ALTTO (Adjuvant Lapatinib And/Or Trastuzumab Treatment Optimisation) Study; BIG 2-06/N063D

Neoplasms, Breast Clinical Trial

— ALTTO  

Official title:

A Randomised, Multi-centre, Open-label, Phase III Study of Adjuvant Lapatinib, Trastuzumab, Their Sequence and Their Combination in Patients With HER2/ErbB2 Positive Primary Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00490139
• Other study ID #: EGF106708
• Secondary ID: CLAP016B23012006
• Status: Completed
• Phase: Phase 3
• Start date: May 16, 2007
• Est. completion date: July 1, 2021

Study information

• Verified date: July 2021
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomised, open label multi-centre phase III study comparing the activity of lapatinib alone versus trastuzumab alone versus trastuzumab followed by lapatinib versus lapatinib concomitantly with trastuzumab in the adjuvant treatment of patients with ErbB2 overexpressing and/or amplified breast cancer. Patients will be enrolled according to one of two design schemas, with Design 2 having two chemotherapy options (Design 2 and 2B), and will be randomised to one of four treatment regimens within each design schema. The primary objective of this study is to compare disease-free survival (DFS) in patients with HER2 overexpressing and/or amplified breast cancer randomised to trastuzumab for one year versus lapatinib for one year versus trastuzumab (12 or 18 weeks, according to assigned design) followed by a six-week treatment-free interval followed by lapatinib (28 or 34 weeks, according to assigned design) versus trastuzumab in combination with lapatinib for one year (52 weeks). Secondary objectives include treatment comparisons with respect to overall survival, time to recurrence, time to distant recurrence, safety and tolerability, incidence of brain metastasis, and analyses conducted separately for cohorts of patients defined by presence or absence of cMyc oncogene amplification, expression level of PTEN and presence or absence of the p95HER2 receptor. On August 18, 2011, the ALTTO Independent Data Monitoring Committee (IDMC) met to review the first planned interim analysis. The IDMC reported that the comparison of lapatinib alone versus trastuzumab alone crossed the futility boundary, indicating that the lapatinib alone arm was unlikely to meet the pre-specified criteria to demonstrate non-inferiority to trastuzumab alone with respect to disease-free survival (DFS). The IDMC also stated that the other three arms (trastuzumab alone, sequential trastuzumab/lapatinib arm and the combination arm) should continue as planned with no changes.

Other known NCT identifiers

• NCT00609024

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8382
• Est. completion date: July 1, 2021
• Est. primary completion date: December 6, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status = 1;
• Non-metastatic operable primary invasive adenocarcinoma of the breast fulfilling the

following:

1. Histologically confirmed

2. Adequately excised (exceptions: patients who have 'non-resectable' deep margin invasion are eligible provided they have had or will receive radiotherapy encompassing the region concerned; patients with histologically documented infiltration of the skin (pT4) are eligible provided they have undergone or will receive radiotherapy encompassing the tumour bed);

3. Axilla dissected; sentinel node sampling is allowed provided that axillary dissection follows confirmation of a positive sentinel node; sentinel node sampling alone is NOT acceptable after neoadjuvant chemotherapy (in patients receiving neoadjuvant chemotherapy lymph node status will be considered unknown, regardless of the results of post-chemotherapy axillary dissection);

4. Axillary node positive patient OR node negative patient with a tumour greater than or equal to 1.0 cm in greatest diameter. For clarification, isolated tumour cells (ITC) are considered pN0 and micrometastases are considered pN1

• Known hormone receptor status (ER/PgR or ER alone)
• For Designs 1 and 2: Patients must have received at least four cycles of an approved anthracycline-based (neo-) adjuvant chemotherapy regimen or listed as an exception in Table 5 of the protocol. For Design 1: Randomization must be performed no longer than 12 weeks from day 1 of the last chemotherapy cycle after obtaining a post-chemotherapy LVEF = 50. Study treatment must start no more than 14 days after randomization For Design 2: Randomization must be performed no longer than 6 weeks from day 1 of the last anthracycline-containing chemotherapy cycle after obtaining a post-anthracycline chemotherapy LVEF = 50. Study treatment must start no more than 14 days after randomization and must be concurrent with taxanes. For Design 2B: Randomisation must be performed no longer than 8 weeks from definitive surgery. Non-anthracycline platinum containing regimen (docetaxel and carboplatin) and study treatment must start concomitantly and no more than 14 days after randomisation.
• Baseline LVEF =50% measured by echocardiography or MUGA scan. For Design 1 and Design 2 - after completion of all anthracycline-based (neo-) adjuvant chemotherapy and prior to the targeted therapy(ies); for Design 2B - prior to targeted therapy(ies) and chemotherapy (docetaxel and carboplatin)
• Over expression and/or amplification of HER2 in the invasive component of the primary tumour (in case of neoadjuvant treatment, tissue sample used for HER2 testing should be collected before neoadjuvant treatment starts), according to one of the following definitions [Wolff et al 2007] and confirmed by central laboratory prior to

randomization:

• 3+ over expression by IHC (> 30% of invasive tumour cells);
• 2+ or 3+ (in 30% or less neoplastic cells) over expression by IHC AND in situ hybridization (FISH/CISH) test demonstrating HER2 gene amplification;
• HER2 gene amplification by FISH/CISH ( > 6 HER2 gene copies per nucleus, or a FISH ratio [HER2 gene copies to chromosome 17 signals] of > than 2.2.) Patients with a negative or equivocal overall result (FISH test ratio of = 2.2, = 6.0 HER2 gene copies per nucleus) and staining scores of 0, 1+, 2+ or 3+ (in 30% or less neoplastic cells) by IHC are not eligible for participation in the trial. Equivocal local results may be submitted for a final determination by the central laboratory.
• Completion of all necessary baseline laboratory and radiological investigations
• Signed written informed consent (approved by an Independent Ethics Committee (IEC) and obtained prior to any study specific screening procedures).

Exclusion Criteria:

• History of any prior (ipsi- and/or contralateral) invasive breast carcinoma;
• Past (less than 10 years) or current history of malignant neoplasms, except for curatively treated 1) basal and squamous cell carcinoma of the skin or 2) carcinoma in situ of the cervix. NOTE: Patients with a prior malignancy diagnosed greater than 10 years in the past who have been curatively treated with surgery ONLY, WITHOUT radiation therapy or systemic therapy (chemotherapy or endocrine) are eligible for the study. Patients with any prior diagnosis of breast cancer or melanoma, at any time, are excluded from this study.
• Any clinically staged T4 tumour, including inflammatory breast cancer;
• Bilateral tumours;
• This exclusion criterion has been removed as of protocol amendment 1.

NOTE: multifocal/multicentric tumours are permitted:

• If the patient is node-negative: one of the lesions must be equal or greater than 1.0 cm (sum of the lesion diameters is not acceptable) AND must have positive HER2 status centrally-confirmed;
• If patient is node-positive: lesion size does not matter BUT one of the lesions must have HER2 positivity centrally-confirmed. If several lesions are found to be HER2 positive locally, the largest lesion should be considered for central review.
• Maximum cumulative dose of doxorubicin >360mg/m² or maximum cumulative dose of epirubicin >720mg/m² or any prior anthracyclines unrelated to the present breast cancer;
• (Neo-) or adjuvant chemotherapy using peripheral stem cell or bone marrow stem cell support;
• Any prior mediastinal irradiation except internal mammary node irradiation for the present breast cancer;
• Patients with positive or suspicious internal mammary nodes identified by sentinel node technique which have not been irradiated or will not be irradiated, or patients with supraclavicular lymph node involvement (confirmed by fine needle aspirate or biopsy);
• Prior use of anti-HER2 therapy for any reason or other prior biologic or immunotherapy for breast cancer;
• Concurrent anti-cancer treatment, except hormonal therapy or radiotherapy for the present breast cancer;
• Concurrent anti-cancer treatment in another investigational trial with hormone therapy

or immunotherapy unless approved by the Executive Committee:

• Serious cardiac illness or medical conditions including but not confined to:

History of documented congestive heart failure (CHF) or systolic dysfunction (LVEF <50%); High-risk uncontrolled arrhythmias (ventricular tachycardia, high-grade AV-block, supraventricular arrhythmias which are not adequately rate-controlled); Angina pectoris requiring antianginal medication; Clinically significant valvular heart disease; Evidence of transmural infarction on ECG; Poorly controlled hypertension (e.g. systolic >180mm Hg or diastolic >100mm Hg);

• Other concurrent serious diseases that may interfere with planned treatment including severe pulmonary conditions/illness;
• Any of the following abnormal laboratory tests immediately prior to randomization:

serum total bilirubin >1.5 x upper limit of normal (ULN), in the case of known Gilbert's syndrome, a higher serum total bilirubin (<2 X ULN) is allowed; alanine amino transferase (ALAT) or aspartate amino transferase (ASAT) >2.5 x ULN; alkaline phosphatase (ALP) > 2.5 x ULN; serum creatinine >2.0 x ULN; total white blood cell count (WBC) <2.5 x 10^9/L; absolute neutrophil count <1.5 x 10^9/L; platelets <100 x 10^9/L.

