Clinical trial NCT00002990: Surgery and BCG in Treating Patients With Bladder Cancer
Official title: Comparative Study of Intravesical BCG Standard Dose Long-Term Maintenance Versus BCG 1/3 Dose Long-Term Maintenance Versus BCG Standard Dose Short-Term Maintenance Versus BCG 1/3 Dose Short-Term Maintenance in Intermediate and High Risk Ta, T1 Papillary Carcinoma of the Urinary Bladder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bladder Cancer
Keywords: stage 0 bladder cancer
stage I bladder cancer
transitional cell carcinoma of the bladder
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2003-01-27
Enrollment: 1288
Sex: ALL
Maximum age (years): 85
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Biological therapies such as BCG use different ways to stimulate the immune system and stop cancer cells from growing.

PURPOSE: This randomized phase III trial is studying four different regimens of BCG and comparing how well they work in treating patients who have undergone surgery for bladder cancer.

Detailed description: OBJECTIVES:

* Demonstrate that after complete transurethral resection of all papillary tumors, one third dose BCG (Bacillus Calmette-Guerin vaccine; OncoTICE) is equivalent to full dose BCG and short term maintenance is equivalent to long term maintenance with respect to duration of disease free interval, recurrence rate, percentage of patients with an increase in T-category to greater than T1, and the incidence of carcinoma in situ during follow-up.
* Demonstrate that one third dose BCG and short term maintenance are associated with fewer local and systemic side effects.

OUTLINE: This is a prospective randomized study.

At 7-15 days after transurethral resection, patients will begin receiving one of the following four regimens:

* Regimen 1: One third dose Bacillus Calmette-Guerin (BCG) vaccine plus short term maintenance. Patients receive a one third dose of BCG instilled once a week for 6 weeks, followed by three weekly instillations at months 3, 6, and 12.
* Regimen 2: Full dose BCG plus short term maintenance. Patients receive a full dose of BCG instilled once a week for 6 weeks, followed by three weekly instillations at months 3, 6, and 12.
* Regimen 3: One third dose BCG plus long term maintenance. Patients receive a one third dose of BCG instilled once a week for 6 weeks, followed by three weekly instillations at months 3, 6, 12, 18, 24, 30 and 36.
* Regimen 4: Full dose BCG plus long term maintenance. Patients receive a full dose of BCG instilled once a week for 6 weeks, followed by three weekly instillations at months 3, 6, 12, 18, 24, 30, and 36.

The patient is followed every 3 months for the first 3 years, and every 6 months thereafter.

PROJECTED ACCRUAL: 1288 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed transitional cell carcinoma of the bladder of the following types:

  * Multiple (not greater than 10), resectable, T1 or Ta, grade G1-G3
  * Solitary T1 GIII tumor

PATIENT CHARACTERISTICS:

Age:

* 85 and under

Performance status:

* WHO 0-2

Life expectancy:

* Not specified

Hematopoietic:

* WBC at least 3,000/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic:

* Values used to evaluate function may not exceed two times the upper limit of normal

Renal:

* Values used to evaluate function may not exceed two times the upper limit of normal

Other:

* No second malignancy except basal cell skin carcinoma
* Not pregnant or nursing
* No uncontrollable urinary tract infection
* No active tuberculosis
* No HIV antibody
* No leukemia
* No Hodgkin's disease
* No transplant recipients

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No prior treatment with BCG

Chemotherapy:

* No cytostatic agents within the past 3 months

Endocrine therapy:

* Not specified

Radiotherapy:

* Not specified

Surgery:

