That Met QC Criteria

January 2, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000633526
  • ICR-SPARE
  • ISRCTN61126465
  • EU-20907
  • ICR-CTSU/2006/10002

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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