MedPath

Letrozole in Preventing Cancer in Postmenopausal Women Who Have Received 4-6 Years of Hormone Therapy for Hormone Receptor-Positive, Lymph Node-Positive, Early-Stage Breast Cancer

Phase 3
Completed
Conditions
Breast Cancer
Interventions
Registration Number
NCT00553410
Lead Sponsor
ETOP IBCSG Partners Foundation
Brief Summary

RATIONALE: Estrogen can cause the growth of breast cancer cells. Letrozole may fight breast cancer by lowering the amount of estrogen the body makes. It is not yet known which regimen of letrozole is more effective in postmenopausal women who have received hormone therapy for early-stage breast cancer.

PURPOSE: This randomized phase III trial is comparing two different regimens of letrozole in preventing cancer in postmenopausal women who have received 4-6 years of hormone therapy for hormone receptor-positive, lymph node-positive, early-stage breast cancer.

Detailed Description

OBJECTIVES:

Primary

* Compare the disease-free survival (DFS) of postmenopausal women treated with continuous letrozole for 5 years vs intermittent letrozole over a 5-year period.

Secondary

* Compare overall survival of patients treated with these two regimens.

* Compare distant DFS of these patients.

* Compare breast cancer-free interval of these patients.

* Compare sites of first DFS failure in these patients.

* Compare second (nonbreast) malignancies in these patients.

* Compare deaths without prior cancer events in these patients.

* Compare adverse events resulting from these two regimens.

OUTLINE: This is a multicenter study. Patients are stratified according to treatment center and type of prior endocrine therapy (selective estrogen receptor modulators \[SERMs\] alone vs aromatase inhibitors \[AIs\] alone vs both SERMs and AIs each for at least 1 month). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive oral letrozole daily for 5 years.

* Arm II: Patients receive oral letrozole daily for the first 9 months of years 1 through 4, followed by 12 months in year 5.

After completion of study therapy, patients are followed annually.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
4884
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Continuous letrozoleLetrozoleContinuous letrozole: 5 years continuously (2.5 mg Letrozole daily)
Intermittent letrozoleLetrozoleIntermittent letrozole: 48 months over 5 yrs: 4 x 9 months (9 mo followed by 3 mo treatment-free interval in yrs 1-4, -\> 36 mo) plus 1 x 12 mo in yr 5 -\> 48 months
Primary Outcome Measures
NameTimeMethod
Disease-free Survival (DFS)5-year estimates, reported at a median follow-up of 60 months

Duration of time from randomization to the first indication of the following events: invasive recurrence at local (including recurrence restricted to the breast after breast conserving treatment), regional or distant sites; a new invasive cancer in the contralateral breast; any second (non-breast) invasive malignancy; or a death without prior cancer event. Appearance of DCIS or LCIS either in the ipsilateral or in the contralateral breast was not be considered as an event for DFS. In the absence of an event, DFS was censored at the date of last follow-up visit.

Secondary Outcome Measures
NameTimeMethod
Overall Survival5-year estimates, reported at a median follow-up of 60 months

Duration of time from randomization to death from any cause, or was censored at the date last known alive. (Note, for patients who withdrew consent or were lost to follow-up but follow-up for survival was possible through hospital or registry records, OS was censored at the date last known alive rather than date of last follow-up/withdrawn consent).

Breast Cancer-free Interval5-year estimates, reported at a median follow-up of 60 months

Duration of time from randomization to the first indication of the following events: invasive breast recurrence at local, regional or distant sites; a new invasive cancer in the contralateral breast (second non-breast malignancies are ignored). In the absence of an event, BCFI was censored at the date of last follow-up visit or date of death without prior breast cancer event.

Distant Recurrence-free Interval (DRFI)5-year estimates, reported at a median follow-up of 60 months

Duration of time from randomization to the first indication of invasive breast recurrence at a distant site. In the absence of an event, DRFI was censored at the date of last follow-up visit or date or death without distant recurrence.\*

\*This endpoint replaced DDFS, which was specified in the protocol

Trial Locations

Locations (163)

