Cisplatin Plus Gemcitabine With or Without Paclitaxel in Treating Patients With Stage IV Urinary Tract Cancer

Bladder Cancer Clinical Trial

Official title:

Randomized Phase III Study Comparing Paclitaxel/Cisplatin/Gemcitabine and Cisplatin/Gemcitabine in Patients With Metastatic or Locally Advanced Urothelial Cancer Without Prior Systemic Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00022191
• Other study ID #: EORTC-30987
• Secondary ID: EORTC-30987CAN-N
• Status: Completed
• Phase: Phase 3
• First received: August 10, 2001
• Last updated: June 11, 2013
• Start date: May 2001

Study information

• Verified date: June 2013
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• 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 tumor cells from dividing so they stop growing or die. It is not yet known which combination chemotherapy regimen is more effective for urinary tract cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of cisplatin plus gemcitabine with or without paclitaxel in treating patients who have stage IV urinary tract cancer.

Description:

OBJECTIVES:

• Compare the duration of survival of patients with stage IV transitional cell carcinoma of the urothelium treated with cisplatin and gemcitabine with or without paclitaxel.

• Compare the duration of progression-free survival, response rates, and duration of response in patients treated with these regimens.

• Compare the toxicity of these regimens in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to participating center, WHO performance status (0 vs 1), and presence of metastatic disease (yes vs no). Patients are randomized to one of two treatment arms.

• Arm I: Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 and cisplatin IV over 1 hour on day 1 or 2. Treatment repeats every 28 days for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients receive paclitaxel IV over 1 hour on days 1 and 8 followed by cisplatin IV over 1 hour on day 1 and gemcitabine IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity.

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

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 610 patients (305 per treatment arm) will be accrued for this study within 3.04 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 608
• Est. primary completion date: June 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed stage IV transitional cell carcinoma of the urothelium (pure or mixed) including bladder, urethra, ureter, and renal pelvis

• T4b, any N OR any T, N2-3 OR M1

• Ineligible for surgery or radiotherapy with curative intent

• Measurable or evaluable disease

• No known CNS metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• WHO 0-1

Life expectancy:

• At least 12 weeks

Hematopoietic:

• WBC at least 3,000/mm^3

• Platelet count at least 100,000/mm^3

• Hemoglobin at least 10 g/dL

Hepatic:

• Bilirubin less than 1.25 times normal

• AST or ALT less than 2.5 times normal

Renal:

• Glomerular filtration rate at least 60 mL/min

• Calcium normal or clinically insignificant

Cardiovascular:

• No clinically significant cardiac arrhythmia

• No congestive heart failure

• No complete bundle branch block

• No New York Heart Association class III or IV heart disease

Other:

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 6 months after study participation

• No psychological, familial, sociological, or geographical condition that would preclude study compliance

• No grade 3 or 4 infection without neutropenia

• No other serious concurrent systemic disorder that would preclude study therapy

• No mental disorder that would preclude study compliance

• No grade II or greater neuropathy

• No other prior or concurrent malignancy except appropriately treated carcinoma in situ of the cervix, basal cell carcinoma of the skin, or incidental prostate cancer (T1, Gleason score no greater than 6, and PSA less than 0.5 ng/mL)

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior investigational biologic agents (e.g., antiangiogenic products, signal transduction pathway inhibitors, immunomodulators, or monoclonal antibody therapy)

• At least 4 weeks since prior immunotherapy

Chemotherapy:

• No prior systemic chemotherapy

• At least 4 weeks since prior local intravesical chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics

• No more than 1 prior course of radiotherapy

• At least 4 weeks since prior radiotherapy and recovered

Surgery:

• See Disease Characteristics

• Prior urological procedures to relieve urinary tract obstruction and improve renal function allowed (e.g., ureteral stent or percutaneous nephrostomy)

Study Design

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bladder Cancer
• Carcinoma, Transitional Cell
• Kidney Neoplasms
• Transitional Cell Cancer of the Renal Pelvis and Ureter
• Ureteral Neoplasms
• Urethral Cancer
• Urinary Bladder Neoplasms

