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.

Condition	Treatment or Intervention	Phase
stage II bladder cancer stage III bladder cancer stage IV bladder cancer transitional cell carcinoma of the bladder	Drug: cisplatin  Drug: gemcitabine  Procedure: adjuvant therapy  Procedure: chemotherapy	Phase III

Further Study Details: 

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.

• 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.
• 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.

Ages Eligible for Study:  18 Years   -   74 Years,  Genders Eligible for Study:  Both

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

Italy
      ASL NO. 1 Imperiese, San Remo,  18038,  Italy; Recruiting
      Az. Ospedale Villa Scassi, Sandpierdarena,  16100,  Italy; Recruiting
      Azienda Ospedale S. Luigi - Universita Di Turin, Orbassano,  10043,  Italy; Recruiting
      Azienda Ospedaliera "A. Cardarelli", Naples,  80127,  Italy; Recruiting
      Azienda Ospedaliera "Santa Maria Degli Angeli", Pordenone,  33170,  Italy; Recruiting
      Azienda Ospedaliera Di Bologna Policlinico S. Orsola - Malpighi, Bologna,  40138,  Italy; Recruiting
      Azienda Ospedaliera Di Parma, Parma,  43100,  Italy; Recruiting
      Azienda Ospedaliera Maggiore Della Carita, Novara,  28100,  Italy; Recruiting
      Azienda Ospedaliera Santa Maria della Misericordia, Udine,  33100,  Italy; Recruiting
      Azienda Policlinico Umberto Primo, Rome,  00161,  Italy; Recruiting
      Azienda Sanitaria di Bolzano, Bolzano,  39100,  Italy; Recruiting
      Azienda Sanitaria Ospedale San Giovanni Battista Molinette di Torino, Turin,  10126,  Italy; Recruiting
      Azienda U.S.L. Cesena, Potenza,  85100,  Italy; Recruiting
      C.T.O. Roma, Roma,  00100,  Italy; Recruiting
      Carlo Poma Hospital, Mantova,  46100,  Italy; Recruiting
      Casa di Cura Noto Pasqualino, Palermo,  90100,  Italy; Recruiting
      Centro di Riferimento Oncologico - Aviano, Aviano,  33081,  Italy; Recruiting
      Civic Hospital of Carrara, Carrara,  I-54033,  Italy; Recruiting
      Clinica Urologica II, Monza,  20052,  Italy; Recruiting
      European Institute of Oncology, Milano,  20141,  Italy; Recruiting
      Fatebenefratelli, Isola Tiberina Hospital, Rome,  00186,  Italy; Recruiting
      Federico II University Medical School, Naples,  80131,  Italy; Recruiting
      I.R.C.C.S. Policlinico San Matteo, Pavia,  27100,  Italy; Recruiting
      INI Grottaferrata, Grottaferrata,  00046,  Italy; Recruiting
      Istituto Clinica Medica, Sassari,  07100,  Italy; Recruiting
      Istituto Clinico Humanitas, Rozzano,  20089,  Italy; Recruiting
      Istituto Di Ricovero E Cura A Carattere Scientifico, Bari,  70126,  Italy; Recruiting
      Istituto Nazionale per la Ricerca sul Cancro, Genoa,  16132,  Italy; Recruiting
      Istituto Nazionale Riposo e Cura Anziani Istituto, Ancona - AN,  60100,  Italy; Recruiting
      Istituto per la Ricerca e Cura del Cancro, Candiolo,  10060,  Italy; Recruiting
      Istituto Regina Elena, Rome,  00161,  Italy; Recruiting
      Istituto Scientifico H. San Raffaele, Milano,  20132,  Italy; Recruiting