Centre Hospitalier Universitaire Vaudois

🇨🇭

Lausanne, Switzerland

Innsbruck Universitaetsklinik

🇦🇹

Innsbruck, Austria

Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

Hanusch-Krankenhaus

🇦🇹

Vienna, Austria

Armidale Hospital

🇦🇺

Armidale, New South Wales, Australia

Faulkner Hospital

🇺🇸

Boston, Massachusetts, United States

Concord Repatriation General Hospital

🇦🇺

Concord, New South Wales, Australia

A. Perrino Hospital

🇮🇹

Brindisi, Italy

Christchurch Hospital

🇳🇿

Christchurch, New Zealand

Tokyo Metropolitan - Komagome Hospital

🇯🇵

Tokyo, Japan

Tygerberg Hospital

🇿🇦

Kapstadt, South Africa

Azienda Istituti Ospitalieri

🇮🇹

Cremona, Italy

Instituto Nacional de Enfermedades Neoplasicas

🇵🇪

Lima, Peru

Centro di Riferimento Oncologico - Aviano

🇮🇹

Aviano, Italy

Spedali Civili di Brescia

🇮🇹

Brescia, Italy

Vall d'Hebron University Hospital

🇪🇸

Barcelona, Spain

Hospital Son Llatzer

🇪🇸

Palma De Mallorca, Spain

Kumamoto University Faculty of Medical and Pharmaceutical Sciences

🇯🇵

Kumamoto, Japan

Sagara Hospital

🇯🇵

Kagoshima, Japan

Ospedale "la Carita", Locarno

🇨🇭

Locarno, Switzerland

Tumor Zentrum ZeTup St. Gallen und Chur

🇨🇭

St. Gallen, Switzerland

Lasarettet i Boras

🇸🇪

Boras, Sweden

Yao Municipal Hospital

🇯🇵

Osaka, Japan

Niigata Cancer Center Hospital

🇯🇵

Niigata, Japan

Ospedale degli Infermi - ASL 12

🇮🇹

Biella, Italy

Ospedale Civile Rimini

🇮🇹

Rimini, Italy

Hospital Ramon y Cajal

🇪🇸

Madrid, Spain

Ospedale di Circolo e Fondazione Macchi

🇮🇹

Varese, Italy

Tata Memorial Hospital

🇮🇳

Mumbai, India

Hopital Regional de Sion-Herens-Conthey

🇨🇭

Sion, Switzerland

Kantonsspital - St. Gallen

🇨🇭

St. Gallen, Switzerland

Kantonsspital Winterthur

🇨🇭

Winterthur, Switzerland

Azienda Sanitaria di Bolzano

🇮🇹

Bolzano, Italy

Skaraborgs Hospital

🇸🇪

Skovde, Sweden

Brustzentrum Thurgau at Kantonsspital Frauenfeld

🇨🇭

Frauenfeld, Switzerland

Kantonsspital Baden

🇨🇭

Baden, Switzerland

Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni

🇨🇭

Bellinzona, Switzerland

Waikato Hospital

🇳🇿

Hamilton, New Zealand

Sahlgrenska University Hospital

🇸🇪

Gothenburg, Sweden

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

🇮🇹

Meldola, Italy

Hospital Clinico Universitario de Valencia

🇪🇸

Valencia, Spain

Misericordia e Dolce Hospital

🇮🇹

Prato, Italy

Osaka Rosai Hospital

🇯🇵

Sakai, Osaka, Japan

City Hospital Triemli

🇨🇭

Zurich, Switzerland

Hospital de Torrevieja

🇪🇸

Torrevieja, Spain

Regionalspital

🇨🇭

Thun, Switzerland

Malarsjukhuset Hospital

🇸🇪

Eskilstuna, Sweden

Karolinska University Hospital - Huddinge

🇸🇪

Stockholm, Sweden

Hospital Universitario Virgen Macarena

🇪🇸

Sevilla, Spain

Inselspital Bern

🇨🇭

Bern, Switzerland

Oncocare Sonnenhof-Klinik Engeriedspital

🇨🇭

Bern, Switzerland

UniversitaetsSpital Zuerich

🇨🇭

Zurich, Switzerland

Dumfries & Galloway Royal Infirmary

🇬🇧

Dumfries, Scotland, United Kingdom

European Institute of Oncology

🇮🇹