Intervention

Drug:
• cisplatin

• gemcitabine hydrochloride

• paclitaxel

Locations

Country	Name	City	State
Australia	Fremantle Hospital	Fremantle	Western Australia
Austria	Kaiser Franz Josef Hospital	Vienna
Belgium	Onze Lieve Vrouw Ziekenhuis Aalst	Aalst
Belgium	Academisch Ziekenhuis der Vrije Universiteit Brussel	Brussels
Belgium	Institut Jules Bordet	Brussels
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	CHU Liege - Domaine Universitaire du Sart Tilman	Liege
Canada	Royal Victoria Hospital, Barrie	Barrie	Ontario
Canada	William Osler Health Centre	Brampton	Ontario
Canada	Tom Baker Cancer Center - Calgary	Calgary	Alberta
Canada	Prince Edward Island Cancer Center at Queen Elizabeth Hospital	Charlottetown	Prince Edward Island
Canada	Complexe Hospitalier de la Sagamie	Chicoutimi	Quebec
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	CHUS-Hopital Fleurimont	Fleurimont	Quebec
Canada	Hopital Charles Lemoyne	Greenfield Park	Quebec
Canada	Nova Scotia Cancer Centre	Halifax	Nova Scotia
Canada	Hamilton and District Urology Association	Hamilton	Ontario
Canada	Margaret and Charles Juravinski Cancer Centre	Hamilton	Ontario
Canada	Centre Hospitalier Regional de Lanaudiere	Joliette	Quebec
Canada	British Columbia Cancer Agency - Centre for the Southern Interior	Kelowna	British Columbia
Canada	Kingston Regional Cancer Centre	Kingston	Ontario
Canada	Grand River Regional Cancer Centre	Kitchner	Ontario
Canada	Lethbridge Cancer Clinic	Lethbridge	Alberta
Canada	Hotel-Dieu de Levis	Levis	Quebec
Canada	Cancer Care Ontario-London Regional Cancer Centre	London	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	Markham Stouffville Hospital	Markham	Ontario
Canada	Credit Valley Hospital	Mississauga	Ontario
Canada	Trillium Health Centre	Mississauga	Ontario
Canada	Doctor Leon Richard Oncology Centre	Moncton	New Brunswick
Canada	Moncton Hospital	Moncton	New Brunswick
Canada	Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec
Canada	Hopital Du Sacre-Coeur de Montreal	Montreal	Quebec
Canada	Hopital Sainte Justine	Montreal	Quebec
Canada	Hotel Dieu de Montreal	Montreal	Quebec
Canada	Maisonneuve-Rosemont Hospital	Montreal	Quebec
Canada	McGill University	Montreal	Quebec
Canada	Nanaimo Cancer Clinic at Nanaimo Regional General Hospital	Nanaimo	British Columbia
Canada	Southlake Regional Health Centre	Newmarket	Ontario
Canada	Lions Gate Hospital	North Vancouver	British Columbia
Canada	North York General Hospital, Ontario	North York	Ontario
Canada	Sunnybrook and Women's College Health Sciences Centre	North York	Ontario
Canada	Male Health Centre - Oakville	Oakville	Ontario
Canada	Durham Regional Cancer Centre at Lakeridge Health Oshawa	Oshawa	Ontario
Canada	Ottawa Regional Cancer Centre	Ottawa	Ontario
Canada	Peterborough Oncology Clinic	Peterborough	Ontario
Canada	Centre Hospitalier Regional de Rimouski	Quebec
Canada	Centre Hospitalier Universitaire de Quebec	Quebec City	Quebec
Canada	Hopital du Saint-Sacrement, Quebec	Quebec City	Quebec
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Saint John Regional Hospital	Saint John	New Brunswick
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Algoma Reginal Cancer Program at Sault Area Hospital	Sault Sainte Marie	Ontario
Canada	Scarborough Hospital - General Site	Scarborough	Ontario
Canada	Hotel Dieu Health Sciences Hospital - Niagara	St. Catharines	Ontario
Canada	Newfoundland Cancer Treatment and Research Foundation	St. Johns	Newfoundland and Labrador
Canada	L'Hopital Laval	Ste-Foy	Quebec
Canada	Northeastern Ontario Regional Cancer Centre - Sudbury	Sudbury	Ontario
Canada	Cape Breton Cancer Centre	Sydney	Nova Scotia