• Unresolved or unstable serious adverse events from prior adjuvant chemotherapy or radiotherapy;
• Malabsorption syndrome, any disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, or persons unable to swallow oral medication. Subjects with ulcerative colitis are also excluded;
• Pregnant, lactating or women of childbearing potential without a negative pregnancy test - urine or serum - within 7 days prior to randomization, irrespective of the method of contraception used, including tubal ligation;
• Women of childbearing potential and male participants with partners of child bearing potential, including women whose last menstrual period was <12 months ago (unless surgically sterile) who are unable or unwilling to use adequate contraceptive measures during study treatment (adequate contraceptive measures: intra-uterine device, barrier method - condoms, diaphragm - also in conjunction with spermicidal jelly, or total abstinence. Oral, injectable, or implant hormonal contraceptives are not indicated in this patient population);
• Concomitant use of CYP3A4 inhibitors or inducers.

Related Conditions & MeSH terms

• Breast Neoplasms
• Neoplasms, Breast

Intervention

Drug:
• Lapatinib
Small molecule inhibitor

Biological:
• Trastuzumab
Antibody

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Berazategui	Buenos Aires
Argentina	Novartis Investigative Site	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	Novartis Investigative Site	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	Novartis Investigative Site	Ciudad Autonoma de Buenos Aires
Argentina	Novartis Investigative Site	Mendoza
Argentina	Novartis Investigative Site	Quilmes
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Santa Fe
Argentina	Novartis Investigative Site	Tucuman
Australia	Novartis Investigative Site	Adelaide	South Australia
Australia	Novartis Investigative Site	Bedford Park	South Australia
Australia	Novartis Investigative Site	Box Hill	Victoria
Australia	Novartis Investigative Site	Bunbury	Western Australia
Australia	Novartis Investigative Site	Campbelltown
Australia	Novartis Investigative Site	Camperdown	New South Wales
Australia	Novartis Investigative Site	Coffs Harbour	New South Wales
Australia	Novartis Investigative Site	Concord	New South Wales
Australia	Novartis Investigative Site	East Bentleigh	Victoria
Australia	Novartis Investigative Site	East Melbourne	Victoria
Australia	Novartis Investigative Site	Fitzroy	Victoria
Australia	Novartis Investigative Site	Footscray	Victoria
Australia	Novartis Investigative Site	Frankston	Victoria
Australia	Novartis Investigative Site	Heidelberg	Victoria
Australia	Novartis Investigative Site	Hobart	Tasmania
Australia	Novartis Investigative Site	Kingswood	New South Wales
Australia	Novartis Investigative Site	Lismore
Australia	Novartis Investigative Site	Liverpool	New South Wales
Australia	Novartis Investigative Site	Melbourne	Victoria
Australia	Novartis Investigative Site	Murdoch
Australia	Novartis Investigative Site	Nambour	Queensland
Australia	Novartis Investigative Site	Nedlands	Western Australia
Australia	Novartis Investigative Site	North Sydney	New South Wales
Australia	Novartis Investigative Site	Parkville	Victoria
Australia	Novartis Investigative Site	Port Macquarie	New South Wales
Australia	Novartis Investigative Site	Randwick	New South Wales
Australia	Novartis Investigative Site	Ringwood East	Victoria
Australia	Novartis Investigative Site	South Brisbane	Queensland
Australia	Novartis Investigative Site	Subiaco	Western Australia
Australia	Novartis Investigative Site	Taree	New South Wales
Australia	Novartis Investigative Site	Tweed Heads	New South Wales
Australia	Novartis Investigative Site	Wagga Wagga	New South Wales
Australia	Novartis Investigative Site	Waratah	New South Wales
Australia	Novartis Investigative Site	Wendouree	Victoria
Australia	Novartis Investigative Site	Westmead	New South Wales
Australia	Novartis Investigative Site	Woodville	South Australia
Australia	Novartis Investigative Site	Woolloongabba	Queensland
Austria	Novartis Investigative Site	Guessing
Austria	Novartis Investigative Site	Linz
Austria	Novartis Investigative Site	Rankweil
Austria	Novartis Investigative Site	Salzburg
Austria	Novartis Investigative Site	Steyr
Austria	Novartis Investigative Site	Vienna
Austria	Novartis Investigative Site	Villach
Austria	Novartis Investigative Site	Wien
Austria	Novartis Investigative Site	Wolfsberg
Belgium	Novartis Investigative Site	Aalst
Belgium	Novartis Investigative Site	Antwerpen
Belgium	Novartis Investigative Site	Bonheiden
Belgium	Novartis Investigative Site	Brasschaat
Belgium	Novartis Investigative Site	Brugge
Belgium	Novartis Investigative Site	Brussel
Belgium	Novartis Investigative Site	Brussels
Belgium	Novartis Investigative Site	Brussels
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Charleroi
Belgium	Novartis Investigative Site	Edegem
Belgium	Novartis Investigative Site	Genk
Belgium	Novartis Investigative Site	Gent
Belgium	Novartis Investigative Site	Haine Saint Paul
Belgium	Novartis Investigative Site	Hasselt
Belgium	Novartis Investigative Site	Huy
Belgium	Novartis Investigative Site	Kortrijk
Belgium	Novartis Investigative Site	Leuven
Belgium	Novartis Investigative Site	Liege
Belgium	Novartis Investigative Site	Mons
Belgium	Novartis Investigative Site	Namur
Belgium	Novartis Investigative Site	Roeselare
Belgium	Novartis Investigative Site	Sint-Niklaas
Belgium	Novartis Investigative Site	Tournai
Belgium	Novartis Investigative Site	Turnhout
Belgium	Novartis Investigative Site	Verviers
Belgium	Novartis Investigative Site	Wilrijk
Belgium	Novartis Investigative Site	Yvoir
Brazil	Novartis Investigative Site	Belo Horizonte	Minas Gerais
Brazil	Novartis Investigative Site	Jau	São Paulo
Brazil	Novartis Investigative Site	Porte Alegre	Rio Grande Do Sul
Brazil	Novartis Investigative Site	Porto Alegre	Rio Grande Do Sul
Brazil	Novartis Investigative Site	Porto Alegre	Rio Grande Do Sul
Brazil	Novartis Investigative Site	Porto Alegre	Rio Grande Do Sul
Brazil	Novartis Investigative Site	Porto Alegre	Rio Grande Do Sul
Brazil	Novartis Investigative Site	Porto Alegre	Rio Grande Do Sul
Brazil	Novartis Investigative Site	Porto Alegre	Rio Grande Do Sul
Brazil	Novartis Investigative Site	Rio de Janeiro
Brazil	Novartis Investigative Site	Salvador	Bahía
Brazil	Novartis Investigative Site	Santo Andre	São Paulo
Bulgaria	Novartis Investigative Site	Shumen
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Varna
Canada	Novartis Investigative Site	Barrie	Ontario
Canada	Novartis Investigative Site	Charlottetown	Prince Edward Island
Canada	Novartis Investigative Site	Kelowna	British Columbia
Canada	Novartis Investigative Site	London	Ontario
Canada	Novartis Investigative Site	Moncton	New Brunswick
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Regina	Saskatchewan
Canada	Novartis Investigative Site	Saint John	New Brunswick
Canada	Novartis Investigative Site	Saskatoon	Saskatchewan
Canada	Novartis Investigative Site	Sault Ste. Marie	Ontario
Canada	Novartis Investigative Site	Sherbrooke	Quebec
Canada	Novartis Investigative Site	St Catharines	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Vancouver	British Columbia
Chile	Novartis Investigative Site	Arica
Chile	Novartis Investigative Site	Santiago	Región Metro De Santiago
Chile	Novartis Investigative Site	Santiago	Región Metro De Santiago
Chile	Novartis Investigative Site	Santiago	Región Metro De Santiago
Chile	Novartis Investigative Site	Santiago	Región Metro De Santiago
Chile	Novartis Investigative Site	Temuco	Región De La Araucania
Chile	Novartis Investigative Site	Valdivia	Región De Los Lagos
Chile	Novartis Investigative Site	Valparaiso	Valparaíso
Chile	Novartis Investigative Site	Vina del Mar	Valparaíso
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Guangzhou	Guangdong
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Tianjin
Croatia	Novartis Investigative Site	Varazdin
Croatia	Novartis Investigative Site	Zagreb
Croatia	Novartis Investigative Site	Zagreb
Czechia	Novartis Investigative Site	Brno
Czechia	Novartis Investigative Site	Brno
Czechia	Novartis Investigative Site	Brno
Czechia	Novartis Investigative Site	Ceske Budejovice
Czechia	Novartis Investigative Site	Chomutov
Czechia	Novartis Investigative Site	Jihlava
Czechia	Novartis Investigative Site	Novy Jicin
Czechia	Novartis Investigative Site	Olomouc
Czechia	Novartis Investigative Site	Pardubice
Czechia	Novartis Investigative Site	Praha 10
Czechia	Novartis Investigative Site	Praha 2
Czechia	Novartis Investigative Site	Praha 4
Czechia	Novartis Investigative Site	Praha 5
Czechia	Novartis Investigative Site	Praha 8
