Clinical trial NCT00054626: Cisplatin and Gemcitabine Compared With Observation in Treating Patients Who Have Undergone Surgery for Bladder Cancer
Official title: Phase III Study Of Adjuvant Cisplatin-Gemcitabine Vs. Observation After Radical Cystectomy In High-Risk Bladder Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Bladder Cancer
Keywords: stage II bladder cancer
stage III bladder cancer
stage IV bladder cancer
transitional cell carcinoma of the bladder
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-02-06
Enrollment: 700
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. It is not yet known if combination chemotherapy is effective in preventing relapse in patients who have undergone radical cystectomy for bladder cancer.

PURPOSE: Phase III trial to compare the effectiveness of cisplatin combined with gemcitabine with that of observation in treating patients with bladder cancer who have undergone surgery to remove the bladder.

Detailed description: OBJECTIVES:

* Compare the overall, cause-specific, and disease-free survival of patients with high-risk muscle-invasive transitional cell carcinoma of the bladder treated with adjuvant cisplatin and gemcitabine vs observation after radical cystectomy.
* Compare the dose intensity and toxicity of two different schedules of cisplatin and gemcitabine in these patients.
* Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center and disease status (T2 \[G3 only\] or T3-4 \[any G\], N0-2 vs any T, N1-2, M0). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients are further randomized to 1 of 2 treatment regimens.

  * Regimen A: Patients receive cisplatin IV on day 2 and gemcitabine IV on days 1, 8, and 15.
  * Regimen B: Patients receive cisplatin IV on day 15 and gemcitabine as in regimen A.

Treatment in both regimens repeats every 28 days for 4 courses.

* Arm II: Patients undergo observation followed by cisplatin and gemcitabine as in arm I at relapse.

Patients are followed every 3 months for 2 years and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 700 patients (350 per treatment arm) will be accrued for this study within 3 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed transitional cell carcinoma of the bladder

  * T2 (G3 only) or T3-4 (any G), N0-2 or any T, N1-2, M0
  * No secondary localization
* Radical cystectomy (without residual disease) performed within 10 weeks prior to study entry to include:

  * Men: Cystectomy with removal of prostate and seminal vesicles including 1.5 cm of urethra plus pelvic lymphadenectomy (at least 15 negative lymph nodes are recommended to define as N0)
  * Women: Cystectomy with complete removal of the bladder, uterus, ovaries, and anterior walls of the vagina plus pelvic lymphadenectomy

PATIENT CHARACTERISTICS:

Age

* 18 to 74

Performance status

* ECOG 0-2

Life expectancy

* Not specified

Hematopoietic

* WBC at least 3,500/mm\^3
* Absolute neutrophil count at least 2,000/mm\^3
* Platelet count at least 100,000/mm\^3
* Hemoglobin at least 10 g/dL

Hepatic

* Bilirubin less than upper normal limit (ULN)
* Gamma-GT less than ULN
* SGOT and SGPT no greater than 2.5 times ULN
* Alkaline phosphatase no greater than 2.5 times ULN

Renal

* Creatinine no greater than1.25 times ULN
* Creatinine clearance at least 60 mL/min

Cardiovascular

* No congestive heart failure
* No angina pectoris
* No cardiac arrhythmia
* No uncontrolled arterial hypertension
* No history of acute myocardial infarction within the past year

Other

* No other serious concurrent illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* No prior systemic chemotherapy

