Back to resultsEfficacy Study of Adding Chemotherapy to Radiotherapy for Treating Bladder Cancer.
Primary Purpose
Transitional Cell Carcinoma of Urinary Bladder
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Cisplatin
External beam radiation treatment
Sponsored by
About this trial
This is an interventional treatment trial for Transitional Cell Carcinoma of Urinary Bladder focused on measuring Locally invasive, Bladder cancer, Chemoradiotherapy, Efficacy, Organ conservation
Eligibility Criteria
Inclusion Criteria: Histologically proven TCC of the urinary bladder. Mixed tumours comprising predominantly TCC and elements of squamous or adenomatous metaplasia or carcinoma are also eligible. Clinically and radiologically localised T2, T3 or T4a non-bulky disease (<= 7cm in maximum dimension), N0, M0. If radiological evaluation of a lymph node is interpreted as "positive" this must be evaluated further by either lymph node sampling or percutaneous needle biopsy. Patients with histologically confirmed lymph node metastases will not be eligible. Maximal TUR. N.B. Previous: partial cystectomy; endoscopic resection of bladder tumour/s; intravesical chemotherapy; or intravesical BCG does not exclude the patient from being eligible. However, the patient should have an adequate functioning bladder (this should be clarified with the referring Urologist and if need be voiding volumes should be measured). Creatinine clearance >= 50ml/minute by calculation or measurement. A white blood cell count >= 3.5 x 10^9/L with an absolute neutrophil count >= 1.5 x 10^9/L and a platelet count >= 100 x 10^9/L. ECOG status of 0, 1 or 2. No age limit applies provided the patient is mentally, physically and geographically capable of undergoing treatment and follow-up. No significant intercurrent morbidity. Exclusion Criteria: Pure squamous carcinomas or adenocarcinomas. Extensive or multifocal CIS change in the bladder. T3 or T4a tumours unsuitable for curative treatment (i.e. > 7cm in any dimension), T4b, node positive and metastatic disease. Presence of ureteric obstruction due to tumour infiltration at the UO not amenable to stenting. Previous radiation treatment to the pelvis. Previous significant pelvic surgery. Significant bowel or gynaecological inflammatory disease. Creatinine clearance < 50ml/minute by calculation or measurement. A white blood cell count < 3.5 x 10^9/L with an absolute neutrophil count < 1.5 x 10^9L and/or a platelet count < 100 x 10^9/L. Other considerations making patient unfit for Cisplatin therapy. Prior or concurrent malignancy of any other site unless disease-free for greater than 5 years, except for: non-melanoma skin cancer, and/or (a) Stage T1 well differentiated prostatic carcinoma in men, and In situ carcinoma of the cervix in women. Bladder tumour - biopsy only. These patients must be referred back for more adequate resections or else should not be included
Sites / Locations
- Liverpool Hospital
- Calvary Mater Newcastle
- Nepean Cancer Care Centre
- Prince of Wales Hospital
- Westmead Hospital
- Mater Centre - South Brisbane
- Townsville Hospital
- Royal Brisbane Hospital
- East Coast Cancer Centre
- Princess Alexandra Hospital
- Royal Adelaide Hospital
- Launceston General Hospital
- Peter MacCallum Cancer Centre
- Andrew Love Cancer Care Centre, Geelong Hospital
- Alfred Hospital
- Sir Charles Gairdner Hospital
- Royal Perth Hospital
- Auckland Hospital
- Christchurch Hospital
- Dunedin Hospital
- Palmerston North Hospital
- Wellington Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
A
B
Arm Description
Synchronous chemo / radiation therapy
Radiation Alone
Outcomes
Primary Outcome Measures
Invasive local failure at 3 years
Secondary Outcome Measures
Complete response (CR) rate at 3 months from randomisation
Disease-free survival
Overall survival
Cystectomy-free survival
Acute and late toxicity
Pattern of failure (local, regional, distant)
Quality of life measures
Full Information
NCT ID
NCT00330499
First Posted
May 25, 2006
Last Updated
July 10, 2017
Sponsor
Trans Tasman Radiation Oncology Group
Collaborators
National Health and Medical Research Council, Australia
1. Study Identification
Unique Protocol Identification Number
NCT00330499
Brief Title
Efficacy Study of Adding Chemotherapy to Radiotherapy for Treating Bladder Cancer.
