Cisplatin and Gemcitabine Compared With Observation in Treating Patients Who Have Undergone Surgery for Bladder Cancer

Bladder Cancer Clinical Trial

Official title:

Phase III Study Of Adjuvant Cisplatin-Gemcitabine Vs. Observation After Radical Cystectomy In High-Risk Bladder Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00054626
• Other study ID #: CDR0000258426
• Secondary ID: ITNRC-CU02.00447
• Status: Active, not recruiting
• Phase: Phase 3
• First received: February 5, 2003
• Last updated: December 17, 2013
• Start date: September 2001

Study information

• Verified date: November 2008
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 700
• Est. primary completion date: June 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 74 Years

Eligibility

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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Drug:
• cisplatin

• gemcitabine hydrochloride

Procedure:
• adjuvant therapy

Locations

Country	Name	City	State
Italy	Ospedale Civile Via Caronia	Acireale - CT
Italy	Ospedale San Lazzaro	Alba
Italy	Ospedale S. Giuseppe	Albano
Italy	Ospedale Civile Alessandria	Alessandria
Italy	Ospedale SS. Biagio e Arrigo	Alessandria
Italy	Presidio Ospedale	Anagni
Italy	Ospedale Generale Umberto 1	Ancona
Italy	Ospedale Torrette University Ancona	Ancona
Italy	Istituto Nazionale Riposo e Cura Anziani Istituto	Ancona - AN
Italy	Ospedale S. Donato	Arezzo
Italy	Ospedale Civile di Asti	Asti
Italy	S.G. Moscati Hospital	Avellino
Italy	Ospedale Civile Avezzano	Avezzano
Italy	Centro di Riferimento Oncologico - Aviano	Aviano
Italy	Istituto Di Ricovero E Cura A Carattere Scientifico	Bari
Italy	Universita Degli Studi di Bari	Bari
Italy	Ospedale di Venere - Carbonara	Bari-Carbonara
Italy	Ospedale S. Martino	Belluno
Italy	Ospedali Riuniti di Bergamo	Bergamo
Italy	Ospedale degli Infermi - ASL 12	Biella
Italy	Azienda Ospedaliera Di Bologna Policlinico S. Orsola - Malpighi	Bologna
Italy	Azienda Sanitaria di Bolzano	Bolzano
Italy	Ospedale S. Trinita	Borgomanero
Italy	Spedali Civili di Brescia	Brescia
Italy	Ospedale di Busto Arsizio	Busto Arsizio
Italy	Ospedale SS Trinita	Cagliari
Italy	Ospedale Caltanissetta	Caltanissetta
Italy	Ospedale Civile Camposanpiero	Camposanpiero
Italy	Istituto per la Ricerca e Cura del Cancro	Candiolo
Italy	Civic Hospital of Carrara	Carrara
Italy	Ospedale S. Spirito	Casale Monferrato
Italy	Ospedale S. Leonardo	Castellammare di Stabia - NA
Italy	Ospedale Cannnizzaro	Catania
Italy	Ospedale S. Luigi	Catania
Italy	Ospedale Regionale A. Pugliese	Catanzaro
Italy	Ospedale SS Annunziata	Chieti
Italy	Universita G.D'Annunzio Di Chieti	Chieti
Italy	Ospedale Di Cirie	Cirie
Italy	Ospedale Sant Anna	Como
Italy	Ospedale Maggiore Crema	Crema
Italy	Ospedale Civile S. Croce	Fano
Italy	Ospedale Fidenza	Fidenza
Italy	Ospendale S.M. Annunziata-A.S.DI Florence	Florence
Italy	Morgagni-Pierantoni Ospedale	Forli
Italy	Ospedale S. Sebastiano	Frascati - RM
Italy	Ospedale Umberto I	Frosinone
Italy	Ospedale S. Antonio Abate	Gallarate Varese
Italy	Ospedale Di Gela	Gela - CL
Italy	Istituto Nazionale per la Ricerca sul Cancro	Genoa
Italy	Ospedale San Martino	Genoa
Italy	Presidio Ospedaliero-Gorizia	Gorizia
Italy	Ospedale Misericordia USL 9	Grosseto
Italy	INI Grottaferrata	Grottaferrata
Italy	Ospedale Nuovo	Imola
Italy	Ospedali Vecchi	Imola
Italy	Ospedale Civile di Ivrea	Ivrea
Italy	Ospendale S. Andrea EST	La Spezia
Italy	Ospedale Civile Lanciano	Lanciano
Italy	Ospedale Santa Maria Goretti	Latina
Italy	Ospedale Alessandro Manzoni	Lecco
Italy	Ospedale Civile di Legnano	Legnano
Italy	Presidio Ospedaliero di Livorno	Livorno
Italy	Carlo Poma Hospital	Mantova
Italy	Ospedale Papardo	Messina
Italy	Policlinico Messina	Messina
Italy	European Institute of Oncology	Milan
Italy	Istituto Scientifico H. San Raffaele	Milan
Italy	Ospedale Fatebene Fratelli	Milan
Italy	Ospedale Luigi Sacco	Milan
Italy	Ospedale San Carlo Borromeo	Milan
Italy	Ospedale San Giuseppe	Milan
Italy	University of Milan	Milan
Italy	Azienda Ospedaliera - Universitaria di Modena	Modena