Endocrine therapy

* Not specified

Radiotherapy

* Palliative radiotherapy allowed at relapse for symptomatic bone metastases

Surgery

* See Disease Characteristics

Primary outcomes:
measure: Overall survival at 5 years
Secondary outcomes:
measure: Disease-free survival at 5 years
measure: Local disease-free survival at 5 years
measure: Distant disease-free survival at 5 years
measure: Toxicity by WHO system grading after each course
measure: Quality of life after each course and every 6 months during follow-up
measure: Dose intensity at the end of the treatment
Other outcomes:
Locations:
city: Acireale - CT
country: Italy
facility: Ospedale Civile Via Caronia
city: Albano
country: Italy
facility: Ospedale S. Giuseppe
city: Alba
country: Italy
facility: Ospedale San Lazzaro
city: Alessandria
country: Italy
facility: Ospedale SS. Biagio e Arrigo
city: Alessandria
country: Italy
facility: Ospedale Civile Alessandria
city: Anagni
country: Italy
facility: Presidio Ospedale
city: Ancona - AN
country: Italy
facility: Istituto Nazionale Riposo e Cura Anziani Istituto
city: Ancona
country: Italy
facility: Ospedale Torrette University Ancona
city: Ancona
country: Italy
facility: Ospedale Generale Umberto 1
city: Arezzo
country: Italy
facility: Ospedale S. Donato
city: Asti
country: Italy
facility: Ospedale Civile di Asti
city: Avellino
country: Italy
facility: S.G. Moscati Hospital
city: Avezzano
country: Italy
facility: Ospedale Civile Avezzano
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico - Aviano
city: Bari-Carbonara
country: Italy
facility: Ospedale di Venere - Carbonara
city: Bari
country: Italy
facility: Universita Degli Studi di Bari
city: Bari
country: Italy
facility: Istituto Di Ricovero E Cura A Carattere Scientifico
city: Belluno
country: Italy
facility: Ospedale S. Martino
city: Bergamo
country: Italy
facility: Ospedali Riuniti di Bergamo
city: Biella
country: Italy
facility: Ospedale degli Infermi - ASL 12
city: Bologna
country: Italy
facility: Azienda Ospedaliera Di Bologna Policlinico S. Orsola - Malpighi
city: Bolzano
country: Italy
facility: Azienda Sanitaria di Bolzano
city: Borgomanero
country: Italy
facility: Ospedale S. Trinita
city: Brescia
country: Italy
facility: Spedali Civili di Brescia
city: Busto Arsizio
country: Italy
facility: Ospedale di Busto Arsizio
city: Cagliari
country: Italy
facility: Ospedale SS Trinita
city: Caltanissetta
country: Italy
facility: Ospedale Caltanissetta
city: Camposanpiero
country: Italy
facility: Ospedale Civile Camposanpiero
city: Candiolo
country: Italy
facility: Istituto per la Ricerca e Cura del Cancro
city: Carrara
country: Italy
facility: Civic Hospital of Carrara
city: Casale Monferrato
country: Italy
facility: Ospedale S. Spirito
city: Castellammare di Stabia - NA
country: Italy
facility: Ospedale S. Leonardo
city: Catania
country: Italy
facility: Ospedale Cannnizzaro
city: Catania
country: Italy
facility: Ospedale S. Luigi
city: Catanzaro
country: Italy
facility: Ospedale Regionale A. Pugliese
city: Chieti
country: Italy
facility: Ospedale SS Annunziata
city: Chieti
country: Italy
facility: Universita G.D'Annunzio Di Chieti
city: Cirie
country: Italy
facility: Ospedale Di Cirie
city: Como
country: Italy
facility: Ospedale Sant Anna
city: Crema
country: Italy
facility: Ospedale Maggiore Crema
city: Fano
country: Italy
facility: Ospedale Civile S. Croce
city: Fidenza
country: Italy
facility: Ospedale Fidenza
city: Florence
country: Italy
facility: Ospendale S.M. Annunziata-A.S.DI Florence
city: Forli
country: Italy
facility: Morgagni-Pierantoni Ospedale
city: Frascati - RM
country: Italy
facility: Ospedale S. Sebastiano
city: Frosinone
country: Italy
facility: Ospedale Umberto I
city: Gallarate Varese
country: Italy
