A Randomised Trial of Radical Chemo/Radiotherapy vs Radiotherapy Alone in the Definitive Management of Localised Muscle Invasive TCC of the Urinary Bladder
18 Years
N/A
Both
Transitional Cell Carcinoma of Urinary Bladder
Trial Information
A Randomised Trial of Radical Chemo/Radiotherapy vs Radiotherapy Alone in the Definitive Management of Localised Muscle Invasive TCC of the Urinary Bladder
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).
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:
1. partial cystectomy;
2. endoscopic resection of bladder tumour/s;
3. intravesical chemotherapy; or
4. 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:
1. non-melanoma skin cancer, and/or
2. (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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Invasive local failure at 3 years
Outcome Time Frame:
3 years
Safety Issue:
No
Principal Investigator
Kumar Gogna
Investigator Role:
Study Chair
Investigator Affiliation:
Mater Centre - South Brisbane
Authority:
Australia: Department of Health and Ageing Therapeutic Goods Administration
Study ID:
TROG 02.03
NCT ID:
NCT00330499
Start Date:
October 2002
Completion Date:
November 2010
Related Keywords:
- Transitional Cell Carcinoma of Urinary Bladder
- Locally invasive
- Bladder cancer
- Chemoradiotherapy
- Efficacy
- Organ conservation
- Urinary Bladder Neoplasms
- Carcinoma
- Carcinoma, Transitional Cell
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