Clinical trial NCT00553410: 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
Official title: SOLE, Study of Letrozole Extension, A Phase III Trial Evaluating the Role of Continuous Letrozole Versus Intermittent Letrozole Following 4 to 6 Years of Prior Adjuvant Endocrine Therapy for Postmenopausal Women With Hormone-Receptor Positive, Node Positive Early Stage Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: stage IA breast cancer
stage IB breast cancer
stage II breast cancer
stage IIIA breast cancer
Lead sponsor: ETOP IBCSG Partners Foundation
Sponsor class: NETWORK
Collaborators: name: Breast International Group
First posted: 2007-11-04
Enrollment: 4884
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Disease-free Survival (DFS)
timeFrame: 5-year estimates, reported at a median follow-up of 60 months
Secondary outcomes:
measure: Overall Survival
timeFrame: 5-year estimates, reported at a median follow-up of 60 months
measure: Distant Recurrence-free Interval (DRFI)
timeFrame: 5-year estimates, reported at a median follow-up of 60 months
measure: Breast Cancer-free Interval
timeFrame: 5-year estimates, reported at a median follow-up of 60 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Faulkner Hospital
state: Massachusetts
city: Armidale
country: Australia
facility: Armidale Hospital
state: New South Wales
city: Bankstown
country: Australia
facility: Bankstown - Lidcombe Hospital
state: New South Wales
city: Bowral
country: Australia
facility: Southern Highlands Cancer Center
state: New South Wales
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Gateshead
country: Australia
facility: Breast Center
state: New South Wales
city: Port Macquarie
country: Australia
facility: Port Mcquarie Base Hospital
state: New South Wales
city: Randwick
country: Australia
facility: Prince of Wales Private Hospital
state: New South Wales
city: Tamworth
country: Australia
facility: Tamworth Base Hospital
state: New South Wales
city: Tweed Heads
country: Australia
facility: Tweed Heads Hospital
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Burnie
country: Australia
facility: North West Regional Hospital
state: Tasmania
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: East Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: Maroondah Hospital
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Feldkirch
country: Austria
facility: Landeskrankenhaus Feldkirch
city: Graz
country: Austria
facility: Medizinische Universitaet Graz
city: Innsbruck
country: Austria
facility: Innsbruck Universitaetsklinik
city: Linz
country: Austria
facility: Krankenhaus BHS Linz
city: Linz
country: Austria
facility: Allgemeines Krankenhaus Linz
city: Salzburg
country: Austria
facility: St. Johanns-Spital
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Vienna
country: Austria
facility: Allgemeines Krankenhaus - Universitatskliniken
city: Vienna
country: Austria
facility: Krankenhaus Lainz
city: Vienna
country: Austria
facility: Hanusch-Krankenhaus
city: Villach
country: Austria
facility: LKH Villach
city: Wels
country: Austria
facility: Klinikum Kreuzschwestern Wels GmbH
city: Antwerpen
country: Belgium
facility: Ziekenhuis Netwerk Antwerpen Middelheim
city: Arlon
country: Belgium
facility: Cliniques du Sud Luxembourg
city: Bonheiden
country: Belgium
facility: Imelda vzw, Ziekenhuis
city: Brasschaat
country: Belgium
facility: AZ Klina
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Brussels
country: Belgium
facility: Academisch Ziekenhuis der Vrije Universiteit Brussel
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Brussels
country: Belgium
facility: Centre Hospitalier Universitaire Brugmann
city: Duffel
country: Belgium
facility: Algemeen Ziekenhuis Sint-Maarten - Campus Rooiberg
city: Ghent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Haine Saint Paul
country: Belgium
facility: Hopital de Jolimont
city: Hasselt
country: Belgium
facility: Virga Jesse Hospital
city: Huy
country: Belgium
facility: Centre Hospitalier Hutois
city: Kortrijk
country: Belgium
facility: AZ Groeninge - Oncologisch Centrum
