Tykerb Evaluation After Chemotherapy (TEACH): Lapatinib Versus Placebo In Women With Early-Stage Breast Cancer

Neoplasms, Breast Clinical Trial

Official title:

A Randomized, Double-blind, Multicenter, Placebo-controlled Study of Adjuvant Lapatinib (GW572016) in Women With Early-Stage ErbB2 Overexpressing Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00374322
• Other study ID #: EGF105485
• Status: Completed
• Phase: Phase 3
• First received: September 7, 2006
• Last updated: August 14, 2014
• Start date: August 2006
• Est. completion date: July 2013

Study information

• Verified date: July 2014
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study was designed to evaluate and compare the safety and efficacy of an oral dual tyrosine kinase inhibitor, lapatinib, versus placebo in women with early-stage ErbB2-overexpressing breast cancer who have completed their primary neoadjuvant or adjuvant chemotherapy and have no clinical or radiographic evidence of disease.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3166
• Est. completion date: July 2013
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Have histologically or cytologically confirmed ErbB2-overexpressing invasive carcinoma (TX or T1-4) of the breast at the time of the initial diagnosis and have undergone adequate excision of tumor;

• Had tumors that overexpress ErbB2 defined as 3+ by IHC or c-erbB2 gene amplification by FISH (ErbB2 expression/amplification must be documented prior to study entry; however, a tumor tissue sample must be sent to a central laboratory for subsequent re-analysis of ErbB2 status);

• Have Stage I through Stage IIIc disease according to the American Joint Committee on Cancer (6th edition) staging criteria for breast cancer and meet one of the following criteria:

node-positive disease defined as: one positive lymph node by sentinel node biopsy OR at least 1 positive lymph node found among at least 6 axillary nodes examined on axillary node dissection OR status post axillary radiotherapy for sterilization if clinically evaluated as cN1 or cN2 (if sentinel node biopsy is positive, subject may either undergo an axillary node dissection or radiotherapy to the axilla).

node-positive disease evaluated as: ipsilateral axillary lymph nodes cN0-2 by clinical evaluation and axillary lymph nodes pNX, pN0(i+), or pN1-3 by pathological evaluation [patients with pN3 (Stage IIIc disease) must be disease free following completion of neoadjuvant or adjuvant chemotherapy for at least 12 months and must not have been lost to follow up].

OR node-negative disease defined as: negative sentinel node biopsy OR no positive lymph nodes found among at least 6 axillary nodes examined on axillary node dissection OR status post axillary radiotherapy for sterilization if clinically evaluated as cN0.

node-negative disease categorized as: high-risk disease (tumor >2.0 cm if ER and/or progesterone receptor (PgR) positive disease is present or tumor >1.0 cm if ER and PgR negative disease) OR intermediate-risk disease (tumor 1.0-2.0 cm and ER and/or PgR positive disease).

• Women with synchronous bilateral invasive breast cancer or synchronous DCIS of either the contralateral or ipsilateral breast at the time of the initial diagnosis are also eligible;

• Have undergone either mastectomy OR lumpectomy;

• Have received and completed treatment with a neoadjuvant or adjuvant chemotherapy regimen containing either an anthracycline or a taxane; or any cyclophosphamide, methotrexate and 5-fluorouracil (CMF) regimen;

• May continue to receive endocrine therapy while taking study medication, if endocrine therapy was initiated as either adjuvant therapy for treatment of the initial diagnosis of invasive breast cancer or for ovarian function suppression; however, endocrine therapy may not be initiated while taking study medication. Endocrine therapy agents may be switched while participating in this study (e.g., stop tamoxifen and start letrozole);

• May have received prior radiotherapy as treatment for primary tumor; however, is not required for study entry;

• May continue to receive radiotherapy while taking study medication, if radiotherapy was initiated as adjuvant therapy for treatment of the initial diagnosis of invasive breast cancer;

• May continue to receive bisphosphonates only for treatment of documented osteoporosis, but not as treatment or prophylaxis of bone metastases;

• All women eligible for adjuvant treatment with trastuzumab, including those diagnosed and treated within the last six months, must be considered for such treatment prior to being offered participation in this study. Participation in this study will be allowed only if the physician and patient have considered and discussed at length the advantages of trastuzumab, but have mutually decided against initiating trastuzumab therapy.

