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

Breast Cancer Clinical Trial

— SOLE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00553410
• Other study ID #: IBCSG 35-07 / BIG 1-07
• Secondary ID: 2007-001370-88CD
• Status: Completed
• Phase: Phase 3
• Start date: August 2007
• Est. completion date: May 15, 2019

Study information

• Verified date: May 2019
• Source: International Breast Cancer Study Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

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 information / eligibility

• Status: Completed
• Enrollment: 4884
• Est. completion date: May 15, 2019
• Est. primary completion date: April 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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

Locations

Country	Name	City	State
Australia	Armidale Hospital	Armidale	New South Wales
Australia	Bankstown - Lidcombe Hospital	Bankstown	New South Wales
Australia	Southern Highlands Cancer Center	Bowral	New South Wales
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	North West Regional Hospital	Burnie	Tasmania
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	Peter MacCallum Cancer Centre	East Melbourne	Victoria
Australia	Breast Center	Gateshead	New South Wales
Australia	Austin Health	Heidelberg	Victoria
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Maroondah Hospital	Melbourne	Victoria
Australia	Royal Perth Hospital	Perth	Western Australia
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
Austria	Landeskrankenhaus Feldkirch	Feldkirch
Austria	Medizinische Universitaet Graz	Graz
Austria	Innsbruck Universitaetsklinik	Innsbruck
Austria	Allgemeines Krankenhaus Linz	Linz
Austria	Krankenhaus BHS Linz	Linz
Austria	St. Johanns-Spital	Salzburg
Austria	Allgemeines Krankenhaus - Universitatskliniken	Vienna
Austria	Hanusch-Krankenhaus	Vienna
Austria	Krankenhaus Lainz	Vienna
Austria	Medical University of Vienna	Vienna
Austria	LKH Villach	Villach
Austria	Klinikum Kreuzschwestern Wels GmbH	Wels
Belgium	Ziekenhuis Netwerk Antwerpen Middelheim	Antwerpen
Belgium	Cliniques du Sud Luxembourg	Arlon
Belgium	Imelda vzw, Ziekenhuis	Bonheiden
Belgium	AZ Klina	Brasschaat
Belgium	Academisch Ziekenhuis der Vrije Universiteit Brussel	Brussels
Belgium	Centre Hospitalier Universitaire Brugmann	Brussels
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	Institut Jules Bordet	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	Liege
Belgium	CHU Liege - Domaine Universitaire du Sart Tilman	Liege
Belgium	Clinique Saint-Joseph	Liege
Belgium	Jan Palfijn Hospital	Merksem
Belgium	AZ Damiaan	Oostende
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
Chile	Hospital Santiago Oriente Dr. Luis Tisne Brousse	Penalolen
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	Valparaiso
Denmark	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	Hillerod
Denmark	Naestved Hospital	Naestved
Denmark	Odense University Hospital	Odense
Denmark	Bornholms Hospital	Ronne
Denmark	Roskilde Amtssygehuset	Roskilde
Denmark	Sonderborg Sygehus	Sonderborg
Denmark	Vejle Sygehus	Vejle
Denmark	Viborg Sygehus	Viborg
France	Institut Bergonie	Bordeaux
Germany	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	Fuerth
Germany	Gynaekologisch-onkologische Praxis Hannover	Hannover
Germany	Henriettenstiftung Krankenhaus	Hannover
Germany	Vinzenzkrankenhaus Hannover gGmbH	Hannover
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	Schwabisch Hall
Germany	Johanniter Kankenhaus Stendal	Stendal
Germany	SRH Zentralklinikum Suhl GmbH	Suhl
Germany	Universitaetsklinikum Tuebingen	Tuebingen
Hungary	National Institute of Oncology - Budapest	Budapest
Hungary	Szeged University	Szeged
India	Tata Memorial Hospital	Mumbai
Italy	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
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	Osaka Rosai Hospital	Sakai	Osaka
Japan	Tokyo Metropolitan - Komagome Hospital	Tokyo
New Zealand	Christchurch Hospital	Christchurch
New Zealand	Waikato Hospital	Hamilton
Peru	Instituto Nacional de Enfermedades Neoplasicas	Lima
Russian Federation	Russian Academy of Medical Sciences Cancer Research Center	Moscow
South Africa	Tygerberg Hospital	Kapstadt
South Africa	Sandton Oncology Medical Research	Sandton
Spain	Vall d'Hebron University Hospital	Barcelona
Spain	Hospital Ramon y Cajal	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	M. D. Anderson International Espana SA	Madrid
Spain	Hospital Son Llatzer	Palma De Mallorca
Spain	Hospital Sant Joan de Reus	Reus
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital de Torrevieja	Torrevieja
Spain	Hospital Clinico Universitario de Valencia	Valencia
Spain	Instituto Valenciano De Oncologia	Valencia
Sweden	Lasarettet i Boras	Boras
Sweden	Malarsjukhuset Hospital	Eskilstuna
Sweden	Sahlgrenska University Hospital	Gothenburg
Sweden	Lidkoping Hospital	Lidkoping
Sweden	Skaraborgs Hospital	Skovde
Sweden	Karolinska University Hospital - Huddinge	Stockholm
Switzerland	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	Freiburg
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	Hopital Regional de Sion-Herens-Conthey	Sion
Switzerland	Kantonsspital - St. Gallen	St. Gallen
Switzerland	Tumor Zentrum ZeTup St. Gallen und Chur	St. Gallen
Switzerland	Regionalspital	Thun
Switzerland	Kantonsspital Winterthur	Winterthur
Switzerland	Breast Center	Zurich
Switzerland	City Hospital Triemli	Zurich
Switzerland	UniversitaetsSpital Zuerich	Zurich
United Kingdom	Dumfries & Galloway Royal Infirmary	Dumfries	Scotland
United Kingdom	Borders General Hospital	Melrose	England
United States	Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Faulkner Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
International Breast Cancer Study Group	Breast International Group

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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).	5-year estimates, reported at a median follow-up of 60 months
Secondary	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	5-year estimates, reported at a median follow-up of 60 months
Secondary	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.	5-year estimates, reported at a median follow-up of 60 months