* Not specified

Primary outcomes:
measure: Dose equivalency with respect to duration of disease free interval, recurrence rate, percentage of patients with an increase in T-category to greater than T1, and the incidence of carcinoma in situ during follow-up
measure: Dose equivalency in terms of fewer local and systemic side effects
Secondary outcomes:
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Kaiser Franz Josef Hospital
city: Aalst
country: Belgium
facility: Onze Lieve Vrouw Ziekenhuis Aalst
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Brussels
country: Belgium
facility: Academisch Ziekenhuis der Vrije Universiteit Brussel
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Ghent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Hasselt
country: Belgium
facility: Virga Jesse Hospital
city: Kortrijk
country: Belgium
facility: AZ Groeninge - Oncologisch Centrum
city: Lyon
country: France
facility: Hopital Edouard Herriot
city: Strasbourg
country: France
facility: Hopitaux Universitaire de Strasbourg
city: Ioannina
country: Greece
facility: G. Hatzikosta General Hospital
city: Rio Patras
country: Greece
facility: University of Patras Medical School
city: Petah-Tikva
country: Israel
facility: Rabin Medical Center - Beilinson Campus
city: Milano
country: Italy
facility: Istituto Scientifico H. San Raffaele
city: Milan
country: Italy
facility: Ospedale Di Desio
city: Novara
country: Italy
facility: Azienda Ospedaliera Maggiore Della Carita
city: Orbassano, (Torino)
country: Italy
facility: Azienda Ospedale S. Luigi - Universita Di Turin
city: Palermo
country: Italy
facility: Universita Di Palermo
city: Pisa
country: Italy
facility: Universita Degli Studi Di Pisa
city: Turin
country: Italy
facility: Azienda Sanitaria Ospedale San Giovanni Battista Molinette di Torino
city: Varese
country: Italy
facility: Ospedale di Circolo e Fondazione Macchi
city: 's-Hertogenbosch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gasthuis
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum
city: Breda
country: Netherlands
facility: Amphia Ziekenhuis - locatie Langendijk
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Leiderdorp
country: Netherlands
facility: Rijnland Ziekenhuis
city: Maastricht
country: Netherlands
facility: Academisch Ziekenhuis Maastricht
city: Nijmegen
country: Netherlands
facility: University Medical Center Nijmegen
city: Rotterdam
country: Netherlands
facility: University Medical Center Rotterdam at Erasmus Medical Center
city: Rotterdam
country: Netherlands
facility: St. Franciscus Gasthuis
city: Amadora
country: Portugal
facility: Hospital Desterro
city: Bucarest
country: Romania
facility: Institute of Oncology - Bucarest
city: Istanbul
country: Turkey
facility: Marmara University Hospital
city: Izmir
country: Turkey
facility: Dokuz Eylul University School of Medicine
city: Manisa
country: Turkey
facility: Celal Bayar University
city: Leeds
country: United Kingdom
facility: St. James's University Hospital at Leeds Teaching Hospital NHS Trust
state: England
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Freeman Hospital
state: England
city: Pontefract West Yorkshire
country: United Kingdom
facility: Pontefract General Infirmary
state: England
city: Glasgow
country: United Kingdom
facility: Gartnavel General Hospital
state: Scotland
Study officials:
affiliation: Jeroen Bosch Ziekenhuis
name: A. P.M. Van Der Meijden, MD, PhD
role: STUDY_CHAIR
References:
citation: Cambier S, Sylvester RJ, Collette L, Gontero P, Brausi MA, van Andel G, Kirkels WJ, Silva FC, Oosterlinck W, Prescott S, Kirkali Z, Powell PH, de Reijke TM, Turkeri L, Collette S, Oddens J. EORTC Nomograms and Risk Groups for Predicting Recurrence, Progression, and Disease-specific and Overall Survival in Non-Muscle-invasive Stage Ta-T1 Urothelial Bladder Cancer Patients Treated with 1-3 Years of Maintenance Bacillus Calmette-Guerin. Eur Urol. 2016 Jan;69(1):60-9. doi: 10.1016/j.eururo.2015.06.045. Epub 2015 Jul 23.
citation: Brausi M, Oddens J, Sylvester R, Bono A, van de Beek C, van Andel G, Gontero P, Turkeri L, Marreaud S, Collette S, Oosterlinck W. Side effects of Bacillus Calmette-Guerin (BCG) in the treatment of intermediate- and high-risk Ta, T1 papillary carcinoma of the bladder: results of the EORTC genito-urinary cancers group randomised phase 3 study comparing one-third dose with full dose and 1 year with 3 years of maintenance BCG. Eur Urol. 2014 Jan;65(1):69-76. doi: 10.1016/j.eururo.2013.07.021. Epub 2013 Jul 24.
citation: Oddens J, Brausi M, Sylvester R, Bono A, van de Beek C, van Andel G, Gontero P, Hoeltl W, Turkeri L, Marreaud S, Collette S, Oosterlinck W. Final results of an EORTC-GU cancers group randomized study of maintenance bacillus Calmette-Guerin in intermediate- and high-risk Ta, T1 papillary carcinoma of the urinary bladder: one-third dose versus full dose and 1 year versus 3 years of maintenance. Eur Urol. 2013 Mar;63(3):462-72. doi: 10.1016/j.eururo.2012.10.039. Epub 2012 Nov 2.