Czechia	Novartis Investigative Site	Usti nad Labem
Denmark	Novartis Investigative Site	Aalborg
Denmark	Novartis Investigative Site	Arhus C
Denmark	Novartis Investigative Site	Esbjerg
Denmark	Novartis Investigative Site	Herlev
Denmark	Novartis Investigative Site	Hilleroed
Denmark	Novartis Investigative Site	Koebenhavn Oe
Denmark	Novartis Investigative Site	Naestved
Denmark	Novartis Investigative Site	Odense
Denmark	Novartis Investigative Site	Roskilde
Denmark	Novartis Investigative Site	Vejle
Denmark	Novartis Investigative Site	Viborg
Estonia	Novartis Investigative Site	Tallinn
Estonia	Novartis Investigative Site	Tartu
France	Novartis Investigative Site	ANGERS Cedex 2
France	Novartis Investigative Site	Annecy
France	Novartis Investigative Site	Avignon
France	Novartis Investigative Site	Bayonne
France	Novartis Investigative Site	Bethune
France	Novartis Investigative Site	Bordeaux
France	Novartis Investigative Site	Brive La Gaillarde
France	Novartis Investigative Site	Bron
France	Novartis Investigative Site	Caen
France	Novartis Investigative Site	Caen Cedex 05
France	Novartis Investigative Site	Clermont Ferrand
France	Novartis Investigative Site	Coudekerque Branche
France	Novartis Investigative Site	Dijon
France	Novartis Investigative Site	Dijon Cedex
France	Novartis Investigative Site	Draguignan
France	Novartis Investigative Site	Grenoble Cedex
France	Novartis Investigative Site	Grenoble Cedex 9
France	Novartis Investigative Site	Hyeres
France	Novartis Investigative Site	La Seyne Sur Mer
France	Novartis Investigative Site	Le Chesnay
France	Novartis Investigative Site	Le Havre
France	Novartis Investigative Site	Le Mans
France	Novartis Investigative Site	Lille
France	Novartis Investigative Site	Lyon
France	Novartis Investigative Site	Lyon
France	Novartis Investigative Site	Lyon
France	Novartis Investigative Site	Marseille
France	Novartis Investigative Site	Marseille Cedex 09
France	Novartis Investigative Site	Marseille cedex 5
France	Novartis Investigative Site	Metz cedex 01
France	Novartis Investigative Site	Mont de Marsan
France	Novartis Investigative Site	Montauban
France	Novartis Investigative Site	Montbeliard
France	Novartis Investigative Site	Mulhouse
France	Novartis Investigative Site	Nancy
France	Novartis Investigative Site	Nice Cedex 2
France	Novartis Investigative Site	Nimes cedex 9
France	Novartis Investigative Site	Paris Cedex 10
France	Novartis Investigative Site	Paris Cedex 14
France	Novartis Investigative Site	Paris Cedex 5
France	Novartis Investigative Site	Perigueux
France	Novartis Investigative Site	Perin Sur Mer
France	Novartis Investigative Site	Perpignan
France	Novartis Investigative Site	Reims
France	Novartis Investigative Site	Rouen
France	Novartis Investigative Site	Rouen cedex 1
France	Novartis Investigative Site	Saint Gregoire
France	Novartis Investigative Site	Saint Jean
France	Novartis Investigative Site	Saint-Cloud
France	Novartis Investigative Site	Saint-Herblain
France	Novartis Investigative Site	Saint-Martin Boulogne
France	Novartis Investigative Site	Saint-Priest en Jarez Cedex
France	Novartis Investigative Site	Strasbourg
France	Novartis Investigative Site	Strasbourg
France	Novartis Investigative Site	Toulouse
France	Novartis Investigative Site	Toulouse
France	Novartis Investigative Site	Tours cedex
France	Novartis Investigative Site	Valenciennes
France	Novartis Investigative Site	Vandoeuvre-Les-Nancy
France	Novartis Investigative Site	Villejuif Cedex
Germany	Novartis Investigative Site	Aalen	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Ansbach	Bayern
Germany	Novartis Investigative Site	Aschaffenburg	Bayern
Germany	Novartis Investigative Site	Aschersleben	Sachsen-Anhalt
Germany	Novartis Investigative Site	Augsburg	Bayern
Germany	Novartis Investigative Site	Aurich	Niedersachsen
Germany	Novartis Investigative Site	Bad Oldesloe	Schleswig-Holstein
Germany	Novartis Investigative Site	Bad Reichenhall	Bayern
Germany	Novartis Investigative Site	Bad Soden	Hessen
Germany	Novartis Investigative Site	Baden-Baden	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Bayreuth	Bayern
Germany	Novartis Investigative Site	Bergisch Gladbach	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bielefeld	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Bochum	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Bochum	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Boeblingen	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Bonn	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Bonn	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Bonn	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Brandenburg
Germany	Novartis Investigative Site	Braunschweig	Niedersachsen
Germany	Novartis Investigative Site	Bremen
Germany	Novartis Investigative Site	Bremen
Germany	Novartis Investigative Site	Bremerhaven	Bremen
Germany	Novartis Investigative Site	Celle	Niedersachsen
Germany	Novartis Investigative Site	Chemnitz	Sachsen
Germany	Novartis Investigative Site	Coburg	Bayern
Germany	Novartis Investigative Site	Cuxhaven	Niedersachsen
Germany	Novartis Investigative Site	Dachau	Bayern
Germany	Novartis Investigative Site	Deggendorf	Bayern
Germany	Novartis Investigative Site	Donauwoerth	Bayern
Germany	Novartis Investigative Site	Dresden	Sachsen
Germany	Novartis Investigative Site	Dresden	Sachsen
Germany	Novartis Investigative Site	Duesseldorf	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Duesseldorf	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Duisburg	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Ebersberg	Bayern
Germany	Novartis Investigative Site	Eggenfelden	Bayern
Germany	Novartis Investigative Site	Emmendingen	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Erfurt	Thueringen
Germany	Novartis Investigative Site	Erlangen	Bayern
Germany	Novartis Investigative Site	Eschweiler	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Essen	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Essen	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Essen	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Essen	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Esslingen	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Flensburg	Schleswig-Holstein
Germany	Novartis Investigative Site	Forchheim	Bayern
Germany	Novartis Investigative Site	Frankfurt	Hessen
Germany	Novartis Investigative Site	Frankfurt	Hessen
Germany	Novartis Investigative Site	Frankfurt	Hessen
Germany	Novartis Investigative Site	Frankfurt am Main	Hessen
Germany	Novartis Investigative Site	Freiburg	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Freising	Bayern
Germany	Novartis Investigative Site	Friedrichshafen
Germany	Novartis Investigative Site	Fuerstenwalde	Brandenburg
Germany	Novartis Investigative Site	Fuerth	Bayern
Germany	Novartis Investigative Site	Fulda	Hessen
Germany	Novartis Investigative Site	Garmisch-Partenkirchen	Bayern
Germany	Novartis Investigative Site	Geesthacht	Schleswig-Holstein
Germany	Novartis Investigative Site	Georgsmarienhuette	Niedersachsen
Germany	Novartis Investigative Site	Gera	Thueringen
Germany	Novartis Investigative Site	Goeppingen	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Goettingen	Niedersachsen
Germany	Novartis Investigative Site	Goslar	Niedersachsen
Germany	Novartis Investigative Site	Greifswald	Mecklenburg-Vorpommern
Germany	Novartis Investigative Site	Guestrow	Mecklenburg-Vorpommern
Germany	Novartis Investigative Site	Gummersbach	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Halle	Sachsen-Anhalt
Germany	Novartis Investigative Site	Halle	Sachsen-Anhalt
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hameln	Niedersachsen
Germany	Novartis Investigative Site	Hamm-Heessen	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Hanau	Hessen
Germany	Novartis Investigative Site	Hannover	Niedersachsen
Germany	Novartis Investigative Site	Hannover	Niedersachsen
Germany	Novartis Investigative Site	Hannover	Niedersachsen
Germany	Novartis Investigative Site	Heide	Schleswig-Holstein
Germany	Novartis Investigative Site	Heidelberg	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Heidelberg	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Herne	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Homburg/Saar	Saarland
Germany	Novartis Investigative Site	Hoyerswerda	Sachsen
Germany	Novartis Investigative Site	Itzehoe	Schleswig-Holstein
Germany	Novartis Investigative Site	Jena	Thueringen
Germany	Novartis Investigative Site	Karlsruhe	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Karlsruhe	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Karlsruhe	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Kassel	Hessen