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Libramont
country: Belgium
facility: Centre Hospitalier de l'Ardenne
city: Liege
country: Belgium
facility: Centre Hospitalier Regional de la Citadelle
city: Liege
country: Belgium
facility: Clinique Saint-Joseph
city: Liege
country: Belgium
facility: CHU Liege - Domaine Universitaire du Sart Tilman
city: Merksem
country: Belgium
facility: Jan Palfijn Hospital
city: Oostende
country: Belgium
facility: AZ Damiaan
city: Ottignies
country: Belgium
facility: Clinique Saint-Pierre
city: Rocourt
country: Belgium
facility: Clinique Saint Vincent
city: Sint-Niklaas
country: Belgium
facility: AZ Nikolaas - Sint-Niklaas
city: Turnhout
country: Belgium
facility: Sint-Elisabethziekenhuis
city: Verviers
country: Belgium
facility: Centre Hospitalier Peltzer-La Tourelle
city: Penalolen
country: Chile
facility: Hospital Santiago Oriente Dr. Luis Tisne Brousse
city: Santiago
country: Chile
facility: Fundacion Arturo Lopez Perez
city: Santiago
country: Chile
facility: Hospital Clinico San Borja Arriaran
city: Santiago
country: Chile
facility: Instituto Nacional Del Cancer
city: Santiago
country: Chile
facility: IRAM - Chile
city: Valdivia
country: Chile
facility: Hospital Clinico Regional de Valdivia at University Austral de Chile
city: Valparaiso
country: Chile
facility: Hospital Carlos Van Buren
city: Aarhus C
country: Denmark
facility: Aarhus Universitetshospital - Aarhus Sygehus
city: Copenhagen
country: Denmark
facility: Copenhagen County Herlev University Hospital
city: Esbjerg
country: Denmark
facility: Centralsygehus Esbjerg
city: Herning
country: Denmark
facility: Herning Central Hospital
city: Hillerod
country: Denmark
facility: Hillerod Hospital
city: Naestved
country: Denmark
facility: Naestved Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Ronne
country: Denmark
facility: Bornholms Hospital
city: Roskilde
country: Denmark
facility: Roskilde Amtssygehuset
city: Sonderborg
country: Denmark
facility: Sonderborg Sygehus
city: Vejle
country: Denmark
facility: Vejle Sygehus
city: Viborg
country: Denmark
facility: Viborg Sygehus
city: Bordeaux
country: France
facility: Institut Bergonie
city: Aalen
country: Germany
facility: Aalen Breast Center
city: Bielefeld
country: Germany
facility: Onkologische Schwerpunktpraxis Bielefeld
city: Celle
country: Germany
facility: Allgemeinen Krankenhaus Celle Kinderklinik
city: Deggendorf
country: Germany
facility: Klinikum Deggendorf
city: Fuerth
country: Germany
facility: Praxis Dr. Wilke - Onkologie am Klinikum Fuerth
city: Hannover
country: Germany
facility: Vinzenzkrankenhaus Hannover gGmbH
city: Hannover
country: Germany
facility: Henriettenstiftung Krankenhaus
city: Hannover
country: Germany
facility: Gynaekologisch-onkologische Praxis Hannover
city: Ilsede
country: Germany
facility: Frauenheilkunde u. Geburtshilfe
city: Lich
country: Germany
facility: Asklepios Klinik Lich
city: Mannheim
country: Germany
facility: Gemeinschaftspraxis Gynaekologie & Geburtshilfe
city: Meiningen
country: Germany
facility: Klinikum Meiningen GmbH
city: Memmingen
country: Germany
facility: Klinikum Memmingen
city: Offenbach
country: Germany
facility: Klinikum Offenback GmbH
city: Schwabisch Hall
country: Germany
facility: Deaconess Hospital
city: Stendal
country: Germany
facility: Johanniter Kankenhaus Stendal
city: Suhl
country: Germany
facility: SRH Zentralklinikum Suhl GmbH
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen
city: Budapest
country: Hungary
facility: National Institute of Oncology - Budapest
city: Szeged
country: Hungary
facility: Szeged University
city: Mumbai
country: India
facility: Tata Memorial Hospital
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico - Aviano
city: Biella
country: Italy
facility: Ospedale degli Infermi - ASL 12
city: Bolzano
country: Italy
facility: Azienda Sanitaria di Bolzano
city: Brescia
country: Italy
facility: Spedali Civili di Brescia
city: Brindisi
country: Italy
facility: A. Perrino Hospital
city: Cremona
country: Italy
facility: Azienda Istituti Ospitalieri