Canada	Northwestern Ontario Regional Cancer Care	Thunder Bay	Ontario
Canada	Male Health Centre - North York	Toronto	Ontario
Canada	Mount Sinai Hospital - Toronto	Toronto	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	St. Joseph's Health Centre - Toronto	Toronto	Ontario
Canada	St. Michael's Hospital - Toronto	Toronto	Ontario
Canada	Toronto East General Hospital	Toronto	Ontario
Canada	Toronto General Hospital	Toronto	Ontario
Canada	Toronto Sunnybrook Regional Cancer Centre	Toronto	Ontario
Canada	British Columbia Cancer Agency	Vancouver	British Columbia
Canada	Prostate Centre at Vancouver General Hospital	Vancouver	British Columbia
Canada	Providence Health Care - Vancouver	Vancouver	British Columbia
Canada	British Columbia Cancer Agency - Vancouver Island Cancer Centre	Victoria	British Columbia
Canada	G. Steinhoff Clinical Research	Victoria	British Columbia
Canada	Humber River Regional Hospital - Weston	Weston	Ontario
Canada	Cancer Care Ontario - Windsor Regional Cancer Centre	Windsor	Ontario
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Denmark	Aarhus Kommunehospital	Aarhus
Denmark	Rigshospitalet	Copenhagen
France	Centre Paul Papin	Angers
France	Institut Bergonie	Bordeaux
France	Centre Hospitalier Docteur Duchenne	Boulogne Sur Mer
France	Centre Regional Francois Baclesse	Caen
France	Centre Hospitalier Universitaire Henri Mondor	Creteil
France	Centre de Lutte Contre le Cancer, Georges-Francois Leclerc	Dijon
France	CHU de Grenoble - Hopital de la Tronche	Grenoble
France	Centre Hospitalier Departemental	La Roche Sur Yon
France	Centre Oscar Lambret	Lille
France	Centre Leon Berard	Lyon
France	CHU de la Timone	Marseille
France	Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle	Montpellier
France	Hopital Lapeyronie-CHU Montpellier	Montpellier
France	Centre Regional Rene Gauducheau	Nantes-Saint Herblain
France	Hopital Europeen Georges Pompidou	Paris
France	Hopital Tenon	Paris
France	Institut Curie - Section Medicale	Paris
France	Centre Eugene Marquis	Rennes
France	Centre Henri Becquerel	Rouen
France	Centre Rene Huguenin	Saint Cloud
France	Centre Medico-Chirurgical Foch	Suresnes
France	Centre Antoine Lacassagne	Toulouse
France	Institut Claudius Regaud	Toulouse
France	Centre Alexis Vautrin	Vandoeuvre-les-Nancy
Germany	Krankenhaus Hohe Warte Mediziniche Klinik	Bayreuth
Germany	Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin	Berlin
Germany	Charite Humboldt - University Berlin	Berlin
Germany	Helios - Klinik Blankenhain	Blankenhain
Germany	Universitaetsklinikum Bonn	Bonn
Germany	Staedtische Kliniken Dortmund	Dortmund
Germany	Universitaetsklinik Duesseldorf	Duesseldorf
Germany	Klinikum der J.W. Goethe Universitaet	Frankfurt
Germany	St. Markus Krankenhaus	Frankfurt
Germany	Klinikum Fulda	Fulda
Germany	Martin Luther Universitaet	Halle
Germany	Marienkrankenhaus	Hamburg
Germany	Universitat des Saarlandes Innere Medizin 1	Hamburg
Germany	Klinikum der Friedrich-Schiller Universitaet Jena	Jena
Germany	Klinikum der Stadt Ludwigshafen am Rhein	Ludwigshafen am Rhein
Germany	Medizinische Universitaet Luebeck	Luebeck
Germany	Staedtisches Krankenhaus Sued	Luebeck
Germany	Kreiskrankenhaus Luedenscheid	Luedenscheid
Germany	Klinikum der Stadt Mannheim	Mannheim
Germany	University of Marburg	Marburg
Germany	Klinik und Poliklinik fuer Kinderheilkunde	Muenster
Germany	Klinikum Rechts Der Isar - Technische Universitaet Muenchen	Munich
Germany	Klinikum Neubrandenburg	Neubrandenburg
Germany	Klinikum Nuernberg - Klinikum Nord	Nuernberg
Germany	Paracelsus Karankenhaus Ruit	Ostfildern
Germany	Asklepios Klinik Pasewalk	Pasewalk
