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

NCT ID: NCT00553410

Last Updated: 2020-03-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 4884 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-08-31
• Study Completion Date: 2019-05-15

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Continuous letrozole

Continuous letrozole: 5 years continuously (2.5 mg Letrozole daily)

Group Type: ACTIVE_COMPARATOR

Letrozole

Intervention Type: DRUG

Film-coated tablet, oral use, 2.5 mg Letrozole daily for 5 years continuously

Intermittent letrozole

Intermittent 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

Group Type: EXPERIMENTAL

Letrozole

Intervention Type: DRUG

Film-coated tablet, oral use, 2.5 mg daily, 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

Interventions

Letrozole

Film-coated tablet, oral use, 2.5 mg Letrozole daily for 5 years continuously

Intervention Type: DRUG

Letrozole

Film-coated tablet, oral use, 2.5 mg daily, 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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Clinically disease-free
• Must have completed 4-6 years of prior adjuvant selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs), or a sequential combination of both

• When calculating 4-6 years, neoadjuvant endocrine therapy should not be included
• No evidence of recurrent disease or distant metastatic disease
• No prior bilateral breast cancer

PATIENT CHARACTERISTICS:

• Female
• Must be postmenopausal by any of the following criteria:

• Patients of any age who have had a bilateral oophorectomy (including radiation castration AND amenorrheic for > 3 months)
• Patients 56 years old or older with any evidence of ovarian function must have biochemical evidence of definite postmenopausal status (defined as estradiol, luteinizing hormone [LH], and follicle-stimulating hormone [FSH] in the postmenopausal range)
• Patients 55 years old or younger must have biochemical evidence of definite postmenopausal status (defined as estradiol, LH, and FSH in the postmenopausal range)

• Patients who have received prior luteinizing-hormone releasing-hormone (LHRH) analogues within the last year are eligible if they have definite evidence of postmenopausal status as defined above
• Clinically adequate hepatic function
• No bone fracture due to osteoporosis at any time during the 4-6 years of prior therapy
• No prior or current malignancy except adequately treated basal cell or squamous cell carcinoma of the skin, in situ carcinoma of the cervix or bladder, or contra- or ipsilateral in situ breast carcinoma
• No other nonmalignant systemic diseases (cardiovascular, renal, lung, etc.) that would prevent prolonged follow-up
• No psychiatric, addictive, or any other disorder that compromises compliance with protocol requirements

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• More than 12 months since prior and no other concurrent endocrine SERM/AI therapy
• Any type of prior adjuvant therapy allowed including, but not limited to, any of the following:

• Neoadjuvant chemotherapy
• Neoadjuvant endocrine therapy
• Adjuvant chemotherapy
• Trastuzumab (Herceptin®)
• Ovarian ablation
• Gonadotropin releasing hormone analogues
• Lapatinib ditosylate
• No concurrent hormone-replacement therapy, bisphosphonates (except for treatment of bone loss), or any other investigational agent