Germany	Novartis Investigative Site	Kassel	Hessen
Germany	Novartis Investigative Site	Kempten	Bayern
Germany	Novartis Investigative Site	Kiel	Schleswig-Holstein
Germany	Novartis Investigative Site	Kiel	Schleswig-Holstein
Germany	Novartis Investigative Site	Koeln	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Koeln	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Koeln	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Koenigs Wusterhausen	Brandenburg
Germany	Novartis Investigative Site	Konstanz	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Krefeld	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Kronach	Bayern
Germany	Novartis Investigative Site	Landshut	Bayern
Germany	Novartis Investigative Site	Landshut	Bayern
Germany	Novartis Investigative Site	Landstuhl	Saarland
Germany	Novartis Investigative Site	Leer	Niedersachsen
Germany	Novartis Investigative Site	Leipzig	Sachsen
Germany	Novartis Investigative Site	Leipzig	Sachsen
Germany	Novartis Investigative Site	Leverkusen	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Limburg	Hessen
Germany	Novartis Investigative Site	Loerrach	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Luckenwalde	Brandenburg
Germany	Novartis Investigative Site	Ludwigsburg	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Ludwigsfelde	Brandenburg
Germany	Novartis Investigative Site	Ludwigshafen	Rheinland-Pfalz
Germany	Novartis Investigative Site	Luebeck	Schleswig-Holstein
Germany	Novartis Investigative Site	Magdeburg	Sachsen-Anhalt
Germany	Novartis Investigative Site	Magdeburg	Sachsen-Anhalt
Germany	Novartis Investigative Site	Mainz	Rheinland-Pfalz
Germany	Novartis Investigative Site	Mannheim	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Mannheim	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Marburg	Hessen
Germany	Novartis Investigative Site	Marktredwitz	Bayern
Germany	Novartis Investigative Site	Meiningen	Thueringen
Germany	Novartis Investigative Site	Memmingen	Bayern
Germany	Novartis Investigative Site	Minden	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Moenchengladbach	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Muehlhausen	Thueringen
Germany	Novartis Investigative Site	Muelheim	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Muenchen	Bayern
Germany	Novartis Investigative Site	Muenchen	Bayern
Germany	Novartis Investigative Site	Muenchen	Bayern
Germany	Novartis Investigative Site	Muenchen	Bayern
Germany	Novartis Investigative Site	Muenchen	Bayern
Germany	Novartis Investigative Site	Muenchen	Bayern
Germany	Novartis Investigative Site	Muenster	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Muenster	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Muhr	Bayern
Germany	Novartis Investigative Site	Munchen	Bayern
Germany	Novartis Investigative Site	Mutlangen	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Neumuenster	Schleswig-Holstein
Germany	Novartis Investigative Site	Neunkirchen	Saarland
Germany	Novartis Investigative Site	Nuernberg	Bayern
Germany	Novartis Investigative Site	Nuernberg	Bayern
Germany	Novartis Investigative Site	Offenbach	Hessen
Germany	Novartis Investigative Site	Oldenburg	Niedersachsen
Germany	Novartis Investigative Site	Oldenburg	Niedersachsen
Germany	Novartis Investigative Site	Olpe	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Osnabrueck	Niedersachsen
Germany	Novartis Investigative Site	Ostfildern	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Porta Westfalica	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Radebeul	Sachsen
Germany	Novartis Investigative Site	Ravensburg	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Regensburg	Bayern
Germany	Novartis Investigative Site	Rendsburg	Schleswig-Holstein
Germany	Novartis Investigative Site	Reutlingen	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Rheinfelden	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Rodewisch	Sachsen
Germany	Novartis Investigative Site	Rosenheim	Bayern
Germany	Novartis Investigative Site	Rostock	Mecklenburg-Vorpommern
Germany	Novartis Investigative Site	Rotenburg (Wuemme)	Niedersachsen
Germany	Novartis Investigative Site	Roth	Bayern
Germany	Novartis Investigative Site	Saarbruecken	Saarland
Germany	Novartis Investigative Site	Schkeuditz	Sachsen
Germany	Novartis Investigative Site	Schwaebisch Hall	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Schwandorf	Bayern
Germany	Novartis Investigative Site	Schwerin	Mecklenburg-Vorpommern
Germany	Novartis Investigative Site	Schwetzingen	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Sigmaringen	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Solingen	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Stade	Niedersachsen
Germany	Novartis Investigative Site	Stadthagen	Niedersachsen
Germany	Novartis Investigative Site	Stendal	Sachsen-Anhalt
Germany	Novartis Investigative Site	Stralsund	Mecklenburg-Vorpommern
Germany	Novartis Investigative Site	Stuttgart	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Stuttgart	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Torgau	Sachsen
Germany	Novartis Investigative Site	Traunstein	Bayern
Germany	Novartis Investigative Site	Trier	Rheinland-Pfalz
Germany	Novartis Investigative Site	Troisdorf	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Tuebingen	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Tuttlingen	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Ulm	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Vechta	Niedersachsen
Germany	Novartis Investigative Site	Velbert	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Villingen-Schwenningen	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Waldmuenchen	Bayern
Germany	Novartis Investigative Site	Weiden	Bayern
Germany	Novartis Investigative Site	Weissenfels	Sachsen-Anhalt
Germany	Novartis Investigative Site	Wesel	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Westerstede	Niedersachsen
Germany	Novartis Investigative Site	Wiesbaden	Hessen
Germany	Novartis Investigative Site	Wiesbaden	Hessen
Germany	Novartis Investigative Site	Wiesbaden	Hessen
Germany	Novartis Investigative Site	Witten	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Wuerselen	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Wuerzburg
Germany	Novartis Investigative Site	Wuppertal	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Wuppertal	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Wuppertal	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Zittau	Sachsen
Germany	Novartis Investigative Site	Zwickau	Sachsen
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Heraklion,Crete
Greece	Novartis Investigative Site	Patra
Greece	Novartis Investigative Site	Thessaloniki
Hong Kong	Novartis Investigative Site	Kowloon
Hong Kong	Novartis Investigative Site	Tuen Mun
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Gyor
Hungary	Novartis Investigative Site	Szeged
Hungary	Novartis Investigative Site	Szombathely
India	Novartis Investigative Site	Gurgaon
India	Novartis Investigative Site	Hyderabad
India	Novartis Investigative Site	Kolkatta (w.b.)
India	Novartis Investigative Site	Mangalore
India	Novartis Investigative Site	Mumbai
India	Novartis Investigative Site	Nagpur
India	Novartis Investigative Site	New Delhi
India	Novartis Investigative Site	New Delhi
India	Novartis Investigative Site	Trivandrum
Ireland	Novartis Investigative Site	Dublin
Ireland	Novartis Investigative Site	Dublin
Ireland	Novartis Investigative Site	Dublin
Ireland	Novartis Investigative Site	Galway
Ireland	Novartis Investigative Site	Limerick
Ireland	Novartis Investigative Site	Sligo
Ireland	Novartis Investigative Site	Tallaght, Dublin
Ireland	Novartis Investigative Site	Wilton, Cork
Israel	Novartis Investigative Site	Beer-Sheva
Israel	Novartis Investigative Site	Haifa
Israel	Novartis Investigative Site	Holon
Israel	Novartis Investigative Site	Jerusalem
Israel	Novartis Investigative Site	Kfar Saba
Israel	Novartis Investigative Site	Netanya
Israel	Novartis Investigative Site	Ramat Gan
Israel	Novartis Investigative Site	Rehovot
Israel	Novartis Investigative Site	Tel Aviv
Italy	Novartis Investigative Site	Alzano Lombardo (BG)	Lombardia
Italy	Novartis Investigative Site	Asti	Piemonte
Italy	Novartis Investigative Site	Avellino	Campania
Italy	Novartis Investigative Site	Aviano (PN)	Friuli-Venezia-Giulia
Italy	Novartis Investigative Site	Bergamo	Lombardia
Italy	Novartis Investigative Site	Biella	Piemonte
Italy	Novartis Investigative Site	Brescia	Lombardia
Italy	Novartis Investigative Site	Brescia	Lombardia
Italy	Novartis Investigative Site	Brindisi	Puglia