• Have clinical and radiologic assessments that are negative for local or regional recurrence of disease or metastatic disease at the time of study entry;

• if signs or symptoms suggestive of either recurrence of disease or metastatic disease are present, the appropriate radiological imaging must be performed

• if the following laboratory results are present, the appropriate radiological imaging must be performed:

• for AST/ALT =2×ULN or ALP =2×ULN (not in the bone fraction), an abdominal CT or MRI must be done

• for ALP=2×ULN in the bone fraction, a bone scan must be done; a confirmatory x-ray, CT scan or MRI scan or biopsy is required if the results of the bone scan are inconclusive

• Have a unilateral/bilateral mammogram within 12 months prior to study entry;

• Have an analysis of both ER and PgR on the primary tumor prior to study entry;

• Have a cardiac ejection fraction within institutional range of normal as measured by either echocardiogram or multigated acquisition scans;

• Have an Eastern Cooperative Oncology Group Performance Status of 0 to 1;

• Women with a history of non-breast malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence. Women with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical carcinoma in situ, melanoma in situ, and basal cell or squamous cell carcinoma of the skin;

• Are able to swallow and retain oral medication;

• Have a paraffin-embedded tissue block from an archived tumor tissue from the primary tumor or twenty (20) slides of paraffin-embedded tissue available for biomarker analysis;

• Have adequate organ function defined as: absolute neutrophil count =1.5× 10^9/L; hemoglobin =9 g/dL; platelets =75 × 10^9/L; albumin =2.5 g/dL; serum bilirubin =1.25 ×ULN; aspartate aminotransferase and alanine aminotransferase =3 × ULN and serum creatinine =2.0 mg/dL or calculated creatinine clearance =40 mL/min

• Have signed the informed consent form (ICF);

• Women of child-bearing potential must have a negative serum pregnancy test at screening and agree to complete abstinence from intercourse or consistent and correct use of an acceptable methods of birth control from 2 weeks prior to administration of the first dose of study medication until 28 days after the final dose of study medication:

Exclusion Criteria:

• Have clinical and radiologic evidence of local or regional recurrence of disease or metastatic disease at the time of study entry;

• Had metachronous invasive breast cancer (breast cancers diagnosed at different times);

• Have a prior history of other breast cancer malignancies, including DCIS;

• Are unable to provide archived tumor tissue samples for assay;

• Had prior therapy with an ErbB1 and/or ErbB2 inhibitor; women who experienced a hypersensitivity or allergic reaction to trastuzumab during the first infusion and were unable to complete this infusion are eligible;

• Receive concurrent anti-cancer therapy (chemotherapy, immunotherapy, and biologic therapy) while taking study medication;

• Have unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment;

• Have malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Women with ulcerative colitis are also excluded;

• Have a concurrent disease or condition that would make the woman inappropriate for study participation, or any serious medical disorder that would interfere with the woman's safety;

• Have an active or uncontrolled infection;

• Have dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent;

• Have a known history of uncontrolled or symptomatic angina, arrhythmias, or CHF;

• Are pregnant or breastfeeding;

• Receive concurrent treatment with an investigational agent; women, who are in follow-up in another clinical trial where the primary endpoint has been met and the interval between assessments is =12 months and radiological imaging is not required at these assessments, are eligible;

• Receive concurrent treatment with a selected list of strong inducers and inhibitors of CYP3A4;

• Used an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study medication;

• Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to lapatinib or excipients;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Neoplasms, Breast

