Efficacy Study of Adding Chemotherapy to Radiotherapy for Treating Bladder Cancer. - Full Text View

Sponsors and Collaborators:	Trans-Tasman Radiation Oncology Group (TROG) National Health and Medical Research Council, Australia
Information provided by:	Trans-Tasman Radiation Oncology Group (TROG)
ClinicalTrials.gov Identifier:	NCT00330499

Purpose

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.

Condition	Intervention	Phase
Transitional Cell Carcinoma of Urinary Bladder	Drug: Cisplatin Radiation: External beam radiation treatment	Phase III

Genetics Home Reference related topics: bladder cancer

MedlinePlus related topics: Bladder Cancer Cancer

Drug Information available for: Cisplatin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
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

Further study details as provided by Trans-Tasman Radiation Oncology Group (TROG):

Primary Outcome Measures:

Invasive local failure at 3 years [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Complete response (CR) rate at 3 months from randomisation [ Time Frame: 3 months ] [ Designated as safety issue: No ]
Disease-free survival [ Time Frame: Final analysis when all patients have been followed for 3 years. (approx. 7 years from start of trial) ] [ Designated as safety issue: No ]
Overall survival [ Time Frame: Final analysis when all patients have been followed for 3 years. (approx. 7 years from start of trial) ] [ Designated as safety issue: No ]
Cystectomy-free survival [ Time Frame: Final analysis when all patients have been followed for 3 years. (approx. 7 years from start of trial) ] [ Designated as safety issue: No ]
Acute and late toxicity [ Time Frame: Interim analyses will be performed on an annual basis. ] [ Designated as safety issue: Yes ]
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) ] [ Designated as safety issue: No ]
Quality of life measures [ Time Frame: Final analysis when all patients have been followed for 3 years. (approx. 7 years from start of trial) ] [ Designated as safety issue: No ]

Estimated Enrollment:	150
Study Start Date:	October 2002
Estimated Study Completion Date:	December 2011
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental Synchronous chemo / radiation therapy	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
B: Active Comparator Radiation Alone	Radiation: External beam radiation treatment 64Gy reference dose in 32 fractions over 6.5 weeks

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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:
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00330499

Locations

Australia, New South Wales
Liverpool Hospital
Liverpool, New South Wales, Australia, 1871
Nepean Cancer Care Centre
Penrith, New South Wales, Australia, 2751
Calvary Mater Newcastle
Newcastle, New South Wales, Australia, 2298
Prince of Wales Hospital
Randwick, New South Wales, Australia, 2031
Westmead Hospital
Wentworthville, New South Wales, Australia, 2145
Australia, Queensland
Mater Centre - South Brisbane
Brisbane, Queensland, Australia, 4120
East Coast Cancer Centre
Tugun, Queensland, Australia, 4224
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia, 4102
Royal Brisbane Hospital
Herston, Queensland, Australia, 4029
Townsville Hospital
Douglas, Queensland, Australia, 4814
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
Australia, Tasmania
Launceston General Hospital
Launceston, Tasmania, Australia, 7250
Australia, Victoria
Alfred Hospital
Prahran, Victoria, Australia, 3181
Andrew Love Cancer Care Centre, Geelong Hospital
Geelong, Victoria, Australia, 3220
Peter MacCallum Cancer Centre
East Melbourne, Victoria, Australia, 3002
Australia, Western Australia
Royal Perth Hospital
Perth, Western Australia, Australia, 6000
Sir Charles Gairdner Hospital
Nedlands, Western Australia, Australia, 6009
New Zealand
Wellington Hospital
Wellington, New Zealand, 7902
Christchurch Hospital
Christchurch, New Zealand, 4710
Dunedin Hospital
Dunedin, New Zealand
Palmerston North Hospital
Palmerston North, New Zealand
Auckland Hospital
Auckland, New Zealand, 1001

Sponsors and Collaborators

Trans-Tasman Radiation Oncology Group (TROG)

National Health and Medical Research Council, Australia

Investigators

Study Chair:

Kumar Gogna

Mater Centre - South Brisbane

More Information

Click here for more information about this study on the TROG official website This link exits the ClinicalTrials.gov site

Responsible Party:	Trans Tasman Radiation Oncology Group ( Dr Kumar Gogna )
Study ID Numbers:	TROG 02.03, NHMRC 243100
Study First Received:	May 25, 2006
Last Updated:	October 22, 2008
ClinicalTrials.gov Identifier:	NCT00330499
Health Authority:	Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Trans-Tasman Radiation Oncology Group (TROG):

Locally invasive
Bladder cancer
Chemoradiotherapy
Efficacy
Organ conservation

Study placed in the following topic categories:

Cystocele
Urinary Bladder Diseases
Urinary Bladder Neoplasms
Urogenital Neoplasms
Carcinoma, Transitional Cell
Urologic Neoplasms
Transitional cell carcinoma

Carcinoma
Urologic Diseases
Cisplatin
Urinary tract neoplasm
Neoplasms, Glandular and Epithelial
Bladder neoplasm

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Radiation-Sensitizing Agents

Antineoplastic Agents
Therapeutic Uses
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009