Italy	Novartis Investigative Site	Candiolo (TO)	Piemonte
Italy	Novartis Investigative Site	Carpi (MO)	Emilia-Romagna
Italy	Novartis Investigative Site	Chieti
Italy	Novartis Investigative Site	Cosenza
Italy	Novartis Investigative Site	Cremona	Lombardia
Italy	Novartis Investigative Site	Fano (Pesaro Urbino)	Marche
Italy	Novartis Investigative Site	Fermo (AP)	Marche
Italy	Novartis Investigative Site	Firenze	Toscana
Italy	Novartis Investigative Site	Firenze	Toscana
Italy	Novartis Investigative Site	Genova	Liguria
Italy	Novartis Investigative Site	Lecce	Puglia
Italy	Novartis Investigative Site	Lecco	Lombardia
Italy	Novartis Investigative Site	Lido Di Camaiore (LU)	Toscana
Italy	Novartis Investigative Site	Livorno	Toscana
Italy	Novartis Investigative Site	Lugo (Ravenna)	Emilia-Romagna
Italy	Novartis Investigative Site	Mantova	Lombardia
Italy	Novartis Investigative Site	Meldola (FC)	Emilia-Romagna
Italy	Novartis Investigative Site	Milano	Lombardia
Italy	Novartis Investigative Site	Milano	Lombardia
Italy	Novartis Investigative Site	Milano	Lombardia
Italy	Novartis Investigative Site	Monserrato (CA)	Sardegna
Italy	Novartis Investigative Site	Montepulciano (Siena	Toscana
Italy	Novartis Investigative Site	Monza	Lombardia
Italy	Novartis Investigative Site	Palermo	Sicilia
Italy	Novartis Investigative Site	Palermo	Sicilia
Italy	Novartis Investigative Site	Pavia	Lombardia
Italy	Novartis Investigative Site	Pisa	Toscana
Italy	Novartis Investigative Site	Poggibonsi (Siena)	Toscana
Italy	Novartis Investigative Site	Potenza	Basilicata
Italy	Novartis Investigative Site	Prato	Toscana
Italy	Novartis Investigative Site	Ragusa	Sicilia
Italy	Novartis Investigative Site	Ravenna	Emilia-Romagna
Italy	Novartis Investigative Site	Rimini	Emilia-Romagna
Italy	Novartis Investigative Site	Roma	Lazio
Italy	Novartis Investigative Site	Roma	Lazio
Italy	Novartis Investigative Site	Roma	Lazio
Italy	Novartis Investigative Site	Rozzano (MI)	Lombardia
Italy	Novartis Investigative Site	San Fermo Della Battaglia (Co)	Lombardia
Italy	Novartis Investigative Site	Saronno (VA)	Lombardia
Italy	Novartis Investigative Site	Sassari	Sardegna
Italy	Novartis Investigative Site	Trento	Trentino-Alto Adige
Italy	Novartis Investigative Site	Treviglio (BG)	Lombardia
Italy	Novartis Investigative Site	Udine	Friuli-Venezia-Giulia
Italy	Novartis Investigative Site	Varese	Lombardia
Italy	Novartis Investigative Site	Viterbo	Lazio
Japan	Novartis Investigative Site	Aichi
Japan	Novartis Investigative Site	Chiba
Japan	Novartis Investigative Site	Ehime
Japan	Novartis Investigative Site	Fukuoka
Japan	Novartis Investigative Site	Ibaraki
Japan	Novartis Investigative Site	Kanagawa
Japan	Novartis Investigative Site	Kyoto
Japan	Novartis Investigative Site	Osaka
Japan	Novartis Investigative Site	Osaka
Japan	Novartis Investigative Site	Saitama
Japan	Novartis Investigative Site	Tokyo
Japan	Novartis Investigative Site	Tokyo
Japan	Novartis Investigative Site	Tokyo
Japan	Novartis Investigative Site	Tokyo
Japan	Novartis Investigative Site	Tokyo
Korea, Republic of	Novartis Investigative Site	Gyeonggi-do
Korea, Republic of	Novartis Investigative Site	Incheon
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Suwon-si, Gyeonggi-do
Malaysia	Novartis Investigative Site	Kubang Kerian
Malaysia	Novartis Investigative Site	Sarawak
Mexico	Novartis Investigative Site	Chihuahua
Mexico	Novartis Investigative Site	Merida	Yucatán
Mexico	Novartis Investigative Site	Mexico City
Mexico	Novartis Investigative Site	Mexico D.F.
Mexico	Novartis Investigative Site	Mexico DF
Mexico	Novartis Investigative Site	Toluca	Estado De México
Netherlands	Novartis Investigative Site	Amersfoort
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Arnhem
Netherlands	Novartis Investigative Site	Blaricum
Netherlands	Novartis Investigative Site	Delft
Netherlands	Novartis Investigative Site	Den Haag
Netherlands	Novartis Investigative Site	Den Haag
Netherlands	Novartis Investigative Site	Eindhoven
Netherlands	Novartis Investigative Site	Gouda
Netherlands	Novartis Investigative Site	Hoofddorp
Netherlands	Novartis Investigative Site	Leeuwarden
Netherlands	Novartis Investigative Site	Leiden
Netherlands	Novartis Investigative Site	Leidschendam
Netherlands	Novartis Investigative Site	Purmerend
Netherlands	Novartis Investigative Site	Rotterdam
Netherlands	Novartis Investigative Site	Rotterdam
Netherlands	Novartis Investigative Site	Sittard-geleen
Netherlands	Novartis Investigative Site	Tilburg
Netherlands	Novartis Investigative Site	Utrecht
New Zealand	Novartis Investigative Site	Hamilton
New Zealand	Novartis Investigative Site	Palmerston North
New Zealand	Novartis Investigative Site	Wellington
Norway	Novartis Investigative Site	Forde
Norway	Novartis Investigative Site	Oslo
Norway	Novartis Investigative Site	Oslo
Norway	Novartis Investigative Site	Tromso
Pakistan	Novartis Investigative Site	Karachi
Pakistan	Novartis Investigative Site	Karachi
Pakistan	Novartis Investigative Site	Lahore
Pakistan	Novartis Investigative Site	Lahore
Pakistan	Novartis Investigative Site	Rawalpindi
Peru	Novartis Investigative Site	Callao
Peru	Novartis Investigative Site	Lima
Peru	Novartis Investigative Site	Lima
Peru	Novartis Investigative Site	Lima
Philippines	Novartis Investigative Site	Cebu
Philippines	Novartis Investigative Site	Quezon City
Philippines	Novartis Investigative Site	Sampaloc Manila
Philippines	Novartis Investigative Site	San Juan
Poland	Novartis Investigative Site	Bydgoszcz
Poland	Novartis Investigative Site	Elblag
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Gliwice
Poland	Novartis Investigative Site	Krakow
Poland	Novartis Investigative Site	Krakow
Poland	Novartis Investigative Site	Olsztyn
Poland	Novartis Investigative Site	Olsztyn
Poland	Novartis Investigative Site	Opole
Poland	Novartis Investigative Site	Rzeszow
Poland	Novartis Investigative Site	Szczecin
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Wroclaw
Romania	Novartis Investigative Site	Bucharest
Romania	Novartis Investigative Site	Bucharest
Romania	Novartis Investigative Site	Bucuresti
Romania	Novartis Investigative Site	Cluj-Napoca
Romania	Novartis Investigative Site	Iasi
Russian Federation	Novartis Investigative Site	Arkhangelsk
Russian Federation	Novartis Investigative Site	Chelyabinsk
Russian Federation	Novartis Investigative Site	Irkutsk
Russian Federation	Novartis Investigative Site	Kazan
Russian Federation	Novartis Investigative Site	Kirov
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Novosibirsk
Russian Federation	Novartis Investigative Site	Omsk
Russian Federation	Novartis Investigative Site	Orenburg
Russian Federation	Novartis Investigative Site	Ryazan
Russian Federation	Novartis Investigative Site	Samara
Russian Federation	Novartis Investigative Site	St. Petersburg
Russian Federation	Novartis Investigative Site	St. Petersburg
Russian Federation	Novartis Investigative Site	Voronezh
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Kosice
Slovakia	Novartis Investigative Site	Poprad
Slovakia	Novartis Investigative Site	Rimavska Sobota
Slovakia	Novartis Investigative Site	Zilina
Slovenia	Novartis Investigative Site	Ljubljana
South Africa	Novartis Investigative Site	Capital Park
South Africa	Novartis Investigative Site	Groenkloof, Pretoria, 0001
South Africa	Novartis Investigative Site	Johannesburg
South Africa	Novartis Investigative Site	Observatory
South Africa	Novartis Investigative Site	Panorama
South Africa	Novartis Investigative Site	Parktown
South Africa	Novartis Investigative Site	Pretoria
South Africa	Novartis Investigative Site	Pretoria
South Africa	Novartis Investigative Site	Saxonwold, Johannesburg
Spain	Novartis Investigative Site	Alcoy/Alicante
Spain	Novartis Investigative Site	Barakaldo (Vizcaya)
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Burgos
Spain	Novartis Investigative Site	Cadiz
Spain	Novartis Investigative Site	Castellon
Spain	Novartis Investigative Site	Cordoba
Spain	Novartis Investigative Site	Coria
Spain	Novartis Investigative Site	Elda
Spain	Novartis Investigative Site	Granada
Spain	Novartis Investigative Site	Hospitalet de Llobregat (Barcelona)
Spain	Novartis Investigative Site	Huesca
Spain	Novartis Investigative Site	La Laguna (Santa Cruz De Tenerife)
Spain	Novartis Investigative Site	Lerida
Spain	Novartis Investigative Site	Lugo
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Malaga
Spain	Novartis Investigative Site	Mataro
Spain	Novartis Investigative Site	Mostoles (Madrid)
Spain	Novartis Investigative Site	Murcia
Spain	Novartis Investigative Site	Murcia
Spain	Novartis Investigative Site	Palma de Mallorca