Intervention

Drug:
• lapatinib
Lapatinib 1500 mg (6 tablets) daily for 12 months

Other:
• placebo
6 tablets daily for 12 months

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Capital Federal	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires
Argentina	GSK Investigational Site	Córdoba	Córdova
Argentina	GSK Investigational Site	Neuquen	Neuquén
Argentina	GSK Investigational Site	Quilmes
Argentina	GSK Investigational Site	Rosario	Santa Fe
Argentina	GSK Investigational Site	San Miguel de Tucumán
Argentina	GSK Investigational Site	Santa Fe
Australia	GSK Investigational Site	Bedford Park	South Australia
Australia	GSK Investigational Site	Box Hill	Victoria
Australia	GSK Investigational Site	Campbelltown	New South Wales
Australia	GSK Investigational Site	Darlinghurst	New South Wales
Australia	GSK Investigational Site	Douglas	Queensland
Australia	GSK Investigational Site	East Melbourne	Victoria
Australia	GSK Investigational Site	Elizabeth Vale	South Australia
Australia	GSK Investigational Site	Fitzroy	Victoria
Australia	GSK Investigational Site	Footscray	Victoria
Australia	GSK Investigational Site	Heidelberg	Victoria
Australia	GSK Investigational Site	Herston	Queensland
Australia	GSK Investigational Site	Kogarah	New South Wales
Australia	GSK Investigational Site	Liverpool	New South Wales
Australia	GSK Investigational Site	Nedlands	Western Australia
Australia	GSK Investigational Site	North Sydney	New South Wales
Australia	GSK Investigational Site	Parkville	Victoria
Australia	GSK Investigational Site	Perth	Western Australia
Australia	GSK Investigational Site	Redcliffe	Queensland
Australia	GSK Investigational Site	Ringwood East	Victoria
Australia	GSK Investigational Site	South Brisbane	Queensland
Australia	GSK Investigational Site	Wodonga	Victoria
Australia	GSK Investigational Site	Woodville	South Australia
Belgium	GSK Investigational Site	Bruxelles
Brazil	GSK Investigational Site	Belo Horizonte	Minas Gerais
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	Rio de Janeiro
Brazil	GSK Investigational Site	Santo Andre	São Paulo
Brazil	GSK Investigational Site	São Paulo
Canada	GSK Investigational Site	Barrie	Ontario
Canada	GSK Investigational Site	Brampton	Ontario
Canada	GSK Investigational Site	Greenfield Park	Quebec
Canada	GSK Investigational Site	Halifax	Nova Scotia
Canada	GSK Investigational Site	Kingston	Ontario
Canada	GSK Investigational Site	London	Ontario
Canada	GSK Investigational Site	Mississauga	Ontario
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Oshawa	Ontario
Canada	GSK Investigational Site	Ottawa	Ontario
Canada	GSK Investigational Site	Quebec
Canada	GSK Investigational Site	Saskatoon	Saskatchewan
Canada	GSK Investigational Site	St. John's	Newfoundland and Labrador
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Chile	GSK Investigational Site	Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Viña del Mar	Valparaíso
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Guangzhou	Guangdong
China	GSK Investigational Site	Jinan	Shandong
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Tianjin
China	GSK Investigational Site	Wuhan	Hubei
Croatia	GSK Investigational Site	Osijek
Croatia	GSK Investigational Site	Pula
Croatia	GSK Investigational Site	Rijeka
Croatia	GSK Investigational Site	Split
Croatia	GSK Investigational Site	Zagreb
Czech Republic	GSK Investigational Site	Brno
Czech Republic	GSK Investigational Site	Prague 2
Czech Republic	GSK Investigational Site	Praha 8
Denmark	GSK Investigational Site	Aalborg
Denmark	GSK Investigational Site	Copenhagen
Denmark	GSK Investigational Site	Esbjerg
Denmark	GSK Investigational Site	Herlev
Denmark	GSK Investigational Site	Naestved
Denmark	GSK Investigational Site	Odense
Denmark	GSK Investigational Site	Roskilde
Denmark	GSK Investigational Site	Vejle
France	GSK Investigational Site	Angers
France	GSK Investigational Site	Besançon
France	GSK Investigational Site	Bordeaux
France	GSK Investigational Site	Caen Cedex 05