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Breast International Group

OTHER

Sponsor Role: collaborator

ETOP IBCSG Partners Foundation

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marco Colleoni, MD

Role: STUDY_CHAIR

European Institute of Oncology

Locations

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

Boston, Massachusetts, United States

Faulkner Hospital

Boston, Massachusetts, United States

Armidale Hospital

Armidale, New South Wales, Australia

Bankstown - Lidcombe Hospital

Bankstown, New South Wales, Australia

Southern Highlands Cancer Center

Bowral, New South Wales, Australia

Concord Repatriation General Hospital

Concord, New South Wales, Australia

Breast Center

Gateshead, 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

Royal Hobart Hospital

Hobart, Tasmania, Australia

Box Hill Hospital

Box Hill, Victoria, Australia

Peter MacCallum Cancer Centre

East Melbourne, Victoria, Australia

Austin Health

Heidelberg, Victoria, Australia

Maroondah Hospital

Melbourne, Victoria, Australia

Royal Perth Hospital

Perth, Western Australia, Australia

Landeskrankenhaus Feldkirch

Feldkirch, , Austria

Medizinische Universitaet Graz

Graz, , Austria

Innsbruck Universitaetsklinik

Innsbruck, , Austria

Krankenhaus BHS Linz

Linz, , Austria

Allgemeines Krankenhaus Linz

Linz, , Austria

St. Johanns-Spital

Salzburg, , Austria

Medical University of Vienna

Vienna, , Austria

Allgemeines Krankenhaus - Universitatskliniken

Vienna, , Austria

Krankenhaus Lainz

Vienna, , Austria

Hanusch-Krankenhaus

Vienna, , Austria

LKH Villach

Villach, , Austria

Klinikum Kreuzschwestern Wels GmbH

Wels, , Austria

Ziekenhuis Netwerk Antwerpen Middelheim

Antwerp, , Belgium

Cliniques du Sud Luxembourg

Arlon, , Belgium

Imelda vzw, Ziekenhuis

Bonheiden, , Belgium

AZ Klina

Brasschaat, , Belgium

Institut Jules Bordet

Brussels, , Belgium

Academisch Ziekenhuis der Vrije Universiteit Brussel

Brussels, , Belgium

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Centre Hospitalier Universitaire Brugmann

Brussels, , Belgium

Algemeen Ziekenhuis Sint-Maarten - Campus Rooiberg

Duffel, , Belgium

Universitair Ziekenhuis Gent

Ghent, , Belgium

Hopital de Jolimont

Haine-Saint-Paul, , Belgium

Virga Jesse Hospital

Hasselt, , Belgium

Centre Hospitalier Hutois

Huy, , Belgium

AZ Groeninge - Oncologisch Centrum

Kortrijk, , Belgium

U.Z. Gasthuisberg

Leuven, , Belgium

Centre Hospitalier de l'Ardenne

Libramont, , Belgium

Centre Hospitalier Regional de la Citadelle

Liège, , Belgium

Clinique Saint-Joseph

Liège, , Belgium

CHU Liege - Domaine Universitaire du Sart Tilman

Liège, , Belgium

Jan Palfijn Hospital

Merksem, , Belgium

AZ Damiaan

Ostend, , Belgium

Clinique Saint-Pierre

Ottignies, , Belgium

Clinique Saint Vincent

Rocourt, , Belgium

AZ Nikolaas - Sint-Niklaas

Sint-Niklaas, , Belgium

Sint-Elisabethziekenhuis

Turnhout, , Belgium

Centre Hospitalier Peltzer-La Tourelle

Verviers, , Belgium

Hospital Santiago Oriente Dr. Luis Tisne Brousse

Peñalolén, , Chile

Fundacion Arturo Lopez Perez

Santiago, , Chile

Hospital Clinico San Borja Arriaran

Santiago, , Chile

Instituto Nacional Del Cancer

Santiago, , Chile

IRAM - Chile

Santiago, , Chile

Hospital Clinico Regional de Valdivia at University Austral de Chile

Valdivia, , Chile

Hospital Carlos Van Buren

Valparaíso, , Chile

Aarhus Universitetshospital - Aarhus Sygehus

Aarhus C, , Denmark

Copenhagen County Herlev University Hospital

Copenhagen, , Denmark

Centralsygehus Esbjerg

Esbjerg, , Denmark

Herning Central Hospital

Herning, , Denmark

Hillerod Hospital

Hillerød, , Denmark

Naestved Hospital

Næstved, , Denmark

Odense University Hospital

Odense, , Denmark

Roskilde Amtssygehuset

Roskilde, , Denmark

Bornholms Hospital

Rønne, , Denmark

Sonderborg Sygehus

Sønderborg, , Denmark

Vejle Sygehus

Vejle, , Denmark

Viborg Sygehus

Viborg, , Denmark

Institut Bergonie

Bordeaux, , France

Aalen Breast Center

Aalen, , Germany

Onkologische Schwerpunktpraxis Bielefeld

Bielefeld, , Germany

Allgemeinen Krankenhaus Celle Kinderklinik

Celle, , Germany

Klinikum Deggendorf

Deggendorf, , Germany

Praxis Dr. Wilke - Onkologie am Klinikum Fuerth

Fürth, , Germany

Vinzenzkrankenhaus Hannover gGmbH

Hanover, , Germany

Henriettenstiftung Krankenhaus

Hanover, , Germany

Gynaekologisch-onkologische Praxis Hannover

Hanover, , Germany

Frauenheilkunde u. Geburtshilfe

Ilsede, , Germany

Asklepios Klinik Lich

Lich, , Germany

Gemeinschaftspraxis Gynaekologie & Geburtshilfe

Mannheim, , Germany

Klinikum Meiningen GmbH

Meiningen, , Germany

Klinikum Memmingen

Memmingen, , Germany

Klinikum Offenback GmbH

Offenbach, , Germany

Deaconess Hospital

Schwäbisch Hall, , Germany

Johanniter Kankenhaus Stendal

Stendal, , Germany

SRH Zentralklinikum Suhl GmbH

Suhl, , Germany

Universitaetsklinikum Tuebingen

Tübingen, , Germany

National Institute of Oncology - Budapest

Budapest, , Hungary

Szeged University

Szeged, , Hungary

Tata Memorial Hospital

Mumbai, , India

Centro di Riferimento Oncologico - Aviano

Aviano, , Italy

Ospedale degli Infermi - ASL 12

Biella, , Italy

Azienda Sanitaria di Bolzano

Bolzano, , Italy

Spedali Civili di Brescia

Brescia, , Italy

A. Perrino Hospital

Brindisi, , Italy

Azienda Istituti Ospitalieri

Cremona, , Italy

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, , Italy

European Institute of Oncology

Milan, , Italy

Fondazione Salvatore Maugeri

Pavia, , Italy

Misericordia e Dolce Hospital

Prato, , Italy

Ospedale Civile Rimini

Rimini, , Italy

Ospedale di Circolo e Fondazione Macchi

Varese, , Italy

Osaka Rosai Hospital

Sakai, Osaka, Japan

Sagara Hospital

Kagoshima, , Japan

Kumamoto University Faculty of Medical and Pharmaceutical Sciences

Kumamoto, , Japan

Kyoto University Hospital

Kyoto, , Japan

Niigata Cancer Center Hospital

Niigata, , Japan

Yao Municipal Hospital

Osaka, , Japan

Tokyo Metropolitan - Komagome Hospital

Tokyo, , Japan

Christchurch Hospital

Christchurch, , New Zealand

Waikato Hospital

Hamilton, , New Zealand

Instituto Nacional de Enfermedades Neoplasicas

Lima, , Peru

Russian Academy of Medical Sciences Cancer Research Center

Moscow, , Russia

Tygerberg Hospital

Cape Town, , South Africa

Sandton Oncology Medical Research

Sandton, , South Africa

Vall d'Hebron University Hospital

Barcelona, , Spain

M. D. Anderson International Espana SA

Madrid, , Spain

Hospital Ramon y Cajal

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Son Llatzer

Palma de Mallorca, , Spain

Hospital Sant Joan de Reus

Reus, , Spain

Hospital Universitario Virgen Macarena

Seville, , Spain

Hospital de Torrevieja

Torrevieja, , Spain

Instituto Valenciano De Oncologia

Valencia, , Spain

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Lasarettet i Boras

Borås, , Sweden

Malarsjukhuset Hospital

Eskilstuna, , Sweden

Sahlgrenska University Hospital

Gothenburg, , Sweden

Lidkoping Hospital

Lidköping, , Sweden

Skaraborgs Hospital

Skövde, , Sweden

Karolinska University Hospital - Huddinge

Stockholm, , Sweden

Kantonsspital Aarau

Aarau, , Switzerland

Kantonsspital Baden

Baden, , Switzerland

Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni

Bellinzona, , Switzerland

Inselspital Bern

Bern, , Switzerland

Oncocare Sonnenhof-Klinik Engeriedspital

Bern, , Switzerland

AndreasKlinik Cham Zug

Cham, , Switzerland

Kantonsspital Graubuenden

Chur, , Switzerland

Brustzentrum Thurgau at Kantonsspital Frauenfeld

Frauenfeld, , Switzerland

Kantonsspital Freiburg

Fribourg, , Switzerland

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Lago Maggiore Oncology Foundation

Locarno, , Switzerland

Ospedale "la Carita", Locarno

Locarno, , Switzerland

Ospedale Civico

Lugano, , Switzerland

Ospedale Beata Vergine

Mendrisio, , Switzerland

Kantonsspital Olten

Olten, , Switzerland

Tumor Zentrum ZeTup St. Gallen und Chur

Sankt Gallen, , Switzerland

Kantonsspital - St. Gallen

Sankt Gallen, , Switzerland

Hopital Regional de Sion-Herens-Conthey

Sion, , Switzerland

Regionalspital

Thun, , Switzerland

Kantonsspital Winterthur

Winterthur, , Switzerland

Breast Center

Zurich, , Switzerland

City Hospital Triemli

Zurich, , Switzerland

UniversitaetsSpital Zuerich

Zurich, , Switzerland

Borders General Hospital

Melrose, England, United Kingdom

Dumfries & Galloway Royal Infirmary

Dumfries, Scotland, United Kingdom

Countries

United States; Australia; Austria; Belgium; Chile; Denmark; France; Germany; Hungary; India; Italy; Japan; New Zealand; Peru; Russia; South Africa; Spain; Sweden; Switzerland; United Kingdom

References

Guerini-Rocco E, Gray KP, Fumagalli C, Reforgiato MR, Leone I, Rafaniello Raviele P, Munzone E, Kammler R, Neven P, Hitre E, Jerusalem G, Simoncini E, Gombos A, Deleu I, Karlsson P, Aebi S, Chirgwin J, Di Lauro V, Thompson A, Graas MP, Barber M, Fontaine C, Loibl S, Gavila J, Kuroi K, Muller B, O'Reilly S, Di Leo A, Goldhirsch A, Viale G, Barberis M, Regan MM, Colleoni M. Genomic Aberrations and Late Recurrence in Postmenopausal Women with Hormone Receptor-positive Early Breast Cancer: Results from the SOLE Trial. Clin Cancer Res. 2021 Jan 15;27(2):504-512. doi: 10.1158/1078-0432.CCR-20-0126. Epub 2020 Oct 20.

Reference Type: DERIVED

PMID: 33082214 (View on PubMed)

Colleoni M, Luo W, Karlsson P, Chirgwin J, Aebi S, Jerusalem G, Neven P, Hitre E, Graas MP, Simoncini E, Kamby C, Thompson A, Loibl S, Gavila J, Kuroi K, Marth C, Muller B, O'Reilly S, Di Lauro V, Gombos A, Ruhstaller T, Burstein H, Ribi K, Bernhard J, Viale G, Maibach R, Rabaglio-Poretti M, Gelber RD, Coates AS, Di Leo A, Regan MM, Goldhirsch A; SOLE Investigators. Extended adjuvant intermittent letrozole versus continuous letrozole in postmenopausal women with breast cancer (SOLE): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2018 Jan;19(1):127-138. doi: 10.1016/S1470-2045(17)30715-5. Epub 2017 Nov 17.

Reference Type: DERIVED

PMID: 29158011 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2007-001370-88

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CDR0000574249

Identifier Type: REGISTRY

Identifier Source: secondary_id

IBCSG 35-07 / BIG 1-07

Identifier Type: -

Identifier Source: org_study_id