Official Title
A Randomised Trial of Radical Chemo/Radiotherapy vs Radiotherapy Alone in the Definitive Management of Localised Muscle Invasive TCC of the Urinary Bladder
Study Type
Interventional
2. Study Status
Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
October 2002 (undefined)
Primary Completion Date
February 2010 (Actual)
Study Completion Date
February 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Trans Tasman Radiation Oncology Group
Collaborators
National Health and Medical Research Council, Australia
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to define the optimal management of localised transitional cell carcinoma (TCC) of the urinary bladder. The main objective is to evaluate whether chemoradiation is superior to radiotherapy alone.
Detailed Description
Whilst concurrent chemo-radiation is increasingly being looked upon as the treatment of choice for patients referred for bladder preservation, the study by the NCI of Canada (Coppin CM, Gospodarowicz MK et al.Improved Local Control of Invasive Bladder Cancer by Concurrent Cisplatin and Pre-operative or Definitive Radiation.J. of Clinical Oncol. 14(11): 2901-2907, 1996) is the only randomised trial to show some superiority of concurrent Cisplatin and radiation treatment over radiation alone in increasing pelvic tumour control. There was no impact on overall survival. However, this study had relatively small subject numbers and included two distinct treatment options. In one group the patients were treated with a bladder sparing approach and in the other by pre-operative therapy and cystectomy with the type of definitive treatment being decided upon by both the treating Specialist and patient. At 5 years the pelvic failure rates in the radiation alone and chemo-radiation arms were 59% and 40% respectively. With half of the patients in each group having had planned cystectomy as part of their treatment regimen, the above rates of local relapse (especially in the chemo-radiation arm) are disappointing.
Given the concerns with the above study, and the continuing paucity of randomised phase III studies comparing chemo-radiation with radiation alone, there lies an opportunity for Australasian centres to take up the challenge. For this study, the proposed schedule for the chemo-radiation arm is to be the same as that being investigated in our previous phase II study (six weekly doses of Cisplatin plus radiation to a dose of 64Gy in 32 fractions over 6.5 weeks). This will be compared with radical radiation alone (64Gy in 32 fractions over 6.5 weeks).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Transitional Cell Carcinoma of Urinary Bladder
Keywords
Locally invasive, Bladder cancer, Chemoradiotherapy, Efficacy, Organ conservation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
67 (Actual)
8. Arms, Groups, and Interventions
Arm Title
A
Arm Type
Experimental
Arm Description
Synchronous chemo / radiation therapy
Arm Title
B
Arm Type
Active Comparator
Arm Description
Radiation Alone
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
Cisplatuin Ebewe, Cisplatin Injection
Intervention Description
Weekly Cisplatin 35mg/m2 x 6 doses, IV administration
Intervention Type
Radiation
Intervention Name(s)
External beam radiation treatment
Other Intervention Name(s)
Radiation
Intervention Description
64Gy reference dose in 32 fractions over 6.5 weeks
Primary Outcome Measure Information:
Title
Invasive local failure at 3 years
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Complete response (CR) rate at 3 months from randomisation
Time Frame
3 months
Title
Disease-free survival
Time Frame
Final analysis when all patients have been followed for 3 years. (approx. 7 years from start of trial)
Title
Overall survival
Time Frame
Final analysis when all patients have been followed for 3 years. (approx. 7 years from start of trial)
Title
Cystectomy-free survival
Time Frame
Final analysis when all patients have been followed for 3 years. (approx. 7 years from start of trial)
Title
Acute and late toxicity
Time Frame
Interim analyses will be performed on an annual basis.
Title
Pattern of failure (local, regional, distant)
Time Frame
Final analysis when all patients have been followed for 3 years. (approx. 7 years from start of trial)
Title
Quality of life measures
Time Frame
Final analysis when all patients have been followed for 3 years. (approx. 7 years from start of trial)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically proven TCC of the urinary bladder. Mixed tumours comprising predominantly TCC and elements of squamous or adenomatous metaplasia or carcinoma are also eligible.
Clinically and radiologically localised T2, T3 or T4a non-bulky disease (<= 7cm in maximum dimension), N0, M0.
If radiological evaluation of a lymph node is interpreted as "positive" this must be evaluated further by either lymph node sampling or percutaneous needle biopsy. Patients with histologically confirmed lymph node metastases will not be eligible.
Maximal TUR.
N.B. Previous:
partial cystectomy;
endoscopic resection of bladder tumour/s;
intravesical chemotherapy; or
intravesical BCG
does not exclude the patient from being eligible. However, the patient should have an adequate functioning bladder (this should be clarified with the referring Urologist and if need be voiding volumes should be measured).