facility: Ospedale S. Antonio Abate
city: Gela - CL
country: Italy
facility: Ospedale Di Gela
city: Genoa
country: Italy
facility: Istituto Nazionale per la Ricerca sul Cancro
city: Genoa
country: Italy
facility: Ospedale San Martino
city: Gorizia
country: Italy
facility: Presidio Ospedaliero-Gorizia
city: Grosseto
country: Italy
facility: Ospedale Misericordia USL 9
city: Grottaferrata
country: Italy
facility: INI Grottaferrata
city: Imola
country: Italy
facility: Ospedale Nuovo
city: Imola
country: Italy
facility: Ospedali Vecchi
city: Ivrea
country: Italy
facility: Ospedale Civile di Ivrea
city: La Spezia
country: Italy
facility: Ospendale S. Andrea EST
city: Lanciano
country: Italy
facility: Ospedale Civile Lanciano
city: Latina
country: Italy
facility: Ospedale Santa Maria Goretti
city: Lecco
country: Italy
facility: Ospedale Alessandro Manzoni
city: Legnano
country: Italy
facility: Ospedale Civile di Legnano
city: Livorno
country: Italy
facility: Presidio Ospedaliero di Livorno
city: Mantova
country: Italy
facility: Carlo Poma Hospital
city: Messina
country: Italy
facility: Ospedale Papardo
city: Messina
country: Italy
facility: Policlinico Messina
city: Milan
country: Italy
facility: University of Milan
city: Milan
country: Italy
facility: Ospedale San Giuseppe
city: Milan
country: Italy
facility: Istituto Scientifico H. San Raffaele
city: Milan
country: Italy
facility: European Institute of Oncology
city: Milan
country: Italy
facility: Ospedale Fatebene Fratelli
city: Milan
country: Italy
facility: Ospedale San Carlo Borromeo
city: Milan
country: Italy
facility: Ospedale Luigi Sacco
city: Modena
country: Italy
facility: Azienda Ospedaliera - Universitaria di Modena
city: Modena
country: Italy
facility: Sant Agostino - Estenes Institutes
city: Monserrato - CA
country: Italy
facility: Policlinico Monserrato
city: Monza
country: Italy
facility: Clinica Urologica II
city: Monza
country: Italy
facility: Ospedale San Gerardo
city: Naples
country: Italy
facility: Azienda Ospedaliera "A. Cardarelli"
city: Naples
country: Italy
facility: Federico II University Medical School
city: Naples
country: Italy
facility: Istituto Tumori/Fondazione Pascale
city: Negrar
country: Italy
facility: Ospedale Civile Negrar
city: Novara
country: Italy
facility: Azienda Ospedaliera Maggiore Della Carita
city: Orbassano
country: Italy
facility: Azienda Ospedale S. Luigi at University of Torino
city: Palermo
country: Italy
facility: Casa di Cura Noto Pasqualino
city: Palermo
country: Italy
facility: Ospedale Oncology M. Ascoli
city: Palermo
country: Italy
facility: Ospedale La Maddalena - Palermo
city: Parma
country: Italy
facility: Azienda Ospedaliera Di Parma
city: Pavia
country: Italy
facility: Fondazione I.R.C.C.S. Policlinico San Matteo
city: Pavia
country: Italy
facility: Universita Degli Studi
city: Pesaro
country: Italy
facility: Azienda Ospedale - d "S. Salvatore"
city: Pescara
country: Italy
facility: Ospedale Spiritito Santo
city: Pietra Ligure -SV
country: Italy
facility: Ospedale Santa Corona
city: Pisa
country: Italy
facility: Ospedale Santa Chiara Pisa
city: Pistoia
country: Italy
facility: Ospedale Pistoia
city: Pordenone
country: Italy
facility: Azienda Ospedaliera "Santa Maria Degli Angeli"
city: Potenza
country: Italy
facility: Azienda U.S.L. Cesena
city: Potenza
country: Italy
facility: Ospedale Carlo Forlanini
city: Rivoli
country: Italy
facility: Ospedale Di Rivoli
city: Rome
country: Italy
facility: Azienda Ospedaliera Sant'Andrea
city: Rome
country: Italy
facility: Ospedale C.T.O. Roma
city: Rome
country: Italy
facility: Ospedale Sant' Eugenio
city: Rome
country: Italy
facility: Azienda Ospedaliera S. Camillo-Forlanini
city: Rome
country: Italy
facility: Azienda Policlinico Umberto Primo