Spain	Novartis Investigative Site	Palma de Mallorca
Spain	Novartis Investigative Site	Pamplona
Spain	Novartis Investigative Site	Salamanca
Spain	Novartis Investigative Site	San Sebastian
Spain	Novartis Investigative Site	Santander
Spain	Novartis Investigative Site	Santiago
Spain	Novartis Investigative Site	Segovia
Spain	Novartis Investigative Site	Sevilla
Spain	Novartis Investigative Site	Sevilla
Spain	Novartis Investigative Site	Tarrasa, Barcelona
Spain	Novartis Investigative Site	Toledo
Spain	Novartis Investigative Site	Valencia
Spain	Novartis Investigative Site	Valencia
Spain	Novartis Investigative Site	Zamora
Spain	Novartis Investigative Site	Zaragoza
Switzerland	Novartis Investigative Site	Aarau
Switzerland	Novartis Investigative Site	Basel
Switzerland	Novartis Investigative Site	Bellinzona
Switzerland	Novartis Investigative Site	Bern
Switzerland	Novartis Investigative Site	Chur
Switzerland	Novartis Investigative Site	Lausanne
Switzerland	Novartis Investigative Site	Locarno
Switzerland	Novartis Investigative Site	St Gallen
Switzerland	Novartis Investigative Site	Thun
Switzerland	Novartis Investigative Site	Zuerich
Switzerland	Novartis Investigative Site	Zurich
Taiwan	Novartis Investigative Site	Kaohsiung
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Tainan County
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Chiangmai
Thailand	Novartis Investigative Site	Hatyai, Songkhla
Thailand	Novartis Investigative Site	Khon Kaen
Thailand	Novartis Investigative Site	Phitsanulok
Ukraine	Novartis Investigative Site	Chernivtsi
Ukraine	Novartis Investigative Site	Donetsk
Ukraine	Novartis Investigative Site	Ivano-Frankivsk
Ukraine	Novartis Investigative Site	Kharkiv
Ukraine	Novartis Investigative Site	Kyiv
Ukraine	Novartis Investigative Site	Lviv
Ukraine	Novartis Investigative Site	Simferopol
Ukraine	Novartis Investigative Site	Uzhgorod
Ukraine	Novartis Investigative Site	Uzhorod
United Kingdom	Novartis Investigative Site	Ashford
United Kingdom	Novartis Investigative Site	Blackpool
United Kingdom	Novartis Investigative Site	Bournemouth
United Kingdom	Novartis Investigative Site	Brighton
United Kingdom	Novartis Investigative Site	Canterbury	Kent
United Kingdom	Novartis Investigative Site	Chelmsford	Essex
United Kingdom	Novartis Investigative Site	Cheltenham
United Kingdom	Novartis Investigative Site	Cottingham
United Kingdom	Novartis Investigative Site	Dorchester
United Kingdom	Novartis Investigative Site	Edinburgh	Midlothian
United Kingdom	Novartis Investigative Site	Epping	Essex
United Kingdom	Novartis Investigative Site	Exeter
United Kingdom	Novartis Investigative Site	Grimsby
United Kingdom	Novartis Investigative Site	Guildford
United Kingdom	Novartis Investigative Site	Gwynedd
United Kingdom	Novartis Investigative Site	Headington, Oxford	Oxfordshire
United Kingdom	Novartis Investigative Site	Ipswich
United Kingdom	Novartis Investigative Site	Lancaster
United Kingdom	Novartis Investigative Site	Leeds
United Kingdom	Novartis Investigative Site	Lindley, Huddersfield
United Kingdom	Novartis Investigative Site	Liverpool
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Maidstone
United Kingdom	Novartis Investigative Site	Manchester	Lancashire
United Kingdom	Novartis Investigative Site	Margate
United Kingdom	Novartis Investigative Site	Newcastle upon Tyne
United Kingdom	Novartis Investigative Site	Northwood	Middlesex
United Kingdom	Novartis Investigative Site	Nottingham	Gloucestershire
United Kingdom	Novartis Investigative Site	Nottingham
United Kingdom	Novartis Investigative Site	Plymouth
United Kingdom	Novartis Investigative Site	Poole, Dorset
United Kingdom	Novartis Investigative Site	Portsmouth
United Kingdom	Novartis Investigative Site	Preston	Lancashire
United Kingdom	Novartis Investigative Site	Prittlewell Chase	Essex
United Kingdom	Novartis Investigative Site	Romford
United Kingdom	Novartis Investigative Site	Sheffield
United Kingdom	Novartis Investigative Site	Shrewsbury
United Kingdom	Novartis Investigative Site	Southport
United Kingdom	Novartis Investigative Site	St Helens
United Kingdom	Novartis Investigative Site	Stoke on Trent
United Kingdom	Novartis Investigative Site	Sutton
United Kingdom	Novartis Investigative Site	Swansea
United Kingdom	Novartis Investigative Site	Whitchurch, Cardiff
United Kingdom	Novartis Investigative Site	Worthing
United States	Novartis Investigative Site	'Aiea	Hawaii
United States	Novartis Investigative Site	Aberdeen	South Dakota
United States	Novartis Investigative Site	Abilene	Texas
United States	Novartis Investigative Site	Abington	Pennsylvania
United States	Novartis Investigative Site	Adrian	Michigan
United States	Novartis Investigative Site	Albert Lea	Minnesota
United States	Novartis Investigative Site	Albuquerque	New Mexico
United States	Novartis Investigative Site	Albuquerque	New Mexico
United States	Novartis Investigative Site	Alexandria	Minnesota
United States	Novartis Investigative Site	Alton	Illinois
United States	Novartis Investigative Site	Amarillo	Texas
United States	Novartis Investigative Site	Ames	Iowa
United States	Novartis Investigative Site	Anchorage	Alaska
United States	Novartis Investigative Site	Anderson	South Carolina
United States	Novartis Investigative Site	Ann Arbor	Michigan
United States	Novartis Investigative Site	Ann Arbor	Michigan
United States	Novartis Investigative Site	Ann Arbor	Michigan
United States	Novartis Investigative Site	Anthony	Kansas
United States	Novartis Investigative Site	Athens	Georgia
United States	Novartis Investigative Site	Atlanta	Georgia
United States	Novartis Investigative Site	Atlanta	Georgia
United States	Novartis Investigative Site	Auburn	Washington
United States	Novartis Investigative Site	Augusta	Georgia
United States	Novartis Investigative Site	Augusta	Georgia
United States	Novartis Investigative Site	Aurora	Colorado
United States	Novartis Investigative Site	Aurora	Illinois
United States	Novartis Investigative Site	Austell	Georgia
United States	Novartis Investigative Site	Austin	Texas
United States	Novartis Investigative Site	Austin	Texas
United States	Novartis Investigative Site	Austin	Texas
United States	Novartis Investigative Site	Austin	Texas
United States	Novartis Investigative Site	Baltimore	Maryland
United States	Novartis Investigative Site	Baltimore	Maryland
United States	Novartis Investigative Site	Baton Rouge	Louisiana
United States	Novartis Investigative Site	Baton Rouge	Louisiana
United States	Novartis Investigative Site	Battle Creek	Michigan
United States	Novartis Investigative Site	Beachwood	Ohio
United States	Novartis Investigative Site	Beaumont	Texas
United States	Novartis Investigative Site	Bedford	Texas
United States	Novartis Investigative Site	Beech Grove	Indiana
United States	Novartis Investigative Site	Bellefontaine	Ohio
United States	Novartis Investigative Site	Bellingham	Washington
United States	Novartis Investigative Site	Bemidji	Minnesota
United States	Novartis Investigative Site	Berkeley	California
United States	Novartis Investigative Site	Berlin	Vermont
United States	Novartis Investigative Site	Berwyn	Illinois
United States	Novartis Investigative Site	Bethesda	Maryland
United States	Novartis Investigative Site	Bethlehem	Pennsylvania
United States	Novartis Investigative Site	Bettendorf	Iowa
United States	Novartis Investigative Site	Big Rapids	Michigan
United States	Novartis Investigative Site	Billings	Montana
United States	Novartis Investigative Site	Bismarck	North Dakota
United States	Novartis Investigative Site	Bloomington	Illinois
United States	Novartis Investigative Site	Boca Raton	Florida
United States	Novartis Investigative Site	Boise	Idaho
United States	Novartis Investigative Site	Boise	Idaho
United States	Novartis Investigative Site	Bolivar	Missouri
United States	Novartis Investigative Site	Boston	Massachusetts
United States	Novartis Investigative Site	Boston	Massachusetts
United States	Novartis Investigative Site	Boston	Massachusetts
United States	Novartis Investigative Site	Boston	Massachusetts
United States	Novartis Investigative Site	Boulder	Colorado
United States	Novartis Investigative Site	Bowling Green	Ohio
United States	Novartis Investigative Site	Bozeman	Montana
United States	Novartis Investigative Site	Bremerton	Washington
United States	Novartis Investigative Site	Bronx	New York
United States	Novartis Investigative Site	Bronx	New York
United States	Novartis Investigative Site	Bronx	New York
United States	Novartis Investigative Site	Bryn Mawr	Pennsylvania
United States	Novartis Investigative Site	Buffalo	New York
United States	Novartis Investigative Site	Burien	Washington
United States	Novartis Investigative Site	Burlingame	California