Germany	Diakonie - Krankenhaus	Rotenburg
Germany	Johanniter Kankenhaus Stendal	Stendal
Germany	Katharinenhospital	Stuttgart
Germany	Universitaetsklinikum Tuebingen	Tuebingen
Germany	Universitaet Ulm	Ulm
Germany	Klinikum der Stadt Wolfsburg	Wolfsburg
Germany	Klinikum St. Marien	Wuppertal
Germany	Witten University - Klinikum Wuppertal	Wuppertal
Hungary	National Institute of Oncology	Budapest
Israel	Rabin Medical Center - Beilinson Campus	Petah-Tikva
Israel	Assaf Harofeh Medical Center	Zerifin
Italy	Ospedale Santa Croce	Cuneo
Italy	Istituto Scientifico H.San Raffaele	Milano
Netherlands	Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital	Amsterdam
Netherlands	Jeroen Bosch Ziekenhuis	NL'S Hertogenbosch
Netherlands	Daniel Den Hoed Cancer Center at Erasmus Medical Center	Rotterdam
Netherlands	Academisch Ziekenhuis Utrecht	Utrecht
Netherlands	University Hospital - Rotterdam Dijkzigt	Utrecht
Poland	Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology	Warsaw
Slovakia	National Cancer Institute - Bratislava	Bratislava
Spain	Hospital Universitari Germans Trias i Pujol	Badalona
Spain	Hospital Clinic y Provincial de Barcelona	Barcelona
Spain	Hospital Del Mar	Barcelona
Spain	Hospital General Universitari Vall d'Hebron	Barcelona
Spain	Hospital Juan Canalejo	Coruna
Spain	Hospital General Universitario De Guadalajara	Guadalajara
Spain	Hospital Cuidad de Jaen	Jaen
Spain	Hospital Arquitecto Marcide	La Coruna
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario San Carlos	Madrid
Spain	Hospital Clinico Universitario - Malaga	Malaga
Spain	Hospital Son Dureta	Palma De Mallorca
Spain	Hospsital de Sabadell	Sabadell
Spain	Hospital Universitario Marques de Valdecilla	Santander
Spain	Hospital Consorci Sanitari De Terrassa	Terrassa
Spain	Hospital Clinico Universitario de Valencia	Valencia
Spain	Instituto Valenciano De Oncologia	Valencia
Spain	Hospital Rio Hortega	Valladolid
Spain	Hospital General De Vic	Vic
Spain	Hospital Clinico Universitario	Zaragoza
United Kingdom	Velindre Cancer Center at Velinde Hospital	Cardiff	Wales
United Kingdom	Princess Royal Hospital	Hull	England
United Kingdom	St. James's University Hospital	Leeds	England
United Kingdom	Guy's and St. Thomas' Hospitals NHS Trust	London	England
United Kingdom	Saint Bartholomew's Hospital	London	England
United Kingdom	Northern Centre for Cancer Treatment at Newcastle General Hospital	Newcastle Upon Tyne	England
United Kingdom	Royal South Hants Hospital	Southampton	England
United Kingdom	Royal Marsden Hospital - Sutton	Sutton	England
United States	Harrington Cancer Center	Amarillo	Texas
United States	Veterans Affairs Medical Center - Amarillo	Amarillo	Texas
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Veterans Affairs Medical Center - Ann Arbor	Ann Arbor	Michigan
United States	University of Colorado Cancer Center at University of Colorado Health Sciences Center	Aurora	Colorado
United States	Veterans Affairs Medical Center - Biloxi	Biloxi	Mississippi
United States	Cancer Research Center at Boston Medical Center	Boston	Massachusetts
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	Veterans Affairs Medical Center - Charleston	Charleston	South Carolina
United States	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio
United States	Veterans Affairs Medical Center - Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Del Rio	Texas
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	St. Mary's - Duluth Clinic Cancer Center	Duluth	Minnesota
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	University of Texas Medical Branch	Galveston	Texas
United States	Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital)	Hines	Illinois