      Istituto Tumori/Fondazione Pascale, Naples,  80131,  Italy; Recruiting
      Morgagni-Pierantoni Ospedale, Forli,  47100,  Italy; Recruiting
      Osepdale Civile, Sondrio,  23100,  Italy; Recruiting
      Ospedal San Andrea, Vercelli,  13100,  Italy; Recruiting
      Ospedale S. Donato, Arezzo,  52100,  Italy; Recruiting
      Ospedale A. Manzoni, Lecco,  23900,  Italy; Recruiting
      Ospedale Amedeo Savoia, Turin,  10100,  Italy; Recruiting
      Ospedale Caltanissetta, Caltanissetta,  93100,  Italy; Recruiting
      Ospedale Cannnizzaro, Catania,  95100,  Italy; Recruiting
      Ospedale Carlo Forlanini, Potenza,  85100,  Italy; Recruiting
      Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo,  71013,  Italy; Recruiting
      Ospedale Cattinara, Trieste,  Italy; Recruiting
      Ospedale Civile, Bassano del Grappa,  36061,  Italy; Recruiting
      Ospedale Civile Alessandria, Alessandria,  I-15100,  Italy; Recruiting
      Ospedale Civile ASL 1, Sassari,  07100,  Italy; Recruiting
      Ospedale Civile Avezzano, Avezzano,  67051,  Italy; Recruiting
      Ospedale Civile Camposanpiero, Camposanpiero,  35012,  Italy; Recruiting
      Ospedale Civile di Asti, Asti,  14100,  Italy; Recruiting
      Ospedale Civile di Ivrea, Ivrea,  10015,  Italy; Recruiting
      Ospedale Civile di Rovigo, Rovigo,  45100,  Italy; Recruiting
      Ospedale Civile Di San Vito Al Tagliamento, San Vito Al Talgliamento,  Italy; Recruiting
      Ospedale Civile G Borea, San Remo,  18038,  Italy; Recruiting
      Ospedale Civile Lanciano, Lanciano,  66034,  Italy; Recruiting
      Ospedale Civile Maggiore - Borgo Trento, Verona,  37126,  Italy; Recruiting
      Ospedale Civile Negrar, Negrar,  37024,  Italy; Recruiting
      Ospedale Civile S. Croce, Fano,  61032,  Italy; Recruiting
      Ospedale Civile Sestri Levante, Sestri Levante - GE,  16039,  Italy; Recruiting
      Ospedale Civile Teramo, Teramo,  64100,  Italy; Recruiting
      Ospedale Civile Trapani, Trapani,  91100,  Italy; Recruiting
      Ospedale Civile ULSS 12, Venezia,  30100,  Italy; Recruiting
      Ospedale Civile Verbania, Verbania,  28900,  Italy; Recruiting
      Ospedale Civile Via Caronia, Acireale - CT,  95024,  Italy; Recruiting
      Ospedale Civile, Chivasso - TO,  10034,  Italy; Recruiting
      Ospedale Civile, Novi Ligure - AL,  15067,  Italy; Recruiting
      Ospedale Civile, Castelfranco - TV,  31033,  Italy; Recruiting
      Ospedale Civile, Tolmezzo Gemona F.,  33013,  Italy; Recruiting
      Ospedale Civile, Villafranca - VR,  37069,  Italy; Recruiting
      Ospedale Civile, Genoa,  16100,  Italy; Recruiting
      Ospedale Cottolengo, Turin,  Italy; Recruiting
      Ospedale degli Infermi - ASL 12, Biella,  13900,  Italy; Recruiting
      Ospedale di Busto Arsizio, Busto Arsizio,  21052,  Italy; Recruiting
      Ospedale Di Cirie, Cirie,  10073,  Italy; Recruiting
      Ospedale Di Gela, Gela - CL,  930123,  Italy; Recruiting
      Ospedale di Legnano, Legnano,  20025,  Italy; Recruiting
      Ospedale Di Rivoli, Rivoli,  10098,  Italy; Recruiting
