Breast CancerPhase 3SOLENCT00553410
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
A Phase 3 study testing Letrozole in people with Breast Cancer, run by ETOP IBCSG Partners Foundation at 164 sites in 20 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 120 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Letrozole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4,884 participants
- Where
- 164 sitesin 20 countries
- Study dates
- Aug 2007to 15 May 2019
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- Women only
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
164 sites in 20 countries.
164 sites in 20 countries
Belgium26 sites
Ziekenhuis Netwerk Antwerpen Middelheim
Antwerp, B-2020
Cliniques du Sud Luxembourg
Arlon, 6700
Imelda vzw, Ziekenhuis
Bonheiden, 2820
AZ Klina
Brasschaat, 2930
Institut Jules Bordet
Brussels, 1000
Academisch Ziekenhuis der Vrije Universiteit Brussel
Brussels, 1090
Cliniques Universitaires Saint-Luc
Brussels, 1200
Centre Hospitalier Universitaire Brugmann
Brussels, B 1020
Algemeen Ziekenhuis Sint-Maarten - Campus Rooiberg
Duffel, 2570
Universitair Ziekenhuis Gent
Ghent, B-9000
Hopital de Jolimont
Haine-Saint-Paul, 7100
Virga Jesse Hospital
Hasselt, 3500
Centre Hospitalier Hutois
Huy, 4500
AZ Groeninge - Oncologisch Centrum
Kortrijk, 8500
U.Z. Gasthuisberg
Leuven, B-3000
Centre Hospitalier de l'Ardenne
Libramont, 6800
Centre Hospitalier Regional de la Citadelle
Liège, 4000
Clinique Saint-Joseph
Liège, B 4000
CHU Liege - Domaine Universitaire du Sart Tilman
Liège, B-4000
Jan Palfijn Hospital
Merksem, B-2170
AZ Damiaan
Ostend, 8400
Clinique Saint-Pierre
Ottignies, B-1340
Clinique Saint Vincent
Rocourt, 4000
AZ Nikolaas - Sint-Niklaas
Sint-Niklaas, 9100
Sint-Elisabethziekenhuis
Turnhout, 2300
Centre Hospitalier Peltzer-La Tourelle
Verviers, B-4800
Switzerland23 sites
Kantonsspital Aarau
Aarau, CH-5001
Kantonsspital Baden
Baden, CH-5404
Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni
Bellinzona, CH-6500
Inselspital Bern
Bern, CH-3010
Oncocare Sonnenhof-Klinik Engeriedspital
Bern, CH-3012
AndreasKlinik Cham Zug
Cham, CH-6330
Kantonsspital Graubuenden
Chur, CH-7000
Brustzentrum Thurgau at Kantonsspital Frauenfeld
Frauenfeld, 8501
Kantonsspital Freiburg
Fribourg, 1708
Centre Hospitalier Universitaire Vaudois
Lausanne, CH-1011
Lago Maggiore Oncology Foundation
Locarno, 6600
Ospedale "la Carita", Locarno
Locarno, 6600
Ospedale Civico
Lugano, CH-6903
Ospedale Beata Vergine
Mendrisio, CH-6850
Kantonsspital Olten
Olten, CH-4600
Tumor Zentrum ZeTup St. Gallen und Chur
Sankt Gallen, CH-9006
Kantonsspital - St. Gallen
Sankt Gallen, CH-9007
Hopital Regional de Sion-Herens-Conthey
Sion, CH -1951
Regionalspital
Thun, 3600
Kantonsspital Winterthur
Winterthur, CH-8400
Breast Center
Zurich, CH-8008
City Hospital Triemli
Zurich, CH-8063
UniversitaetsSpital Zuerich
Zurich, CH-8091
Germany18 sites
Aalen Breast Center
Aalen, 73430
Onkologische Schwerpunktpraxis Bielefeld
Bielefeld, D-33602
Allgemeinen Krankenhaus Celle Kinderklinik
Celle, 29223
Klinikum Deggendorf
Deggendorf, 94469
Praxis Dr. Wilke - Onkologie am Klinikum Fuerth
Fürth, 90766
Vinzenzkrankenhaus Hannover gGmbH
Hanover, 30559
Henriettenstiftung Krankenhaus
Hanover, D-30171
Gynaekologisch-onkologische Praxis Hannover
Hanover, D-30177
Frauenheilkunde u. Geburtshilfe
Ilsede, 31241
Asklepios Klinik Lich
Lich, D-35423
Gemeinschaftspraxis Gynaekologie & Geburtshilfe
Mannheim, D68161
Klinikum Meiningen GmbH
Meiningen, 98617
Klinikum Memmingen
Memmingen, 87700
Klinikum Offenback GmbH