France	GSK Investigational Site	Clermont Ferrand
France	GSK Investigational Site	Colmar Cedex
France	GSK Investigational Site	Dijon Cedex
France	GSK Investigational Site	Lille
France	GSK Investigational Site	Lille cedex
France	GSK Investigational Site	Lyon
France	GSK Investigational Site	Lyon Cedex 08
France	GSK Investigational Site	Marseille Cedex 09
France	GSK Investigational Site	Montbeliard
France	GSK Investigational Site	Montpellier Cedex 5
France	GSK Investigational Site	Nantes cedex
France	GSK Investigational Site	Nice Cedex 2
France	GSK Investigational Site	Paris Cedex 15
France	GSK Investigational Site	Reims
France	GSK Investigational Site	Rennes
France	GSK Investigational Site	Saint Grégoire
France	GSK Investigational Site	Saint-Cloud
France	GSK Investigational Site	Saint-Herblain
France	GSK Investigational Site	Strasbourg
France	GSK Investigational Site	Toulouse Cedex 3
France	GSK Investigational Site	Toulouse Cedex 9
France	GSK Investigational Site	Tourcoing
France	GSK Investigational Site	Vandoeuvre-Les-Nancy
France	GSK Investigational Site	Villejuif
France	GSK Investigational Site	Villejuif Cedex
Germany	GSK Investigational Site	Amberg	Bayern
Germany	GSK Investigational Site	Aschaffenburg	Bayern
Germany	GSK Investigational Site	Bayreuth	Bayern
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Blankenburg	Sachsen-Anhalt
Germany	GSK Investigational Site	Bochum	Nordrhein-Westfalen
Germany	GSK Investigational Site	Bonn	Nordrhein-Westfalen
Germany	GSK Investigational Site	Bremen
Germany	GSK Investigational Site	Bremen
Germany	GSK Investigational Site	Chemnitz	Sachsen
Germany	GSK Investigational Site	Cottbus	Brandenburg
Germany	GSK Investigational Site	Deggendorf	Bayern
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Duesseldorf	Nordrhein-Westfalen
Germany	GSK Investigational Site	Duisburg	Nordrhein-Westfalen
Germany	GSK Investigational Site	Duisburg	Nordrhein-Westfalen
Germany	GSK Investigational Site	Ebersberg	Bayern
Germany	GSK Investigational Site	Eggenfelden	Bayern
Germany	GSK Investigational Site	Eisenach	Thueringen
Germany	GSK Investigational Site	Erlangen	Bayern
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Frankfurt am Main	Hessen
Germany	GSK Investigational Site	Freiburg	Baden-Wuerttemberg
Germany	GSK Investigational Site	Fuerstenwalde	Brandenburg
Germany	GSK Investigational Site	Fuerth	Bayern
Germany	GSK Investigational Site	Goslar	Niedersachsen
Germany	GSK Investigational Site	Guestrow	Mecklenburg-Vorpommern
Germany	GSK Investigational Site	Halle	Sachsen-Anhalt
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hannover	Niedersachsen
Germany	GSK Investigational Site	Heidelberg	Baden-Wuerttemberg
Germany	GSK Investigational Site	Herne	Nordrhein-Westfalen
Germany	GSK Investigational Site	Hilden	Nordrhein-Westfalen
Germany	GSK Investigational Site	Hildesheim	Niedersachsen
Germany	GSK Investigational Site	Homburg/Saar	Saarland
Germany	GSK Investigational Site	Jena	Thueringen
Germany	GSK Investigational Site	Kassel	Hessen
Germany	GSK Investigational Site	Kassel	Hessen
Germany	GSK Investigational Site	Kauschwitz	Sachsen
Germany	GSK Investigational Site	Kempten	Bayern
Germany	GSK Investigational Site	Kiel	Schleswig-Holstein
Germany	GSK Investigational Site	Koblenz	Rheinland-Pfalz
Germany	GSK Investigational Site	Koeln	Nordrhein-Westfalen
Germany	GSK Investigational Site	Koeln	Nordrhein-Westfalen
Germany	GSK Investigational Site	Konstanz	Baden-Wuerttemberg
Germany	GSK Investigational Site	Krumbach	Bayern
Germany	GSK Investigational Site	Luebeck	Schleswig-Holstein
Germany	GSK Investigational Site	Magdeburg	Sachsen-Anhalt
Germany	GSK Investigational Site	Magdeburg	Sachsen-Anhalt
Germany	GSK Investigational Site	Mainz	Rheinland-Pfalz
Germany	GSK Investigational Site	Mannheim	Baden-Wuerttemberg
Germany	GSK Investigational Site	Marktredwitz	Bayern
Germany	GSK Investigational Site	Mayen	Baden-Wuerttemberg
Germany	GSK Investigational Site	Memmingen	Bayern
Germany	GSK Investigational Site	Muelheim	Nordrhein-Westfalen