Milan, Italy

Fondazione Salvatore Maugeri

🇮🇹

Pavia, Italy

Lidkoping Hospital

🇸🇪

Lidkoping, Sweden

Kyoto University Hospital

🇯🇵

Kyoto, Japan

Bankstown - Lidcombe Hospital

🇦🇺

Bankstown, New South Wales, Australia

Breast Center

🇨🇭

Zurich, Switzerland

Southern Highlands Cancer Center

🇦🇺

Bowral, New South Wales, Australia

Port Mcquarie Base Hospital

🇦🇺

Port Macquarie, New South Wales, Australia

Prince of Wales Private Hospital

🇦🇺

Randwick, New South Wales, Australia

Tamworth Base Hospital

🇦🇺

Tamworth, New South Wales, Australia

Tweed Heads Hospital

🇦🇺

Tweed Heads, New South Wales, Australia

Calvary Mater Newcastle

🇦🇺

Waratah, New South Wales, Australia

North West Regional Hospital

🇦🇺

Burnie, Tasmania, Australia

Box Hill Hospital

🇦🇺

Box Hill, Victoria, Australia

Royal Hobart Hospital

🇦🇺

Hobart, Tasmania, Australia

Landeskrankenhaus Feldkirch

🇦🇹

Feldkirch, Austria

Maroondah Hospital

🇦🇺

Melbourne, Victoria, Australia

Peter MacCallum Cancer Centre

🇦🇺

East Melbourne, Victoria, Australia

Austin Health

🇦🇺

Heidelberg, Victoria, Australia

Royal Perth Hospital

🇦🇺

Perth, Western Australia, Australia

Krankenhaus BHS Linz

🇦🇹

Linz, Austria

Allgemeines Krankenhaus Linz

🇦🇹

Linz, Austria

LKH Villach

🇦🇹

Villach, Austria

St. Johanns-Spital

🇦🇹

Salzburg, Austria

Institut Jules Bordet

🇧🇪

Brussels, Belgium

Medizinische Universitaet Graz

🇦🇹

Graz, Austria

Medical University of Vienna

🇦🇹

Vienna, Austria

Allgemeines Krankenhaus - Universitatskliniken

🇦🇹

Vienna, Austria

Krankenhaus Lainz

🇦🇹

Vienna, Austria

Cliniques du Sud Luxembourg

🇧🇪

Arlon, Belgium

Ziekenhuis Netwerk Antwerpen Middelheim

🇧🇪

Antwerpen, Belgium

AZ Klina

🇧🇪

Brasschaat, Belgium

Cliniques Universitaires Saint-Luc

🇧🇪

Brussels, Belgium

Centre Hospitalier Universitaire Brugmann

🇧🇪

Brussels, Belgium

Algemeen Ziekenhuis Sint-Maarten - Campus Rooiberg

🇧🇪

Duffel, Belgium

Academisch Ziekenhuis der Vrije Universiteit Brussel

🇧🇪

Brussels, Belgium

Hopital de Jolimont

🇧🇪

Haine Saint Paul, Belgium

Universitair Ziekenhuis Gent

🇧🇪

Ghent, Belgium

AZ Groeninge - Oncologisch Centrum

🇧🇪

Kortrijk, Belgium

Centre Hospitalier Hutois

🇧🇪

Huy, Belgium

Centre Hospitalier Regional de la Citadelle

🇧🇪

Liege, Belgium

Centre Hospitalier de l'Ardenne

🇧🇪

Libramont, Belgium

U.Z. Gasthuisberg

🇧🇪

Leuven, Belgium

Clinique Saint-Joseph

🇧🇪

Liege, Belgium

CHU Liege - Domaine Universitaire du Sart Tilman

🇧🇪

Liege, Belgium

Clinique Saint-Pierre

🇧🇪

Ottignies, Belgium

Jan Palfijn Hospital

🇧🇪

Merksem, Belgium

AZ Damiaan

🇧🇪

Oostende, Belgium

Sint-Elisabethziekenhuis

🇧🇪

Turnhout, Belgium

Clinique Saint Vincent

🇧🇪

Rocourt, Belgium

Hospital Santiago Oriente Dr. Luis Tisne Brousse

🇨🇱

Penalolen, Chile

Centre Hospitalier Peltzer-La Tourelle

🇧🇪

Verviers, Belgium

Fundacion Arturo Lopez Perez

🇨🇱

Santiago, Chile

AZ Nikolaas - Sint-Niklaas

🇧🇪

Sint-Niklaas, Belgium

Instituto Nacional Del Cancer

🇨🇱