Offenbach, D-63069
Deaconess Hospital
Schwäbisch Hall, D-74523
Johanniter Kankenhaus Stendal
Stendal, 39576
SRH Zentralklinikum Suhl GmbH
Suhl, 98527
Universitaetsklinikum Tuebingen
Tübingen, D-72076
Australia17 sites
Armidale Hospital
Armidale, New South Wales, 2350
Bankstown - Lidcombe Hospital
Bankstown, New South Wales, 2200
Southern Highlands Cancer Center
Bowral, New South Wales, 2576
Box Hill Hospital
Box Hill, Victoria, 3128
North West Regional Hospital
Burnie, Tasmania, 7320
Concord Repatriation General Hospital
Concord, New South Wales, 2139
Peter MacCallum Cancer Centre
East Melbourne, Victoria, 3002
Breast Center
Gateshead, New South Wales, 2290
Austin Health
Heidelberg, Victoria, 3084
Royal Hobart Hospital
Hobart, Tasmania, 7000
Maroondah Hospital
Melbourne, Victoria, 3135
Royal Perth Hospital
Perth, Western Australia, 6000
Port Mcquarie Base Hospital
Port Macquarie, New South Wales, 2444
Prince of Wales Private Hospital
Randwick, New South Wales, 2031
Tamworth Base Hospital
Tamworth, New South Wales, 2340
Tweed Heads Hospital
Tweed Heads, New South Wales, 2485
Calvary Mater Newcastle
Waratah, New South Wales, 2310
Austria12 sites
Landeskrankenhaus Feldkirch
Feldkirch, A-6807
Medizinische Universitaet Graz
Graz, A-8036
Innsbruck Universitaetsklinik
Innsbruck, A-6020
Krankenhaus BHS Linz
Linz, A-4010
Allgemeines Krankenhaus Linz
Linz, A-4021
St. Johanns-Spital
Salzburg, A-5020
Medical University of Vienna
Vienna, 1090
Allgemeines Krankenhaus - Universitatskliniken
Vienna, A-1090
Krankenhaus Lainz
Vienna, A-1130
Hanusch-Krankenhaus
Vienna, A-1140
LKH Villach
Villach, 9500
Klinikum Kreuzschwestern Wels GmbH
Wels, 4600
Denmark12 sites
Aarhus Universitetshospital - Aarhus Sygehus
Aarhus C, DK-8000
Copenhagen County Herlev University Hospital
Copenhagen, DK-2730
Centralsygehus Esbjerg
Esbjerg, DK-6700
Herning Central Hospital
Herning, DK-7400
Hillerod Hospital
Hillerød, 3400
Naestved Hospital
Næstved, 4700
Odense University Hospital
Odense, DK-5000
Bornholms Hospital
Rønne, 3700
Roskilde Amtssygehuset
Roskilde, 4000
Sonderborg Sygehus
Sønderborg, 6400
Vejle Sygehus
Vejle, DK-7100
Viborg Sygehus
Viborg, 8800
Italy12 sites
Centro di Riferimento Oncologico - Aviano
Aviano, 33081
Ospedale degli Infermi - ASL 12
Biella, 13900
Azienda Sanitaria di Bolzano
Bolzano, 39100
Spedali Civili di Brescia
Brescia, 25123
A. Perrino Hospital
Brindisi, 72100
Azienda Istituti Ospitalieri
Cremona, 26100
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
Meldola, 47014
European Institute of Oncology
Milan, 20141
Fondazione Salvatore Maugeri
Pavia, I-27100
Misericordia e Dolce Hospital
Prato, 59100
Ospedale Civile Rimini
Rimini, 47900
Ospedale di Circolo e Fondazione Macchi
Varese, 21100
Spain10 sites
Vall d'Hebron University Hospital
Barcelona, 08035
M. D. Anderson International Espana SA
Madrid, 28033
Hospital Ramon y Cajal
Madrid, 28034
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Son Llatzer
Palma de Mallorca, 07198
Hospital Sant Joan de Reus
Reus, 43201
Hospital Universitario Virgen Macarena
Seville, 41009
Hospital de Torrevieja
Torrevieja, 03180
Instituto Valenciano De Oncologia
Valencia, 46009
Hospital Clinico Universitario de Valencia
Valencia, 46010
Chile7 sites
Hospital Santiago Oriente Dr. Luis Tisne Brousse
Peñalolén, 2005
Fundacion Arturo Lopez Perez
Santiago, 29
Hospital Clinico San Borja Arriaran
Santiago
Instituto Nacional Del Cancer
Santiago
IRAM - Chile
Santiago
Hospital Clinico Regional de Valdivia at University Austral de Chile
Valdivia
Hospital Carlos Van Buren