      Ospedale Di Trento, Trento,  38100,  Italy; Recruiting
      Ospedale di Venere - Carbonara, Bari-Carbonara,  70100,  Italy; Recruiting
      Ospedale Fatebene Fratelli, Milan,  20152,  Italy; Recruiting
      Ospedale Fidenza, Fidenza,  43036,  Italy; Recruiting
      Ospedale Fratebenefratelli, Roma,  00100,  Italy; Recruiting
      Ospedale Gen. Provinciale Santa Maria Goretti, Latina,  04100,  Italy; Recruiting
      Ospedale Generale Prov. Boldrini, Thiene,  36016,  Italy; Recruiting
      Ospedale Generale Umberto 1, Ancona,  60100,  Italy; Recruiting
      Ospedale Giovanni Bosco, Turin,  Italy; Recruiting
      Ospedale Gradenigo, Turin,  10153,  Italy; Recruiting
      Ospedale La Maddalena - Palermo, Palermo,  Italy; Recruiting
      Ospedale L'Aquila, L'Aquila,  67100,  Italy; Recruiting
      Ospedale Luigi Sacco, Milan,  20157,  Italy; Recruiting
      Ospedale Maggiore Crema, Crema,  26013,  Italy; Recruiting
      Ospedale Martini, Turin,  10100,  Italy; Recruiting
      Ospedale Misericordia USL 9, Grosseto,  58100,  Italy; Recruiting
      Ospedale Nuovo, Imola,  40026,  Italy; Recruiting
      Ospedale Oncology M. Ascoli, Palermo,  90100,  Italy; Recruiting
      Ospedale Papardo, Messina,  98100,  Italy; Recruiting
      Ospedale Pistoia, Pistoia,  51100,  Italy; Recruiting
      Ospedale Regionale A. Pugliese, Catanzaro,  88100,  Italy; Recruiting
      Ospedale Regionale, Aosta,  11100,  Italy; Recruiting
      Ospedale S. Leonardo, Castellammare di Stabia - NA,  80053,  Italy; Recruiting
      Ospedale S. Andrea, Roma,  00100,  Italy; Recruiting
      Ospedale S. Antonio Abate, Gallarate Varese,  21013,  Italy; Recruiting
      Ospedale S. Camillo, Roma,  00100,  Italy; Recruiting
      Ospedale S. Giovanni Vecchio, Turin,  Italy; Recruiting
      Ospedale S. Giuseppe, Albano,  00041,  Italy; Recruiting
      Ospedale S. Luigi, Catania,  95100,  Italy; Recruiting
      Ospedale S. Martino, Belluno,  32100,  Italy; Recruiting
      Ospedale S. Paolo Valloria, Savona,  17100,  Italy; Recruiting
      Ospedale S. Sebastiano, Frascati - RM,  00044,  Italy; Recruiting
      Ospedale S. Spirito, Casale Monferrato,  15033,  Italy; Recruiting
      Ospedale S. Trinita, Borgomanero,  28021,  Italy; Recruiting
      Ospedale S. Vincenzo, Taormina,  98039,  Italy; Recruiting
      Ospedale Saluzzo, Saluzzo - CN,  12037,  Italy; Recruiting
      Ospedale San Bortolo, Vicenza,  36100,  Italy; Recruiting
      Ospedale San Carlo Borromeo, Milan,  20153,  Italy; Recruiting
      Ospedale San Daniele del Friuli, San Daniele del Friuli,  33038,  Italy; Recruiting
      Ospedale San Gerardo, Monza,  20052,  Italy; Recruiting
      Ospedale San Giuseppe, Milano,  20100,  Italy; Recruiting
      Ospedale San Lazzaro, Alba,  12051,  Italy; Recruiting
      Ospedale San Martino/Cliniche Universitarie Convenzionate, Genoa,  16132,  Italy; Recruiting
      Ospedale San Salvatore, Pesaro,  I-61100,  Italy; Recruiting
      Ospedale Sant Anna, Como,  22100,  Italy; Recruiting
      Ospedale Sant' Eugenio, Rome,  00144,  Italy; Recruiting
      Ospedale Santa Chiara, Pisa,  I-56126,  Italy; Recruiting