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Veterans Affairs Medical Center - Jackson	Jackson	Mississippi
United States	CCOP - Kansas City	Kansas City	Missouri
United States	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas
United States	Veterans Affairs Medical Center - Kansas City	Kansas City	Missouri
United States	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky
United States	Veterans Affairs Medical Center - Lexington	Lexington	Kentucky
United States	Veterans Affairs Medical Center - Little Rock (McClellan)	Little Rock	Arkansas
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	Southwest Cancer and Research Center at University Medical Center	Lubbock	Texas
United States	Veterans Affairs Outpatient Clinic - Martinez	Martinez	California
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	University of Tennessee Cancer Institute	Memphis	Tennessee
United States	Veterans Affairs Medical Center - Memphis	Memphis	Tennessee
United States	Tulane University School of Medicine	New Orleans	Louisiana
United States	Veterans Affairs Medical Center - New Orleans	New Orleans	Louisiana
United States	Herbert Irving Comprehensive Cancer Center at Columbia University	New York	New York
United States	Oklahoma University Medical Center at University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Veterans Affairs Medical Center - Oklahoma City	Oklahoma City	Oklahoma
United States	Chao Family Comprehensive Cancer Center at University of California Irvine Cancer Center	Orange	California
United States	Cancer Institute at Oregon Health and Science University	Portland	Oregon
United States	Veterans Affairs Medical Center - Portland	Portland	Oregon
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	University of California Davis Cancer Center	Sacramento	California
United States	St. Louis University Hospital Cancer Center	Saint Louis	Missouri
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	Veterans Affairs Medical Center - Salt Lake City	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Veterans Affairs Medical Center - San Antonio (Murphy)	San Antonio	Texas
United States	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington
United States	Veterans Affairs Medical Center - Seattle	Seattle	Washington
United States	Louisiana State University Health Sciences Center - Shreveport	Shreveport	Louisiana
United States	Veterans Affairs Medical Center - Shreveport	Shreveport	Louisiana
United States	Providence Cancer Institute at Providence Hospital	Southfield	Michigan
United States	Arizona Cancer Center at University of Arizona Health Sciences Center	Tucson	Arizona
United States	Veterans Affairs Medical Center - Tucson	Tucson	Arizona

Sponsors (10)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC	Canadian Cancer Trials Group, Central European Cooperative Oncology Group, German Association of Urologic Oncology, Groupe D'Etude des Tumeurs Uro-Genitales, Institute of Cancer Research, United Kingdom, Medical Research Council, National Cancer Institute (NCI), Southwest Oncology Group, Spanish Oncology Genito-Urinary Group

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Denmark,  France,  Germany,  Hungary,  Israel,  Italy,  Netherlands,  Poland,  Slovakia,  Spain,  United Kingdom, 

References & Publications (1)

Bellmunt J, von der Maase H, Mead GM, Skoneczna I, De Santis M, Daugaard G, Boehle A, Chevreau C, Paz-Ares L, Laufman LR, Winquist E, Raghavan D, Marreaud S, Collette S, Sylvester R, de Wit R. Randomized phase III study comparing paclitaxel/cisplatin/gemc — View Citation