Valparaíso
Japan7 sites
Sagara Hospital
Kagoshima, Kagoshima-ken
Kumamoto University Faculty of Medical and Pharmaceutical Sciences
Kumamoto, Kumamoto, 860-8556
Kyoto University Hospital
Kyoto, Kyoto, 606-8507
Niigata Cancer Center Hospital
Niigata, Niigata, 951-8566
Yao Municipal Hospital
Osaka, Osaka, 581-0069
Osaka Rosai Hospital
Sakai, Osaka, 1179-3
Tokyo Metropolitan - Komagome Hospital
Tokyo, Tokyo, 113-8677
Sweden6 sites
Lasarettet i Boras
Borås, 501 15
Malarsjukhuset Hospital
Eskilstuna
Sahlgrenska University Hospital
Gothenburg, S-413 45
Lidkoping Hospital
Lidköping, S-53185
Skaraborgs Hospital
Skövde, 541 85
Karolinska University Hospital - Huddinge
Stockholm, S-141 86
United States2 sites
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Faulkner Hospital
Boston, Massachusetts, 02130-3400
Hungary2 sites
National Institute of Oncology - Budapest
Budapest, 1122
Szeged University
Szeged, H-6720
New Zealand2 sites
Christchurch Hospital
Christchurch, 1
Waikato Hospital
Hamilton, 2020
South Africa2 sites
Tygerberg Hospital
Cape Town, 7505
Sandton Oncology Medical Research
Sandton, 2199
United Kingdom2 sites
Dumfries & Galloway Royal Infirmary
Dumfries, Scotland, DG1 4AP
Borders General Hospital
Melrose, England, TD6 9BS
Russia1 site
Russian Academy of Medical Sciences Cancer Research Center
Moscow, 115478
About this study
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
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.
Read the 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
- Being tested
- Letrozole
- Keywords
- stage IA breast cancer, stage IB breast cancer, stage II breast cancer, stage IIIA breast cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LetrozoleDrug
Film-coated tablet, oral use, 2.5 mg Letrozole daily for 5 years continuously
LetrozoleDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Continuous letrozole | Active comparator | Continuous letrozole: 5 years continuously (2.5 mg Letrozole daily) Receives: 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 Receives: Drug: Letrozole |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 5-year estimates, reported at a median follow-up of 60 months
Secondary outcomes (3)
Overall Survival
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).
Measured: 5-year estimates, reported at a median follow-up of 60 months
Distant Recurrence-free Interval (DRFI)
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
Measured: 5-year estimates, reported at a median follow-up of 60 months
Breast Cancer-free Interval
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.
Measured: 5-year estimates, reported at a median follow-up of 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2007 (estimated)
- Study startAug 2007
- Primary completionApr 2018
- Study completion15 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 4,884 participants (actual)
Sponsor and investigators
- Lead sponsor
- ETOP IBCSG Partners Foundation
- Sponsor type
- Research network
- Collaborators
- Breast International Group
- Responsible party
- Sponsor
- Investigators
- Marco Colleoni, MD, Study chair, European Institute of Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00553410
- Sponsor's protocol ID
- IBCSG 35-07 / BIG 1-07
- Other IDs
- 2007-001370-88, CDR0000574249
- Acronym
- SOLE
- Status last verified
- May 2019
- First submitted
- 2 Nov 2007
- Last updated
- 23 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 33082214Colleoni 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.
PubMed 29158011