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Mutlangen	Baden-Wuerttemberg
Germany	GSK Investigational Site	Neunkirchen	Saarland
Germany	GSK Investigational Site	Neustadt	Sachsen
Germany	GSK Investigational Site	Porta Westfalica	Nordrhein-Westfalen
Germany	GSK Investigational Site	Recklinghausen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Rehling	Bayern
Germany	GSK Investigational Site	Rheinfelden	Baden-Wuerttemberg
Germany	GSK Investigational Site	Rosenheim	Bayern
Germany	GSK Investigational Site	Roth	Bayern
Germany	GSK Investigational Site	Saarbruecken	Saarland
Germany	GSK Investigational Site	Salzgitter	Niedersachsen
Germany	GSK Investigational Site	Schwandorf	Bayern
Germany	GSK Investigational Site	Schwetzingen	Baden-Wuerttemberg
Germany	GSK Investigational Site	Singen	Baden-Wuerttemberg
Germany	GSK Investigational Site	Spremberg	Sachsen
Germany	GSK Investigational Site	Stendal	Sachsen-Anhalt
Germany	GSK Investigational Site	Stuttgart	Baden-Wuerttemberg
Germany	GSK Investigational Site	Stuttgart	Baden-Wuerttemberg
Germany	GSK Investigational Site	Troisdorf	Nordrhein-Westfalen
Germany	GSK Investigational Site	Tuebingen	Baden-Wuerttemberg
Germany	GSK Investigational Site	Ulm	Baden-Wuerttemberg
Germany	GSK Investigational Site	Velbert	Nordrhein-Westfalen
Germany	GSK Investigational Site	Weiden	Bayern
Germany	GSK Investigational Site	Wiesbaden	Hessen
Germany	GSK Investigational Site	Witten	Nordrhein-Westfalen
Germany	GSK Investigational Site	Zittau	Sachsen
Germany	GSK Investigational Site	Zwickau	Sachsen
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Chania
Greece	GSK Investigational Site	Heraklion, Crete
Hong Kong	GSK Investigational Site	Hong Kong
Hong Kong	GSK Investigational Site	Shatin
Hong Kong	GSK Investigational Site	Wanchai
Hungary	GSK Investigational Site	Budapest
Hungary	GSK Investigational Site	Budapest
Hungary	GSK Investigational Site	Gyor
Hungary	GSK Investigational Site	Kaposvár
Hungary	GSK Investigational Site	Kistarcsa
Hungary	GSK Investigational Site	Pécs
Hungary	GSK Investigational Site	Szeged
India	GSK Investigational Site	Chennai
India	GSK Investigational Site	Hyderabad
India	GSK Investigational Site	Jaipur
India	GSK Investigational Site	Mumbai
India	GSK Investigational Site	New Delhi
India	GSK Investigational Site	Pune
Israel	GSK Investigational Site	Ashkelon
Israel	GSK Investigational Site	Haifa
Israel	GSK Investigational Site	Jerusalem
Israel	GSK Investigational Site	Kfar Saba
Israel	GSK Investigational Site	Ramat Gan
Israel	GSK Investigational Site	Rehovot
Israel	GSK Investigational Site	Tel Aviv
Italy	GSK Investigational Site	Avellino	Campania
Italy	GSK Investigational Site	Genova	Liguria
Italy	GSK Investigational Site	Negrar (Verona)	Veneto
Italy	GSK Investigational Site	Perugia	Umbria
Italy	GSK Investigational Site	Piacenza	Emilia-Romagna
Italy	GSK Investigational Site	Sassari	Sardegna
Korea, Republic of	GSK Investigational Site	Goyang-si, Gyeonggi-do
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	songpa-gu, Seoul
Latvia	GSK Investigational Site	Liepaja
Latvia	GSK Investigational Site	Riga
Latvia	GSK Investigational Site	Riga
Lithuania	GSK Investigational Site	Kaunas
Lithuania	GSK Investigational Site	Klaipeda
Lithuania	GSK Investigational Site	Vilnius
Mexico	GSK Investigational Site	Chihuahua
Mexico	GSK Investigational Site	DF.
Mexico	GSK Investigational Site	Mérida	Yucatán
Mexico	GSK Investigational Site	Mexico City
Mexico	GSK Investigational Site	México D.F.
New Zealand	GSK Investigational Site	Auckland
New Zealand	GSK Investigational Site	Christchurch
New Zealand	GSK Investigational Site	Hamilton
Peru	GSK Investigational Site	Lima
Peru	GSK Investigational Site	Lima
Peru	GSK Investigational Site	Lima
Philippines	GSK Investigational Site	Baguio City, Benguet
Philippines	GSK Investigational Site	Cebu
Philippines	GSK Investigational Site	Pasig City
Philippines	GSK Investigational Site	Quezon City
Poland	GSK Investigational Site	Bydgoszcz
