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

Phase 3

Completed

• Conditions: Transitional Cell Carcinoma of Urinary Bladder
• Interventions: Drug: Cisplatin; Radiation: External beam radiation treatment

• Registration Number: NCT00330499
• Lead Sponsor: Trans Tasman Radiation Oncology Group

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).

Study Timeline

• Study Start: 2002-10
• Study First Submitted: 2006-05-25
• Study First Submitted QC: 2006-05-25
• Study First Posted: 2006-05-26
• Primary Completion: 2010-02
• Study Completion: 2010-02
• Status Verified: 2017-07
• Last Update Submitted: 2017-07-10
• Last Update Posted: 2017-07-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 67

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A	Cisplatin	Synchronous chemo / radiation therapy
A	External beam radiation treatment	Synchronous chemo / radiation therapy
B	External beam radiation treatment	Radiation Alone

Primary Outcome Measures

Name	Time	Method
Invasive local failure at 3 years	3 years

Secondary Outcome Measures

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

Trial Locations

Locations (22)

Liverpool Hospital; 🇦🇺 Liverpool, New South Wales, Australia

Calvary Mater Newcastle; 🇦🇺 Newcastle, New South Wales, Australia

Nepean Cancer Care Centre; 🇦🇺 Penrith, New South Wales, Australia

Prince of Wales Hospital; 🇦🇺 Randwick, New South Wales, Australia

Westmead Hospital; 🇦🇺 Wentworthville, New South Wales, Australia

Mater Centre - South Brisbane; 🇦🇺 Brisbane, Queensland, Australia

Townsville Hospital; 🇦🇺 Douglas, Queensland, Australia

Royal Brisbane Hospital; 🇦🇺 Herston, Queensland, Australia

East Coast Cancer Centre; 🇦🇺 Tugun, Queensland, Australia

Princess Alexandra Hospital; 🇦🇺 Woolloongabba, Queensland, Australia

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