United States	Novartis Investigative Site	Burlington	Massachusetts
United States	Novartis Investigative Site	Burlington	Vermont
United States	Novartis Investigative Site	Burnsville	Minnesota
United States	Novartis Investigative Site	Butler	Pennsylvania
United States	Novartis Investigative Site	Butte	Montana
United States	Novartis Investigative Site	Byron Center	Michigan
United States	Novartis Investigative Site	Canton	Illinois
United States	Novartis Investigative Site	Canton	Ohio
United States	Novartis Investigative Site	Canton	Ohio
United States	Novartis Investigative Site	Cape Girardeau	Missouri
United States	Novartis Investigative Site	Cape Girardeau	Missouri
United States	Novartis Investigative Site	Carthage	Illinois
United States	Novartis Investigative Site	Casper	Wyoming
United States	Novartis Investigative Site	Castro Valley	California
United States	Novartis Investigative Site	Cedar Park	Texas
United States	Novartis Investigative Site	Cedar Rapids	Iowa
United States	Novartis Investigative Site	Cedar Rapids	Iowa
United States	Novartis Investigative Site	Centralia	Washington
United States	Novartis Investigative Site	Chanute	Kansas
United States	Novartis Investigative Site	Chapel Hill	North Carolina
United States	Novartis Investigative Site	Charleston	South Carolina
United States	Novartis Investigative Site	Charleston	West Virginia
United States	Novartis Investigative Site	Charlottesville	Virginia
United States	Novartis Investigative Site	Chattanooga	Tennessee
United States	Novartis Investigative Site	Chattanooga	Tennessee
United States	Novartis Investigative Site	Chicago	Illinois
United States	Novartis Investigative Site	Chicago	Illinois
United States	Novartis Investigative Site	Chillicothe	Ohio
United States	Novartis Investigative Site	Chippewa Falls	Wisconsin
United States	Novartis Investigative Site	Cincinnati	Ohio
United States	Novartis Investigative Site	Cincinnati	Ohio
United States	Novartis Investigative Site	Cleveland	Ohio
United States	Novartis Investigative Site	Cleveland	Ohio
United States	Novartis Investigative Site	Clifton Springs	New York
United States	Novartis Investigative Site	Clyde	Ohio
United States	Novartis Investigative Site	Colorado Springs	Colorado
United States	Novartis Investigative Site	Columbia	Ohio
United States	Novartis Investigative Site	Columbia	South Carolina
United States	Novartis Investigative Site	Columbus	Ohio
United States	Novartis Investigative Site	Columbus	Ohio
United States	Novartis Investigative Site	Columbus	Ohio
United States	Novartis Investigative Site	Columbus	Ohio
United States	Novartis Investigative Site	Columbus	Ohio
United States	Novartis Investigative Site	Columbus	Georgia
United States	Novartis Investigative Site	Concord	New Hampshire
United States	Novartis Investigative Site	Coon Rapids	Minnesota
United States	Novartis Investigative Site	Cooperstown	New York
United States	Novartis Investigative Site	Coos Bay	Oregon
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Danville	Pennsylvania
United States	Novartis Investigative Site	Danville	Virginia
United States	Novartis Investigative Site	Dayton	Ohio
United States	Novartis Investigative Site	Dayton	Ohio
United States	Novartis Investigative Site	Dayton	Ohio
United States	Novartis Investigative Site	Dayton	Ohio
United States	Novartis Investigative Site	Dayton	Ohio
United States	Novartis Investigative Site	Dearborn	Michigan
United States	Novartis Investigative Site	Decatur	Georgia
United States	Novartis Investigative Site	Delaware	Ohio
United States	Novartis Investigative Site	Denver	Colorado
United States	Novartis Investigative Site	Denver	Colorado
United States	Novartis Investigative Site	Denver	Colorado
United States	Novartis Investigative Site	Denver	Colorado
United States	Novartis Investigative Site	Denver	Colorado
United States	Novartis Investigative Site	Denver	Colorado
United States	Novartis Investigative Site	Des Moines	Iowa
United States	Novartis Investigative Site	Des Moines	Iowa
United States	Novartis Investigative Site	Des Moines	Iowa
United States	Novartis Investigative Site	Des Moines	Iowa
United States	Novartis Investigative Site	Detroit	Michigan
United States	Novartis Investigative Site	Detroit	Michigan
United States	Novartis Investigative Site	Dodge City	Kansas
United States	Novartis Investigative Site	Dover	Delaware
United States	Novartis Investigative Site	Duarte	California
United States	Novartis Investigative Site	Duluth	Minnesota
United States	Novartis Investigative Site	East Syracuse	New York
United States	Novartis Investigative Site	Easton	Maryland
United States	Novartis Investigative Site	Eau Claire	Wisconsin
United States	Novartis Investigative Site	Eau Claire	Wisconsin
United States	Novartis Investigative Site	Edina	Minnesota
United States	Novartis Investigative Site	Edwards	Colorado
United States	Novartis Investigative Site	El Dorado	Kansas
United States	Novartis Investigative Site	Elkhart	Indiana
United States	Novartis Investigative Site	Elmhurst	New York
United States	Novartis Investigative Site	Elyria	Ohio
United States	Novartis Investigative Site	Englewood	Colorado
United States	Novartis Investigative Site	Ephrata	Pennsylvania
United States	Novartis Investigative Site	Escanaba	Michigan
United States	Novartis Investigative Site	Eugene	Oregon
United States	Novartis Investigative Site	Eureka	Illinois
United States	Novartis Investigative Site	Evanston	Illinois
United States	Novartis Investigative Site	Exeter	New Hampshire
United States	Novartis Investigative Site	Fairbanks	Alaska
United States	Novartis Investigative Site	Fairfield	California
United States	Novartis Investigative Site	Fargo	North Dakota
United States	Novartis Investigative Site	Fayetteville	North Carolina
United States	Novartis Investigative Site	Federal Way	Washington
United States	Novartis Investigative Site	Fergus Falls	Minnesota
United States	Novartis Investigative Site	Findlay	Ohio
United States	Novartis Investigative Site	Flint	Michigan
United States	Novartis Investigative Site	Flint	Michigan
United States	Novartis Investigative Site	Fort Collins	Colorado
United States	Novartis Investigative Site	Fort Collins	Colorado
United States	Novartis Investigative Site	Fort Gordon	Georgia
United States	Novartis Investigative Site	Fort Lauderdale	Florida
United States	Novartis Investigative Site	Fort Myers	Florida
United States	Novartis Investigative Site	Fort Sam Houston	Texas
United States	Novartis Investigative Site	Fort Scott	Kansas
United States	Novartis Investigative Site	Fort Wayne	Indiana
United States	Novartis Investigative Site	Fort Worth	Texas
United States	Novartis Investigative Site	Franklin	Tennessee
United States	Novartis Investigative Site	Franklin	Ohio
United States	Novartis Investigative Site	Frederick	Maryland
United States	Novartis Investigative Site	Fredericksburg	Virginia
United States	Novartis Investigative Site	Fremont	California
United States	Novartis Investigative Site	Fresno	California
United States	Novartis Investigative Site	Fridley	Minnesota
United States	Novartis Investigative Site	Gainesville	Georgia
United States	Novartis Investigative Site	Galesburg	Illinois
United States	Novartis Investigative Site	Gastonia	North Carolina
United States	Novartis Investigative Site	Germantown	Tennessee
United States	Novartis Investigative Site	Glendale	California
United States	Novartis Investigative Site	Glenwood Springs	Colorado
United States	Novartis Investigative Site	Gloucester	Massachusetts
United States	Novartis Investigative Site	Goldsboro	North Carolina
United States	Novartis Investigative Site	Grand Forks	North Dakota
United States	Novartis Investigative Site	Grand Island	Nebraska
United States	Novartis Investigative Site	Grand Junction	Colorado
United States	Novartis Investigative Site	Grand Rapids	Michigan
United States	Novartis Investigative Site	Great Falls	Montana
United States	Novartis Investigative Site	Greeley	Colorado
United States	Novartis Investigative Site	Green Bay	Wisconsin
United States	Novartis Investigative Site	Green Bay	Wisconsin
United States	Novartis Investigative Site	Greenbrae	California
United States	Novartis Investigative Site	Greenville	Ohio
United States	Novartis Investigative Site	Greenville	South Carolina
United States	Novartis Investigative Site	Gresham	Oregon
United States	Novartis Investigative Site	Hackensack	New Jersey
United States	Novartis Investigative Site	Hagerstown	Maryland
United States	Novartis Investigative Site	Hamilton	New Jersey
United States	Novartis Investigative Site	Hampton	Virginia
* Note: There are 1412 locations in all - only the first 1000 are shown.