city: Rome
country: Italy
facility: Istituto Regina Elena
city: Rome
country: Italy
facility: Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore
city: Rome
country: Italy
facility: Fatebenefratelli, Isola Tiberina Hospital
city: Rome
country: Italy
facility: Ospedale San Pietro Fatebenefratelli
city: Rovigo
country: Italy
facility: Ospedale Civile di Rovigo
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: Saluzzo - CN
country: Italy
facility: Ospedale Saluzzo
city: San Daniele del Friuli
country: Italy
facility: Ospedale San Daniele del Friuli
city: San Giovanni - Rotondo
country: Italy
facility: Ospedale Casa Sollievo della Sofferenza
city: San Remo
country: Italy
facility: ASL NO. 1 Imperiese
city: San Remo
country: Italy
facility: Ospedale Civile G Borea
city: San Vito Al Talgliamento
country: Italy
facility: Ospedale Civile Di San Vito Al Tagliamento
city: Sandpierdarena
country: Italy
facility: Az. Ospedale Villa Scassi
city: Sassari
country: Italy
facility: Istituto Clinica Medica
city: Sassari
country: Italy
facility: Ospedale Civile ASL 1
city: Sassari
country: Italy
facility: Ospedale SS Trinita
city: Sassari
country: Italy
facility: Policlinico Sassari
city: Savigliano - CN
country: Italy
facility: Ospedali Savigliano
city: Savona
country: Italy
facility: Ospedale S. Paolo Valloria
city: Sestri Levante - GE
country: Italy
facility: Ospedale Civile Sestri Levante
city: Siena
country: Italy
facility: Universita di Siena
city: Siracusa
country: Italy
facility: Ospedale Umberto 1
city: Sondrio
country: Italy
facility: Osepdale Civile
city: Sora
country: Italy
facility: Ospedale SS Trinita
city: Sulmona
country: Italy
facility: SS Annunziata
city: Taormina
country: Italy
facility: Ospedale S. Vincenzo
city: Teramo
country: Italy
facility: Ospedale Civile Teramo
city: Thiene
country: Italy
facility: Ospedale Generale Prov. Boldrini
city: Tolmezzo Gemona F.
country: Italy
facility: Ospedale Civile
city: Trapani
country: Italy
facility: Ospedale Civile Trapani
city: Trento
country: Italy
facility: Ospedale Di Trento
city: Trento
country: Italy
facility: Primario U.O. di Oncologia Medica
city: Trieste
country: Italy
facility: Ospedale Cattinara
city: Turin
country: Italy
facility: Ospedale Amedeo Savoia
city: Turin
country: Italy
facility: Ospedale Martini
city: Turin
country: Italy
facility: Azienda Sanitaria Ospedale San Giovanni Battista Molinette di Torino
city: Turin
country: Italy
facility: Ospedale Gradenigo
city: Turin
country: Italy
facility: Ospedale Cottolengo
city: Turin
country: Italy
facility: Ospedale Giovanni Bosco
city: Turin
country: Italy
facility: Ospedale S. Giovanni Vecchio
city: Udine
country: Italy
facility: Azienda Ospedaliera Santa Maria della Misericordia
city: Venezia
country: Italy
facility: Ospedale Civile ULSS 12
city: Verbania
country: Italy
facility: Ospedale Civile Verbania
city: Vercelli
country: Italy
facility: Ospedal San Andrea
city: Verona
country: Italy
facility: Policlinico Borgo Roma
city: Verona
country: Italy
facility: Policlinico G. B. Rossi - Borgo Roma
city: Vicenza
country: Italy
facility: Ospedale San Bortolo
city: Viterbo
country: Italy
facility: Presidio Ospedaliero Belcolle
Study officials:
affiliation: Presidio Ospedaliero Belcolle
name: Camillo F. Pollera, MD
role: STUDY_CHAIR
References:
citation: Pollera CF, Merendino N, Cianciulli AM, et al.: Preliminary cytogenetic and pharmacogenomic analysis of muscle-invasive transitional-cell carcinoma (TCC) of the bladder in patients (pts) enrolled in the Italian National Research Council (CNR) phase III randomized trial comparing adjuvant cisplatin-gemcitabine (PG) vs observation (OBS) after radical cystectomy. [Abstract] J Clin Oncol 23 (Suppl 16): A-4589, 400s, 2005.