Creatinine clearance >= 50ml/minute by calculation or measurement.
A white blood cell count >= 3.5 x 10^9/L with an absolute neutrophil count >= 1.5 x 10^9/L and a platelet count >= 100 x 10^9/L.
ECOG status of 0, 1 or 2.
No age limit applies provided the patient is mentally, physically and geographically capable of undergoing treatment and follow-up.
No significant intercurrent morbidity.
Exclusion Criteria:
Pure squamous carcinomas or adenocarcinomas.
Extensive or multifocal CIS change in the bladder.
T3 or T4a tumours unsuitable for curative treatment (i.e. > 7cm in any dimension), T4b, node positive and metastatic disease.
Presence of ureteric obstruction due to tumour infiltration at the UO not amenable to stenting.
Previous radiation treatment to the pelvis.
Previous significant pelvic surgery.
Significant bowel or gynaecological inflammatory disease.
Creatinine clearance < 50ml/minute by calculation or measurement. A white blood cell count < 3.5 x 10^9/L with an absolute neutrophil count < 1.5 x 10^9L and/or a platelet count < 100 x 10^9/L.
Other considerations making patient unfit for Cisplatin therapy.
Prior or concurrent malignancy of any other site unless disease-free for greater than 5 years, except for:
non-melanoma skin cancer, and/or
(a) Stage T1 well differentiated prostatic carcinoma in men, and In situ carcinoma of the cervix in women.
Bladder tumour - biopsy only. These patients must be referred back for more adequate resections or else should not be included
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kumar Gogna
Organizational Affiliation
Mater Centre - South Brisbane
Official's Role
Study Chair
Facility Information:
Facility Name
Liverpool Hospital
City
Liverpool
State/Province
New South Wales
ZIP/Postal Code
1871
Country
Australia
Facility Name
Calvary Mater Newcastle
City
Newcastle
State/Province
New South Wales
ZIP/Postal Code
2298
Country
Australia
Facility Name
Nepean Cancer Care Centre
City
Penrith
State/Province
New South Wales
ZIP/Postal Code
2751
Country
Australia
Facility Name
Prince of Wales Hospital
City
Randwick
State/Province
New South Wales
ZIP/Postal Code
2031
Country
Australia
Facility Name
Westmead Hospital
City
Wentworthville
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Mater Centre - South Brisbane
City
Brisbane
State/Province
Queensland
ZIP/Postal Code
4120
Country
Australia
Facility Name
Townsville Hospital
City
Douglas
State/Province
Queensland
ZIP/Postal Code
4814
Country
Australia
Facility Name
Royal Brisbane Hospital
City
Herston
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Facility Name
East Coast Cancer Centre
City
Tugun
State/Province
Queensland
ZIP/Postal Code
4224
Country
Australia
Facility Name
Princess Alexandra Hospital
City
Woolloongabba
State/Province
Queensland
ZIP/Postal Code
4102
Country
Australia
Facility Name
Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
Launceston General Hospital
City
Launceston
State/Province
Tasmania
ZIP/Postal Code
7250
Country
Australia
Facility Name
Peter MacCallum Cancer Centre
City
East Melbourne
State/Province
Victoria
ZIP/Postal Code
3002
Country
Australia
Facility Name
Andrew Love Cancer Care Centre, Geelong Hospital
City
Geelong
State/Province
Victoria
ZIP/Postal Code
3220
Country
Australia
Facility Name
Alfred Hospital
City
Prahran
State/Province
Victoria
ZIP/Postal Code
3181
Country
Australia
Facility Name
Sir Charles Gairdner Hospital
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
Royal Perth Hospital
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6000
Country
Australia
Facility Name
Auckland Hospital
City
Auckland
ZIP/Postal Code
1001
Country
New Zealand
Facility Name
Christchurch Hospital
City
Christchurch
ZIP/Postal Code
4710
Country
New Zealand
Facility Name
Dunedin Hospital
City
Dunedin
Country
New Zealand
Facility Name
Palmerston North Hospital
City
Palmerston North
Country
New Zealand
Facility Name
Wellington Hospital
City
Wellington
ZIP/Postal Code
7902
Country
New Zealand
12. IPD Sharing Statement
Links:
URL
http://www.trog.com.au
Description
Click here for more information about this study on the TROG official website
Learn more about this trial
Efficacy Study of Adding Chemotherapy to Radiotherapy for Treating Bladder Cancer.
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