Clinical trial NCT00330499: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Transitional Cell Carcinoma of Urinary Bladder
Keywords: Locally invasive
Bladder cancer
Chemoradiotherapy
Efficacy
Organ conservation
Lead sponsor: Trans Tasman Radiation Oncology Group
Sponsor class: OTHER
Collaborators: name: National Health and Medical Research Council, Australia
First posted: 2006-05-26
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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:

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

Primary outcomes:
measure: Invasive local failure at 3 years
timeFrame: 3 years
Secondary outcomes:
measure: Complete response (CR) rate at 3 months from randomisation
timeFrame: 3 months
measure: Disease-free survival
timeFrame: Final analysis when all patients have been followed for 3 years. (approx. 7 years from start of trial)
measure: Overall survival
timeFrame: Final analysis when all patients have been followed for 3 years. (approx. 7 years from start of trial)
measure: Cystectomy-free survival
timeFrame: Final analysis when all patients have been followed for 3 years. (approx. 7 years from start of trial)
measure: Acute and late toxicity
timeFrame: Interim analyses will be performed on an annual basis.
measure: Pattern of failure (local, regional, distant)
timeFrame: Final analysis when all patients have been followed for 3 years. (approx. 7 years from start of trial)
measure: Quality of life measures
timeFrame: Final analysis when all patients have been followed for 3 years. (approx. 7 years from start of trial)
Other outcomes:
Locations:
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Newcastle
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Penrith
country: Australia
facility: Nepean Cancer Care Centre
state: New South Wales
city: Randwick
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Wentworthville
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Mater Centre - South Brisbane
state: Queensland
city: Douglas
country: Australia
facility: Townsville Hospital
state: Queensland
city: Herston
country: Australia
facility: Royal Brisbane Hospital
state: Queensland
city: Tugun
country: Australia
facility: East Coast Cancer Centre
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Launceston
country: Australia
facility: Launceston General Hospital
state: Tasmania
city: East Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Geelong
country: Australia
facility: Andrew Love Cancer Care Centre, Geelong Hospital
state: Victoria
city: Prahran
country: Australia
facility: Alfred Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Auckland
country: New Zealand
facility: Auckland Hospital
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Dunedin
country: New Zealand
facility: Dunedin Hospital
city: Palmerston North
country: New Zealand
facility: Palmerston North Hospital
city: Wellington
country: New Zealand
facility: Wellington Hospital
Study officials:
affiliation: Mater Centre - South Brisbane
name: Kumar Gogna
role: STUDY_CHAIR
References: