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

NCT00553410 | Completed Phase 3 Results DMC

• 3 other identifiers: IBCSG 35-07 / BIG 1-072007-001370-88CDR0000574249
• Study Type: interventional
• Target: 4,884
• Locations: 19 countries
• Sites: 147

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.

Conditions

Breast Cancer

Keywords

stage IA breast cancer; stage IB breast cancer; stage II breast cancer; stage IIIA breast cancer

Outcome Measures

Primary Outcomes (1)

• Disease-free Survival (DFS)

  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.

  5-year estimates, reported at a median follow-up of 60 months

Secondary Outcomes (3)

• Overall Survival

  5-year estimates, reported at a median follow-up of 60 months

• Distant Recurrence-free Interval (DRFI)

  5-year estimates, reported at a median follow-up of 60 months

• Breast Cancer-free Interval

  5-year estimates, reported at a median follow-up of 60 months

Study Arms (2)

Continuous letrozole

ACTIVE COMPARATOR

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

Drug: Letrozole

Intermittent letrozole

EXPERIMENTAL

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

Drug: Letrozole

Interventions

Letrozole DRUG

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

Continuous letrozole

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Confirmed diagnosis of prior operable, noninflammatory breast cancer meeting the following criteria: * Steroid hormone receptor-positive tumors (estrogen receptor and/or progesterone receptor), determined by immunohistochemistry, after primary surgery and before commencement of prior endocrine therapy * Prior local treatment including surgery with or without radiotherapy for primary breast cancer with no known clinical residual loco-regional disease * Following primary surgery, eligible patients must have had evidence of lymph node involvement either in the axillary or internal mammary nodes, but not supraclavicular nodes * 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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• ETOP IBCSG Partners Foundation: lead
• Breast International Group: collaborator

Study Sites (164)

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

Boston, Massachusetts, 02115, United States

Location

Faulkner Hospital

Boston, Massachusetts, 02130-3400, United States

Location

Armidale Hospital

Armidale, New South Wales, 2350, Australia

Location

Bankstown - Lidcombe Hospital

Bankstown, New South Wales, 2200, Australia

Location

Southern Highlands Cancer Center

Bowral, New South Wales, 2576, Australia

Location

Concord Repatriation General Hospital

Concord, New South Wales, 2139, Australia

Location

Breast Center

Gateshead, New South Wales, 2290, Australia

Location

Port Mcquarie Base Hospital

Port Macquarie, New South Wales, 2444, Australia

Location

Prince of Wales Private Hospital

Randwick, New South Wales, 2031, Australia

Location

Tamworth Base Hospital

Tamworth, New South Wales, 2340, Australia

Location

Tweed Heads Hospital

Tweed Heads, New South Wales, 2485, Australia

Location

Calvary Mater Newcastle

Waratah, New South Wales, 2310, Australia

Location

North West Regional Hospital

Burnie, Tasmania, 7320, Australia

Location

Royal Hobart Hospital

Hobart, Tasmania, 7000, Australia

Location

Box Hill Hospital

Box Hill, Victoria, 3128, Australia

Location

Peter MacCallum Cancer Centre

East Melbourne, Victoria, 3002, Australia

Location

Austin Health

Heidelberg, Victoria, 3084, Australia

Location

Maroondah Hospital

Melbourne, Victoria, 3135, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

Location

Landeskrankenhaus Feldkirch

Feldkirch, A-6807, Austria

Location

Medizinische Universitaet Graz

Graz, A-8036, Austria

Location

Innsbruck Universitaetsklinik

Innsbruck, A-6020, Austria

Location

Krankenhaus BHS Linz

Linz, A-4010, Austria

Location

Allgemeines Krankenhaus Linz

Linz, A-4021, Austria

Location

St. Johanns-Spital

Salzburg, A-5020, Austria

Location

Medical University of Vienna

Vienna, 1090, Austria

Location

Allgemeines Krankenhaus - Universitatskliniken

Vienna, A-1090, Austria

Location

Krankenhaus Lainz

Vienna, A-1130, Austria

Location

Hanusch-Krankenhaus

Vienna, A-1140, Austria

Location

LKH Villach

Villach, 9500, Austria

Location

Klinikum Kreuzschwestern Wels GmbH

Wels, 4600, Austria

Location

Ziekenhuis Netwerk Antwerpen Middelheim

Antwerp, B-2020, Belgium

Location

Cliniques du Sud Luxembourg

Arlon, 6700, Belgium

Location

Imelda vzw, Ziekenhuis

Bonheiden, 2820, Belgium

Location

AZ Klina

Brasschaat, 2930, Belgium

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

Academisch Ziekenhuis der Vrije Universiteit Brussel

Brussels, 1090, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

Centre Hospitalier Universitaire Brugmann

Brussels, B 1020, Belgium

Location

Algemeen Ziekenhuis Sint-Maarten - Campus Rooiberg

Duffel, 2570, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, B-9000, Belgium

Location

Hopital de Jolimont

Haine-Saint-Paul, 7100, Belgium

Location

Virga Jesse Hospital

Hasselt, 3500, Belgium

Location

Centre Hospitalier Hutois

Huy, 4500, Belgium

Location

AZ Groeninge - Oncologisch Centrum

Kortrijk, 8500, Belgium

Location

U.Z. Gasthuisberg

Leuven, B-3000, Belgium

Location

Centre Hospitalier de l'Ardenne

Libramont, 6800, Belgium

Location

Centre Hospitalier Regional de la Citadelle

Liège, 4000, Belgium

Location

Clinique Saint-Joseph

Liège, B 4000, Belgium

Location

CHU Liege - Domaine Universitaire du Sart Tilman

Liège, B-4000, Belgium

Location

Jan Palfijn Hospital

Merksem, B-2170, Belgium

Location

AZ Damiaan

Ostend, 8400, Belgium

Location

Clinique Saint-Pierre

Ottignies, B-1340, Belgium

Location

Clinique Saint Vincent

Rocourt, 4000, Belgium

Location

AZ Nikolaas - Sint-Niklaas

Sint-Niklaas, 9100, Belgium

Location

Sint-Elisabethziekenhuis

Turnhout, 2300, Belgium

Location

Centre Hospitalier Peltzer-La Tourelle

Verviers, B-4800, Belgium

Location

Hospital Santiago Oriente Dr. Luis Tisne Brousse

Peñalolén, 2005, Chile

Location

Fundacion Arturo Lopez Perez

Santiago, 29, Chile

Location

Hospital Clinico San Borja Arriaran

Santiago, Chile

Location

Instituto Nacional Del Cancer

Santiago, Chile

Location

IRAM - Chile

Santiago, Chile

Location

Hospital Clinico Regional de Valdivia at University Austral de Chile

Valdivia, Chile

Location

Hospital Carlos Van Buren

Valparaíso, Chile

Location

Aarhus Universitetshospital - Aarhus Sygehus

Aarhus C, DK-8000, Denmark

Location

Copenhagen County Herlev University Hospital

Copenhagen, DK-2730, Denmark

Location

Centralsygehus Esbjerg

Esbjerg, DK-6700, Denmark

Location

Herning Central Hospital

Herning, DK-7400, Denmark

Location

Hillerod Hospital

Hillerød, 3400, Denmark

Location

Naestved Hospital

Næstved, 4700, Denmark

Location

Odense University Hospital

Odense, DK-5000, Denmark

Location

Roskilde Amtssygehuset

Roskilde, 4000, Denmark

Location

Bornholms Hospital

Rønne, 3700, Denmark

Location

Sonderborg Sygehus

Sønderborg, 6400, Denmark

Location

Vejle Sygehus

Vejle, DK-7100, Denmark

Location

Viborg Sygehus

Viborg, 8800, Denmark

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Aalen Breast Center

Aalen, 73430, Germany

Location

Onkologische Schwerpunktpraxis Bielefeld

Bielefeld, D-33602, Germany

Location

Allgemeinen Krankenhaus Celle Kinderklinik

Celle, 29223, Germany

Location

Klinikum Deggendorf

Deggendorf, 94469, Germany

Location

Praxis Dr. Wilke - Onkologie am Klinikum Fuerth

Fürth, 90766, Germany

Location

Vinzenzkrankenhaus Hannover gGmbH

Hanover, 30559, Germany

Location

Henriettenstiftung Krankenhaus

Hanover, D-30171, Germany

Location

Gynaekologisch-onkologische Praxis Hannover

Hanover, D-30177, Germany

Location

Frauenheilkunde u. Geburtshilfe

Ilsede, 31241, Germany

Location

Asklepios Klinik Lich

Lich, D-35423, Germany

Location

Gemeinschaftspraxis Gynaekologie & Geburtshilfe

Mannheim, D68161, Germany

Location

Klinikum Meiningen GmbH

Meiningen, 98617, Germany

Location

Klinikum Memmingen

Memmingen, 87700, Germany

Location

Klinikum Offenback GmbH

Offenbach, D-63069, Germany

Location

Deaconess Hospital

Schwäbisch Hall, D-74523, Germany

Location

Johanniter Kankenhaus Stendal

Stendal, 39576, Germany

Location

SRH Zentralklinikum Suhl GmbH

Suhl, 98527, Germany

Location

Universitaetsklinikum Tuebingen

Tübingen, D-72076, Germany

Location

National Institute of Oncology - Budapest

Budapest, 1122, Hungary

Location

Szeged University

Szeged, H-6720, Hungary

Location

Tata Memorial Hospital

Mumbai, 400012, India

Location

Centro di Riferimento Oncologico - Aviano

Aviano, 33081, Italy

Location

Ospedale degli Infermi - ASL 12

Biella, 13900, Italy

Location

Azienda Sanitaria di Bolzano

Bolzano, 39100, Italy

Location

Spedali Civili di Brescia

Brescia, 25123, Italy

Location

A. Perrino Hospital

Brindisi, 72100, Italy

Location

Azienda Istituti Ospitalieri

Cremona, 26100, Italy

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, 47014, Italy

Location

European Institute of Oncology

Milan, 20141, Italy

Location

Fondazione Salvatore Maugeri

Pavia, I-27100, Italy

Location

Misericordia e Dolce Hospital

Prato, 59100, Italy

Location

Ospedale Civile Rimini

Rimini, 47900, Italy

Location

Ospedale di Circolo e Fondazione Macchi

Varese, 21100, Italy

Location

Osaka Rosai Hospital

Sakai, Osaka, 1179-3, Japan

Location

Sagara Hospital

Kagoshima, Japan

Location

Kumamoto University Faculty of Medical and Pharmaceutical Sciences

Kumamoto, 860-8556, Japan

Location

Kyoto University Hospital

Kyoto, 606-8507, Japan

Location

Niigata Cancer Center Hospital

Niigata, 951-8566, Japan

Location

Yao Municipal Hospital

Osaka, 581-0069, Japan

Location

Tokyo Metropolitan - Komagome Hospital

Tokyo, 113-8677, Japan

Location

Christchurch Hospital

Christchurch, 1, New Zealand

Location

Waikato Hospital

Hamilton, 2020, New Zealand

Location

Instituto Nacional de Enfermedades Neoplasicas

Lima, 34, Peru

Location

Russian Academy of Medical Sciences Cancer Research Center

Moscow, 115478, Russia

Location

Tygerberg Hospital

Cape Town, 7505, South Africa

Location

Sandton Oncology Medical Research

Sandton, 2199, South Africa

Location

Vall d'Hebron University Hospital

Barcelona, 08035, Spain

Location

M. D. Anderson International Espana SA

Madrid, 28033, Spain

Location

Hospital Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Son Llatzer

Palma de Mallorca, 07198, Spain

Location

Hospital Sant Joan de Reus

Reus, 43201, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Hospital de Torrevieja

Torrevieja, 03180, Spain

Location

Instituto Valenciano De Oncologia

Valencia, 46009, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Lasarettet i Boras

Borås, 501 15, Sweden

Location

Malarsjukhuset Hospital

Eskilstuna, Sweden

Location

Sahlgrenska University Hospital

Gothenburg, S-413 45, Sweden

Location

Lidkoping Hospital

Lidköping, S-53185, Sweden

Location

Skaraborgs Hospital

Skövde, 541 85, Sweden

Location

Karolinska University Hospital - Huddinge

Stockholm, S-141 86, Sweden

Location

Kantonsspital Aarau

Aarau, CH-5001, Switzerland

Location

Kantonsspital Baden

Baden, CH-5404, Switzerland

Location

Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni

Bellinzona, CH-6500, Switzerland

Location

Inselspital Bern

Bern, CH-3010, Switzerland

Location

Oncocare Sonnenhof-Klinik Engeriedspital

Bern, CH-3012, Switzerland

Location

AndreasKlinik Cham Zug

Cham, CH-6330, Switzerland

Location

Kantonsspital Graubuenden

Chur, CH-7000, Switzerland

Location

Brustzentrum Thurgau at Kantonsspital Frauenfeld

Frauenfeld, 8501, Switzerland

Location

Kantonsspital Freiburg

Fribourg, 1708, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, CH-1011, Switzerland

Location

Lago Maggiore Oncology Foundation

Locarno, 6600, Switzerland

Location

Ospedale "la Carita", Locarno

Locarno, 6600, Switzerland

Location

Ospedale Civico

Lugano, CH-6903, Switzerland

Location

Ospedale Beata Vergine

Mendrisio, CH-6850, Switzerland

Location

Kantonsspital Olten

Olten, CH-4600, Switzerland

Location

Tumor Zentrum ZeTup St. Gallen und Chur

Sankt Gallen, CH-9006, Switzerland

Location

Kantonsspital - St. Gallen

Sankt Gallen, CH-9007, Switzerland

Location

Hopital Regional de Sion-Herens-Conthey

Sion, CH -1951, Switzerland

Location

Regionalspital

Thun, 3600, Switzerland

Location

Kantonsspital Winterthur

Winterthur, CH-8400, Switzerland

Location

Breast Center

Zurich, CH-8008, Switzerland

Location

City Hospital Triemli

Zurich, CH-8063, Switzerland

Location

UniversitaetsSpital Zuerich

Zurich, CH-8091, Switzerland

Location

Borders General Hospital

Melrose, England, TD6 9BS, United Kingdom

Location

Dumfries & Galloway Royal Infirmary

Dumfries, Scotland, DG1 4AP, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 33082214 DERIVED

• 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.

  PMID: 29158011 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Letrozole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Meredith M. Regan
• Organization: International Breast Cancer Study Group (IBCSG)

mregan@jimmy.harvard.edu

+1 617 632 3012

Study Officials

• Marco Colleoni, MD

  European Institute of Oncology

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2007
• First Posted: November 5, 2007
• Study Start: August 1, 2007
• Primary Completion: April 1, 2018
• Study Completion: May 15, 2019
• Last Updated: March 11, 2020
• Results First Posted: January 29, 2019

Record last verified: 2019-05

Locations

CL (7); SE (6); RU (1); HU (2); BE (26); CH (23); IT (12); GB (2); ZA (2); DE (18); AU (12); NZ (2); US (2); DK (12); IN (1); PE (1); FR (1); JP (7); ES (10)