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Olsztyn
Poland	GSK Investigational Site	Olsztyn
Poland	GSK Investigational Site	Torun
Poland	GSK Investigational Site	Warszawa
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Ryazan
Russian Federation	GSK Investigational Site	St. Petersburg
Russian Federation	GSK Investigational Site	St. Petersburg
Russian Federation	GSK Investigational Site	Yaroslavl
Slovakia	GSK Investigational Site	Banska Bystrica
Slovakia	GSK Investigational Site	Bardejov
Slovakia	GSK Investigational Site	Bratislava
Slovakia	GSK Investigational Site	Nitra
South Africa	GSK Investigational Site	Athlone Park, Amanzimtoti
South Africa	GSK Investigational Site	Groenkloof
South Africa	GSK Investigational Site	Kraaifontein
South Africa	GSK Investigational Site	Overport
South Africa	GSK Investigational Site	Parktown
South Africa	GSK Investigational Site	Port Elizabeth
South Africa	GSK Investigational Site	Sandton
South Africa	GSK Investigational Site	Saxonwold, Johannesburg
South Africa	GSK Investigational Site	Tygerberg	Western Province
Spain	GSK Investigational Site	Alcorcon
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Cáceres
Spain	GSK Investigational Site	Girona
Spain	GSK Investigational Site	Jaén
Spain	GSK Investigational Site	Lerida
Spain	GSK Investigational Site	Llobregat
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Mataró
Spain	GSK Investigational Site	Orense
Spain	GSK Investigational Site	Palma de Mallorca
Spain	GSK Investigational Site	Palma de Mallorca
Spain	GSK Investigational Site	Santa Cruz de Tenerife
Spain	GSK Investigational Site	Santander
Spain	GSK Investigational Site	Santiago de Compostela
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Zaragoza
Ukraine	GSK Investigational Site	Dnepropetrovsk
Ukraine	GSK Investigational Site	Kyiv
Ukraine	GSK Investigational Site	Lvov
Ukraine	GSK Investigational Site	Uzhgorod
United Kingdom	GSK Investigational Site	Bournemouth
United Kingdom	GSK Investigational Site	Chelmsford	Essex
United Kingdom	GSK Investigational Site	Edgbaston, Birmingham
United Kingdom	GSK Investigational Site	Glasgow
United Kingdom	GSK Investigational Site	Lindley
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	Maidstone
United Kingdom	GSK Investigational Site	Manchester
United Kingdom	GSK Investigational Site	Manchester	Lancashire
United Kingdom	GSK Investigational Site	Newcastle upon Tyne
United Kingdom	GSK Investigational Site	Nottingham
United Kingdom	GSK Investigational Site	Sheffield
United Kingdom	GSK Investigational Site	Shrewsbury
United Kingdom	GSK Investigational Site	Sutton	Surrey
United States	GSK Investigational Site	Albany	New York
United States	GSK Investigational Site	Ames	Iowa
United States	GSK Investigational Site	Anaheim	California
United States	GSK Investigational Site	Augusta	Georgia
United States	GSK Investigational Site	Austin	Texas
United States	GSK Investigational Site	Austin	Texas
United States	GSK Investigational Site	Bakersfield	California
United States	GSK Investigational Site	Bedford	Texas
United States	GSK Investigational Site	Bethesda	Maryland
United States	GSK Investigational Site	Boca Raton	Florida
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Boynton Beach	Florida
United States	GSK Investigational Site	Charleston	North Carolina
United States	GSK Investigational Site	Charleston	South Carolina
United States	GSK Investigational Site	Chattanooga	Tennessee
United States	GSK Investigational Site	Cherry Hill	New Jersey
United States	GSK Investigational Site	Chesapeake	Virginia
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Cleveland	Ohio
United States	GSK Investigational Site	Cleveland	Ohio
United States	GSK Investigational Site	Columbia	Missouri
United States	GSK Investigational Site	Columbus	Ohio
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Danvers	Massachusetts
United States	GSK Investigational Site	Denver	Colorado
United States	GSK Investigational Site	Drexel Hill	Pennsylvania