Santiago, Chile

Hospital Clinico San Borja Arriaran

🇨🇱

Santiago, Chile

Hospital Clinico Regional de Valdivia at University Austral de Chile

🇨🇱

Valdivia, Chile

Hillerod Hospital

🇩🇰

Hillerod, Denmark

Centralsygehus Esbjerg

🇩🇰

Esbjerg, Denmark

Herning Central Hospital

🇩🇰

Herning, Denmark

IRAM - Chile

🇨🇱

Santiago, Chile

Aarhus Universitetshospital - Aarhus Sygehus

🇩🇰

Aarhus C, Denmark

Naestved Hospital

🇩🇰

Naestved, Denmark

Hospital Carlos Van Buren

🇨🇱

Valparaiso, Chile

Copenhagen County Herlev University Hospital

🇩🇰

Copenhagen, Denmark

Odense University Hospital

🇩🇰

Odense, Denmark

Roskilde Amtssygehuset

🇩🇰

Roskilde, Denmark

Bornholms Hospital

🇩🇰

Ronne, Denmark

Sonderborg Sygehus

🇩🇰

Sonderborg, Denmark

Vejle Sygehus

🇩🇰

Vejle, Denmark

Vinzenzkrankenhaus Hannover gGmbH

🇩🇪

Hannover, Germany

Viborg Sygehus

🇩🇰

Viborg, Denmark

Institut Bergonie

🇫🇷

Bordeaux, France

Praxis Dr. Wilke - Onkologie am Klinikum Fuerth

🇩🇪

Fuerth, Germany

Onkologische Schwerpunktpraxis Bielefeld

🇩🇪

Bielefeld, Germany

Klinikum Deggendorf

🇩🇪

Deggendorf, Germany

Henriettenstiftung Krankenhaus

🇩🇪

Hannover, Germany

Aalen Breast Center

🇩🇪

Aalen, Germany

Allgemeinen Krankenhaus Celle Kinderklinik

🇩🇪

Celle, Germany

Gynaekologisch-onkologische Praxis Hannover

🇩🇪

Hannover, Germany

Gemeinschaftspraxis Gynaekologie & Geburtshilfe

🇩🇪

Mannheim, Germany

Frauenheilkunde u. Geburtshilfe

🇩🇪

Ilsede, Germany

Asklepios Klinik Lich

🇩🇪

Lich, Germany

Klinikum Meiningen GmbH

🇩🇪

Meiningen, Germany

Klinikum Offenback GmbH

🇩🇪

Offenbach, Germany

Klinikum Memmingen

🇩🇪

Memmingen, Germany

Deaconess Hospital

🇩🇪

Schwabisch Hall, Germany

Johanniter Kankenhaus Stendal

🇩🇪

Stendal, Germany

SRH Zentralklinikum Suhl GmbH

🇩🇪

Suhl, Germany

National Institute of Oncology - Budapest

🇭🇺

Budapest, Hungary

Szeged University

🇭🇺

Szeged, Hungary

Universitaetsklinikum Tuebingen

🇩🇪

Tuebingen, Germany

M. D. Anderson International Espana SA

🇪🇸

Madrid, Spain

Sandton Oncology Medical Research

🇿🇦

Sandton, South Africa

Russian Academy of Medical Sciences Cancer Research Center

🇷🇺

Moscow, Russian Federation

Hospital Universitario 12 de Octubre

🇪🇸

Madrid, Spain

Instituto Valenciano De Oncologia

🇪🇸

Valencia, Spain

Hospital Sant Joan de Reus

🇪🇸

Reus, Spain

Kantonsspital Aarau

🇨🇭

Aarau, Switzerland

Kantonsspital Graubuenden

🇨🇭

Chur, Switzerland

Kantonsspital Freiburg

🇨🇭

Freiburg, Switzerland

AndreasKlinik Cham Zug

🇨🇭

Cham, Switzerland

Lago Maggiore Oncology Foundation

🇨🇭

Locarno, Switzerland

Ospedale Civico

🇨🇭

Lugano, Switzerland

Ospedale Beata Vergine

🇨🇭

Mendrisio, Switzerland

Kantonsspital Olten

🇨🇭

Olten, Switzerland

Borders General Hospital

🇬🇧

Melrose, England, United Kingdom

Virga Jesse Hospital

🇧🇪

Hasselt, Belgium

Klinikum Kreuzschwestern Wels GmbH

🇦🇹

Wels, Austria

Imelda vzw, Ziekenhuis

🇧🇪

Bonheiden, Belgium

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