Sponsors (5)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals	Breast International Group, Canadian Cancer Trials Group, National Cancer Institute (NCI), North Central Cancer Treatment Group

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  Chile,  China,  Croatia,  Czechia,  Denmark,  Estonia,  France,  Germany,  Greece,  Hong Kong,  Hungary,  India,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Mexico,  Netherlands,  New Zealand,  Norway,  Pakistan,  Peru,  Philippines,  Poland,  Romania,  Russian Federation,  Singapore,  Slovakia,  Slovenia,  South Africa,  Spain,  Switzerland,  Taiwan,  Thailand,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free Survival (DFS)	Disease-free survival is defined as the interval between randomization and the date of the first occurence of disease recurrence (local, regional or distant), a contralateral invasive breast cancer, a second primary cancer (SPC), or death from any cause. DFS was estimated using the Kaplan Meier method.The percentile data values presented here indicate the percentage (95, 90, 85, 80 and 75 percent) of participants who had disease free survival for the indicated years.	From randomization until the date of the first occurrence of disease recurrence, a contralateral invasive breast cancer, a second primary cancer, or death from any cause (median follow-up of 4.5 years)
Secondary	Overall Survival (OS)	Overall survival is defined as the time from randomization until death due to any cause. Overall survival was calculated in years as (date of death minus the date of randomization +1) divided by 365.25. The percentile data values presented here indicate the percentage (99, 98, 97, 96, 95 and 90 percent) of participants who survived for the indicated years.	From randomization until death due to any cause (median follow-up of 4.5 years)
Secondary	Time to Recurrence	Time to recurrence is defined as the interval between the date of randomization and the date of the first occurrence of a disease recurrence (local, regional or distant). The percentile data values presented here indicate the percentage (95, 90, 85, and 80 percent) of participants who did not have disease recurrence for the indicated years. IDMC=Independent Data Monitoring Committee.	From randomization until the date of the first occurrence of a disease recurrence (median follow-up of 4.5 years)
Secondary	Time to Distant Recurrence	Time to distant recurrence is defined as the interval between the date of randomization and the date of the first occurrence of distant recurrence (including central nervous system recurrence). The percentile data values presented here indicate the percentage (95, 90, 85 and 80 percent) of participants who did not have distant recurrence for the indicated years.	From randomization until the date of the first occurrence of distant recurrence (median follow-up of 4.5 years)
Secondary	Time to Central Nervous System Recurrence	Time to central nervous system recurrence is defined as the time from randomization until the first central nervous system recurrence. Both brain metastasis and meningitis carcinomatosa were considered.The percentile data values presented here indicate that 95 percent of participants did not have central nervous system recurrence for the indicated years.	From randomization until the first central nervous system recurrence (median follow-up of 4.5 years)
Secondary	DFS Ignoring Non-breast Second Primary Malignancies	Disease-free survival is defined as the interval between randomization and the date of the first occurence of disease recurrence (local, regional or distant), a contralateral invasive breast cancer, a second primary cancer, or death from any cause. DFS was estimated using the Kaplan Meier method. The non-breast second primary malignancies were not considered events.The percentile data values presented here indicate the percentage (95, 90, 85, 80 and 75 percent) of participants who did not have DFS ignoring non-breast second primary malignancies for the indicated years. Zero participants were analyzed in the lapatinib arm, as the IDMC discontinued the lapatinib-alone arm due to futility at the time of the first interim analysis (lapatinib participants were then offered trastuzumab).	From randomization until the date of the first occurrence of disease recurrence, a contralateral invasive breast cancer, a second primary cancer, or death from any cause (median follow-up of 4.5 years)