United States	GSK Investigational Site	Duluth	Minnesota
United States	GSK Investigational Site	Duncanville	Texas
United States	GSK Investigational Site	East Setauket	New York
United States	GSK Investigational Site	Edina	Minnesota
United States	GSK Investigational Site	El Paso	Texas
United States	GSK Investigational Site	Fairfax	Virginia
United States	GSK Investigational Site	Fairfield	Connecticut
United States	GSK Investigational Site	Fayetteville	Arkansas
United States	GSK Investigational Site	Fort Worth	Texas
United States	GSK Investigational Site	Gainesville	Florida
United States	GSK Investigational Site	Gastonia	North Carolina
United States	GSK Investigational Site	Germantown	Tennessee
United States	GSK Investigational Site	Gilroy	California
United States	GSK Investigational Site	Greensboro	North Carolina
United States	GSK Investigational Site	Hickory	North Carolina
United States	GSK Investigational Site	Hooksett	New Hampshire
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Indianapolis	Indiana
United States	GSK Investigational Site	Joliet	Illinois
United States	GSK Investigational Site	Jonesboro	Arkansas
United States	GSK Investigational Site	Kalamazoo	Michigan
United States	GSK Investigational Site	Kansas City	Missouri
United States	GSK Investigational Site	Kirkland	Washington
United States	GSK Investigational Site	La Jolla	California
United States	GSK Investigational Site	La Verne	California
United States	GSK Investigational Site	Little Rock	Arkansas
United States	GSK Investigational Site	Louisville	Kentucky
United States	GSK Investigational Site	Marietta	Georgia
United States	GSK Investigational Site	Marrero	Louisiana
United States	GSK Investigational Site	Memphis	Tennessee
United States	GSK Investigational Site	Middletown	Ohio
United States	GSK Investigational Site	Minneapolis	Minnesota
United States	GSK Investigational Site	Morristown	New Jersey
United States	GSK Investigational Site	Mount Kisco	New York
United States	GSK Investigational Site	New Port Richey	Florida
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Newton	Massachusetts
United States	GSK Investigational Site	Norwalk	Connecticut
United States	GSK Investigational Site	Ocala	Florida
United States	GSK Investigational Site	Ogden	Utah
United States	GSK Investigational Site	Orlando	Florida
United States	GSK Investigational Site	Palm Springs	California
United States	GSK Investigational Site	Paramus	New Jersey
United States	GSK Investigational Site	Park Ridge	Illinois
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Plantation	Florida
United States	GSK Investigational Site	Port St. Lucie	Florida
United States	GSK Investigational Site	Rancho Mirage	California
United States	GSK Investigational Site	Richland	Virginia
United States	GSK Investigational Site	Robbinsdale	Minnesota
United States	GSK Investigational Site	Rochester	New York
United States	GSK Investigational Site	Round Rock	Texas
United States	GSK Investigational Site	Saint Louis	Missouri
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	Scarborough	Maine
United States	GSK Investigational Site	Seattle	Washington
United States	GSK Investigational Site	Sedona	Arizona
United States	GSK Investigational Site	Sioux City	Iowa
United States	GSK Investigational Site	Sparta	New Jersey
United States	GSK Investigational Site	St. Joseph	Missouri
United States	GSK Investigational Site	St. Louis	Missouri
United States	GSK Investigational Site	Torrington	Connecticut
United States	GSK Investigational Site	Tucson	Arizona
United States	GSK Investigational Site	Tuscaloosa	Alabama
United States	GSK Investigational Site	Tyler	Texas
United States	GSK Investigational Site	Vancouver	Washington
United States	GSK Investigational Site	Waco	Texas
United States	GSK Investigational Site	Washington	District of Columbia
United States	GSK Investigational Site	Washington	District of Columbia
United States	GSK Investigational Site	Wichita	Kansas
United States	GSK Investigational Site	Yakima	Washington

