Efficacy Study of Adding Chemotherapy to Radiotherapy for Treating Bladder Cancer.

Transitional Cell Carcinoma of Urinary Bladder Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00330499
• Other study ID #: TROG 02.03
• Secondary ID: NHMRC 243100
• Status: Completed
• Phase: Phase 3
• First received: May 25, 2006
• Last updated: July 10, 2017
• Start date: October 2002
• Est. completion date: February 2010

Study information

• Verified date: July 2017
• Source: Trans-Tasman Radiation Oncology Group (TROG)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 67
• Est. completion date: February 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Transitional Cell
• Transitional Cell Carcinoma of Urinary Bladder
• Urinary Bladder Neoplasms

Intervention

Drug:
• Cisplatin
Weekly Cisplatin 35mg/m2 x 6 doses, IV administration

Radiation:
• External beam radiation treatment
64Gy reference dose in 32 fractions over 6.5 weeks

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Mater Centre - South Brisbane	Brisbane	Queensland
Australia	Townsville Hospital	Douglas	Queensland
Australia	Peter MacCallum Cancer Centre	East Melbourne	Victoria
Australia	Andrew Love Cancer Care Centre, Geelong Hospital	Geelong	Victoria
Australia	Royal Brisbane Hospital	Herston	Queensland
Australia	Launceston General Hospital	Launceston	Tasmania
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Australia	Calvary Mater Newcastle	Newcastle	New South Wales
Australia	Nepean Cancer Care Centre	Penrith	New South Wales
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	Alfred Hospital	Prahran	Victoria
Australia	Prince of Wales Hospital	Randwick	New South Wales
Australia	East Coast Cancer Centre	Tugun	Queensland
Australia	Westmead Hospital	Wentworthville	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
New Zealand	Auckland Hospital	Auckland
New Zealand	Christchurch Hospital	Christchurch
New Zealand	Dunedin Hospital	Dunedin
New Zealand	Palmerston North Hospital	Palmerston North
New Zealand	Wellington Hospital	Wellington

Sponsors (2)

Lead Sponsor	Collaborator
Trans-Tasman Radiation Oncology Group (TROG)	National Health and Medical Research Council, Australia

Countries where clinical trial is conducted

Australia,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Invasive local failure at 3 years		3 years
Secondary	Complete response (CR) rate at 3 months from randomisation		3 months
Secondary	Disease-free survival		Final analysis when all patients have been followed for 3 years. (approx. 7 years from start of trial)
Secondary	Overall survival		Final analysis when all patients have been followed for 3 years. (approx. 7 years from start of trial)
Secondary	Cystectomy-free survival		Final analysis when all patients have been followed for 3 years. (approx. 7 years from start of trial)
Secondary	Acute and late toxicity		Interim analyses will be performed on an annual basis.
Secondary	Pattern of failure (local, regional, distant)		Final analysis when all patients have been followed for 3 years. (approx. 7 years from start of trial)
Secondary	Quality of life measures		Final analysis when all patients have been followed for 3 years. (approx. 7 years from start of trial)

External Links

•   Click here for more information about this study on the TROG official website