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
city: Milan
country: Italy
facility: European Institute of Oncology
city: Pavia
country: Italy
facility: Fondazione Salvatore Maugeri
city: Prato
country: Italy
facility: Misericordia e Dolce Hospital
city: Rimini
country: Italy
facility: Ospedale Civile Rimini
city: Varese
country: Italy
facility: Ospedale di Circolo e Fondazione Macchi
city: Sakai
country: Japan
facility: Osaka Rosai Hospital
state: Osaka
city: Kagoshima
country: Japan
facility: Sagara Hospital
city: Kumamoto
country: Japan
facility: Kumamoto University Faculty of Medical and Pharmaceutical Sciences
city: Kyoto
country: Japan
facility: Kyoto University Hospital
city: Niigata
country: Japan
facility: Niigata Cancer Center Hospital
city: Osaka
country: Japan
facility: Yao Municipal Hospital
city: Tokyo
country: Japan
facility: Tokyo Metropolitan - Komagome Hospital
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Lima
country: Peru
facility: Instituto Nacional de Enfermedades Neoplasicas
city: Moscow
country: Russian Federation
facility: Russian Academy of Medical Sciences Cancer Research Center
city: Kapstadt
country: South Africa
facility: Tygerberg Hospital
city: Sandton
country: South Africa
facility: Sandton Oncology Medical Research
city: Barcelona
country: Spain
facility: Vall d'Hebron University Hospital
city: Madrid
country: Spain
facility: M. D. Anderson International Espana SA
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Palma De Mallorca
country: Spain
facility: Hospital Son Llatzer
city: Reus
country: Spain
facility: Hospital Sant Joan de Reus
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Torrevieja
country: Spain
facility: Hospital de Torrevieja
city: Valencia
country: Spain
facility: Instituto Valenciano De Oncologia
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Boras
country: Sweden
facility: Lasarettet i Boras
city: Eskilstuna
country: Sweden
facility: Malarsjukhuset Hospital
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital
city: Lidkoping
country: Sweden
facility: Lidkoping Hospital
city: Skovde
country: Sweden
facility: Skaraborgs Hospital
city: Stockholm
country: Sweden
facility: Karolinska University Hospital - Huddinge
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau
city: Baden
country: Switzerland
facility: Kantonsspital Baden
city: Bellinzona
country: Switzerland
facility: Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Bern
country: Switzerland
facility: Oncocare Sonnenhof-Klinik Engeriedspital
city: Cham
country: Switzerland
facility: AndreasKlinik Cham Zug
city: Chur
country: Switzerland
facility: Kantonsspital Graubuenden
city: Frauenfeld
country: Switzerland
facility: Brustzentrum Thurgau at Kantonsspital Frauenfeld
city: Freiburg
country: Switzerland
facility: Kantonsspital Freiburg
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Locarno
country: Switzerland
facility: Lago Maggiore Oncology Foundation
city: Locarno
country: Switzerland
facility: Ospedale "la Carita", Locarno
city: Lugano
country: Switzerland
facility: Ospedale Civico
city: Mendrisio
country: Switzerland
facility: Ospedale Beata Vergine
city: Olten
country: Switzerland
facility: Kantonsspital Olten
city: Sion
country: Switzerland
facility: Hopital Regional de Sion-Herens-Conthey
city: St. Gallen
country: Switzerland
facility: Tumor Zentrum ZeTup St. Gallen und Chur
city: St. Gallen
country: Switzerland
facility: Kantonsspital - St. Gallen
city: Thun
country: Switzerland
facility: Regionalspital
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur
city: Zurich
country: Switzerland
facility: Breast Center
city: Zurich
country: Switzerland
facility: City Hospital Triemli
city: Zurich
country: Switzerland
facility: UniversitaetsSpital Zuerich
city: Melrose
country: United Kingdom
facility: Borders General Hospital
state: England
city: Dumfries
country: United Kingdom
facility: Dumfries & Galloway Royal Infirmary
state: Scotland
Study officials:
affiliation: European Institute of Oncology
name: Marco Colleoni, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.