      Ospedale Santa Corona, Pietra Ligure -SV,  17029,  Italy; Recruiting
      Ospedale Spiritito Santo, Pescara,  65100,  Italy; Recruiting
      Ospedale SS Annunziata, Chieti,  66100,  Italy; Recruiting
      Ospedale SS Trinita, Sassari,  07100,  Italy; Recruiting
      Ospedale SS Trinita, Cagliari,  09100,  Italy; Recruiting
      Ospedale SS Trinita, Sora,  03039,  Italy; Recruiting
      Ospedale SS. Biagio e Arrigo, Alessandria,  15100,  Italy; Recruiting
      Ospedale Torrette University Ancona, Ancona,  60020,  Italy; Recruiting
      Ospedale Umberto 1, Siracusa,  95100,  Italy; Recruiting
      Ospedale Umberto I, Frosinone,  03100,  Italy; Recruiting
      Ospedali Riuniti di Bergamo, Bergamo,  24100,  Italy; Recruiting
      Ospedali Riuniti, Reggio Calabria,  89100,  Italy; Recruiting
      Ospedali Savigliano, Savigliano - CN,  12038,  Italy; Recruiting
      Ospedali Vecchi, Imola,  40026,  Italy; Recruiting
      Ospendale S. Andrea EST, La Spezia,  19100,  Italy; Recruiting
      Ospendale S.M. Annunziata-A.S.DI Florence, Florence,  I-50011,  Italy; Recruiting
      Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore, Rome,  00168,  Italy; Recruiting
      Policlinico Borgo Roma, Verona,  37134,  Italy; Recruiting
      Policlinico di Modena, Modena,  41100,  Italy; Recruiting
      Policlinico Messina, Messina,  98123,  Italy; Recruiting
      Policlinico Monserrato, Monserrato - CA,  09042,  Italy; Recruiting
      Policlinico Monteluce, Perugia,  06100,  Italy; Recruiting
      Policlinico P. Giaccone - Universita Di Palermo, Palermo,  90127,  Italy; Recruiting
      Policlinico Sassari, Sassari,  07100,  Italy; Recruiting
      Presidio Ospedale, Anagni,  03012,  Italy; Recruiting
      Presidio Ospedaliero Belcolle, Viterbo,  I-01100,  Italy; Recruiting
      Presidio Ospedaliero, Livorno,  57100,  Italy; Recruiting
      Presidio Ospedaliero-Gorizia, Gorizia,  34170,  Italy; Recruiting
      Primario U.O. di Oncologia Medica, Trento,  38100,  Italy; Recruiting
      S.G. Moscati Hospital, Avellino,  83100,  Italy; Recruiting
      Sant Agostino - Estenes Institutes, Modena,  41100,  Italy; Recruiting
      Spedali Civili di Brescia, Brescia,  25124,  Italy; Recruiting
      SS Annunziata, Sulmona,  67039,  Italy; Recruiting
      Universita Degli Studi di Bari Policlinico, Bari,  70124,  Italy; Recruiting
      Universita Degli Studi, Pavia,  27100,  Italy; Recruiting
      Universita di Siena, Siena,  53100,  Italy; Recruiting
      Universita G.D'Annunzio Di Chieti, Chieti,  66100,  Italy; Recruiting
      University of Genoa, Genoa,  Italy; Recruiting
      University of Milan, Milan,  20122,  Italy; Recruiting

Study chairs or principal investigators

Camillo F. Pollera, MD,  Study Chair,  Presidio Ospedaliero Belcolle   

Study ID Numbers:  CDR0000258426; ITNRC-CU02.00447ST/97; NCI-V02-1715; NCT00054626
Record last reviewed:  January 2004
Last Updated:  March 21, 2005
Record first received:  February 5, 2003
ClinicalTrials.gov Identifier:  NCT00054626
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08