Italy	Sant Agostino - Estenes Institutes	Modena
Italy	Policlinico Monserrato	Monserrato - CA
Italy	Clinica Urologica II	Monza
Italy	Ospedale San Gerardo	Monza
Italy	Azienda Ospedaliera "A. Cardarelli"	Naples
Italy	Federico II University Medical School	Naples
Italy	Istituto Tumori/Fondazione Pascale	Naples
Italy	Ospedale Civile Negrar	Negrar
Italy	Azienda Ospedaliera Maggiore Della Carita	Novara
Italy	Azienda Ospedale S. Luigi at University of Torino	Orbassano
Italy	Casa di Cura Noto Pasqualino	Palermo
Italy	Ospedale La Maddalena - Palermo	Palermo
Italy	Ospedale Oncology M. Ascoli	Palermo
Italy	Azienda Ospedaliera Di Parma	Parma
Italy	Fondazione I.R.C.C.S. Policlinico San Matteo	Pavia
Italy	Universita Degli Studi	Pavia
Italy	Azienda Ospedale - d "S. Salvatore"	Pesaro
Italy	Ospedale Spiritito Santo	Pescara
Italy	Ospedale Santa Corona	Pietra Ligure -SV
Italy	Ospedale Santa Chiara Pisa	Pisa
Italy	Ospedale Pistoia	Pistoia
Italy	Azienda Ospedaliera "Santa Maria Degli Angeli"	Pordenone
Italy	Azienda U.S.L. Cesena	Potenza
Italy	Ospedale Carlo Forlanini	Potenza
Italy	Ospedale Di Rivoli	Rivoli
Italy	Azienda Ospedaliera S. Camillo-Forlanini	Rome
Italy	Azienda Ospedaliera Sant'Andrea	Rome
Italy	Azienda Policlinico Umberto Primo	Rome
Italy	Fatebenefratelli, Isola Tiberina Hospital	Rome
Italy	Istituto Regina Elena	Rome
Italy	Ospedale C.T.O. Roma	Rome
Italy	Ospedale San Pietro Fatebenefratelli	Rome
Italy	Ospedale Sant' Eugenio	Rome
Italy	Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore	Rome
Italy	Ospedale Civile di Rovigo	Rovigo
Italy	Istituto Clinico Humanitas	Rozzano
Italy	Ospedale Saluzzo	Saluzzo - CN
Italy	Ospedale San Daniele del Friuli	San Daniele del Friuli
Italy	Ospedale Casa Sollievo della Sofferenza	San Giovanni - Rotondo
Italy	ASL NO. 1 Imperiese	San Remo
Italy	Ospedale Civile G Borea	San Remo
Italy	Ospedale Civile Di San Vito Al Tagliamento	San Vito Al Talgliamento
Italy	Az. Ospedale Villa Scassi	Sandpierdarena
Italy	Istituto Clinica Medica	Sassari
Italy	Ospedale Civile ASL 1	Sassari
Italy	Ospedale SS Trinita	Sassari
Italy	Policlinico Sassari	Sassari
Italy	Ospedali Savigliano	Savigliano - CN
Italy	Ospedale S. Paolo Valloria	Savona
Italy	Ospedale Civile Sestri Levante	Sestri Levante - GE
Italy	Universita di Siena	Siena
Italy	Ospedale Umberto 1	Siracusa
Italy	Osepdale Civile	Sondrio
Italy	Ospedale SS Trinita	Sora
Italy	SS Annunziata	Sulmona
Italy	Ospedale S. Vincenzo	Taormina
Italy	Ospedale Civile Teramo	Teramo
Italy	Ospedale Generale Prov. Boldrini	Thiene
Italy	Ospedale Civile	Tolmezzo Gemona F.
Italy	Ospedale Civile Trapani	Trapani
Italy	Ospedale Di Trento	Trento
Italy	Primario U.O. di Oncologia Medica	Trento
Italy	Ospedale Cattinara	Trieste
Italy	Azienda Sanitaria Ospedale San Giovanni Battista Molinette di Torino	Turin
Italy	Ospedale Amedeo Savoia	Turin
Italy	Ospedale Cottolengo	Turin
Italy	Ospedale Giovanni Bosco	Turin
Italy	Ospedale Gradenigo	Turin
Italy	Ospedale Martini	Turin
Italy	Ospedale S. Giovanni Vecchio	Turin
Italy	Azienda Ospedaliera Santa Maria della Misericordia	Udine
Italy	Ospedale Civile ULSS 12	Venezia
Italy	Ospedale Civile Verbania	Verbania
Italy	Ospedal San Andrea	Vercelli
Italy	Policlinico Borgo Roma	Verona
Italy	Policlinico G. B. Rossi - Borgo Roma	Verona
Italy	Ospedale San Bortolo	Vicenza
Italy	Presidio Ospedaliero Belcolle	Viterbo

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione C.N.R./Regione Toscana "G. Monasterio", Pisa, Italy

Country where clinical trial is conducted

Italy, 

References & Publications (1)

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 ra

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival at 5 years			No
Secondary	Disease-free survival at 5 years			No
Secondary	Local disease-free survival at 5 years			No
Secondary	Distant disease-free survival at 5 years			No
Secondary	Toxicity by WHO system grading after each course			Yes
Secondary	Quality of life after each course and every 6 months during follow-up			No
Secondary	Dose intensity at the end of the treatment			No