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  Chile,  China,  Croatia,  Czech Republic,  Denmark,  France,  Germany,  Greece,  Hong Kong,  Hungary,  India,  Israel,  Italy,  Korea, Republic of,  Latvia,  Lithuania,  Mexico,  New Zealand,  Peru,  Philippines,  Poland,  Russian Federation,  Slovakia,  South Africa,  Spain,  Ukraine,  United Kingdom, 

References & Publications (1)

Goss PE, Smith IE, O'Shaughnessy J, Ejlertsen B, Kaufmann M, Boyle F, Buzdar AU, Fumoleau P, Gradishar W, Martin M, Moy B, Piccart-Gebhart M, Pritchard KI, Lindquist D, Chavarri-Guerra Y, Aktan G, Rappold E, Williams LS, Finkelstein DM; TEACH investigators. Adjuvant lapatinib for women with early-stage HER2-positive breast cancer: a randomised, controlled, phase 3 trial. Lancet Oncol. 2013 Jan;14(1):88-96. doi: 10.1016/S1470-2045(12)70508-9. Epub 2012 Dec 10. Erratum in: Lancet Oncol. 2013 Feb;14(2):e47. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants (Par.) With Any Recurrence of the Initial Disease, Second Primary Cancer, Contralateral Breast Cancer, or Death (Disease-free Survival [DFS])	DFS=interval between the date of randomization and the date of the first occurrence of an objective disease recurrence, a second primary cancer, or death from any cause. The date of the event is the earliest date of the occurrence of any of the following: local recurrence (LR) following mastectomy; LR in ipsilateral breast following lumpectomy; regional recurrence; distant recurrence; contralateral breast cancer, including ductal carcinoma in situ; other second primary cancer (excluding squamous or basal cell carcinoma of the skin, melanoma in situ, carcinoma in situ of the cervix, or lobular carcinoma in situ of the breast); death from any cause without a prior event. Par. who started additional anti-cancer adjuvant therapy prior to the recurrence of their disease were to be censored. Par. who did not withdraw from the study and did not experience a specified event or death were to be censored (follow-up ongoing) at the last visit date available at which progression was assessed.	From randomization until date of the first occurrence of an objective disease recurrence, a second primary cancer, or death from any cause (assessed up to 6 years; 1 year of treatment, 5 years of follow-up [median of 5.3 years for final analysis])	No
Secondary	Number of Participants Who Died (Overall Survival)	Overall Survival (OS) is defined as the time from randomization until death from any cause. Data are presented as the number of participants who died. For participants who did not die, time to death was censored at the last date the participant was known to be alive.	From the date of randomization until death from any cause (assessed up to 6 years; 1 year of treatment and 5 years of follow-up [median of 5.3 years for final analysis])	No
Secondary	Percentage of Participants With the Indicated Period of Recurrence-free Survival (Time to First Recurrence)	Recurrence is defined as experiencing a recurrence of initial disease or contralateral breast cancer after randomization. Time to first recurrence is defined as the interval between the date of randomization and the date of the first occurrence of an objective disease recurrence or contralateral breast cancer. Time to first recurrence included the first occurrence at one of the following sites as an event: local recurrence following mastectomy; local recurrence in ipsilateral breast following lumpectomy; regional recurrence; distant recurrence; contralateral breast cancer, including ductal carcinoma in situ (DCIS).	From the date of randomization until the date of the first occurrence of an objective disease recurrence or contralateral breast cancer (assessed up to 6 years; 1 year of treatment and 5.3 years of follow-up [median of 5 years for final analysis])	No
Secondary	Percentage of Participants With the Indicated Period of Distant Recurrence-free Survival (Time to Distant Recurrence)	Distant recurrence (metastatic disease) is defined as a tumor in any area of the body not including those defined as local or regional recurrence. Sites of distant recurrence include: skin, subcutaneous tissue, and lymph nodes (excluding those described for local and regional recurrence); bone marrow; skeletal; lungs and pleural; ascites and pleural effusions; liver and other viscera; and central nervous system (CNS). Time to distant recurrence is defined as the interval between the date of randomization and the date of the first occurrence of a distant recurrence.	From the date of randomization until the date of the first occurrence of a distant recurrence (assessed up to 6 years; 1 year of treatment and 5 years of follow-up [median of 5.3 years for final analysis])	No
Secondary	Time to Central Nervous System (CNS) Recurrence	Time to CNS recurrence is defined as the interval between the date of randomization and the date of the occurrence of a CNS recurrence if noted as part of the participant's first recurrence. Time to CNS recurrence was not calculated; data are presented as the number of participants with CNS recurrence in the subsequent outcome measure table.	From the date of randomization until the date of the first occurrence of a CNS recurrence (assessed up to 6 years [1 year of treatment and 5 years of follow-up; median of 5.3 years for final analysis])	No
Secondary	Number of Participants With CNS Recurrence	The number of participants experiencing a CNS recurrence was summarized.	From the date of randomization until the date of the first occurrence of a CNS recurrence (assessed up to 6 years [1 year of treatment and 5 years of follow-up; median of 5.3 years for final analysis])	No
Secondary	Modified Disease-free Survival (MDFS)	Modified disease recurrence=interval between the date of randomization and the date of the first occurrence of an objective disease recurrence, contralateral breast cancer, or death from any cause. The date of the event=the earliest date of the occurrence of any of the following events: local recurrence following mastectomy; local recurrence in ipsilateral breast following lumpectomy; regional recurrence; distant recurrence; contralateral breast cancer, including DCIS; death from any cause without a prior event. MDFS was not calculated; data are presented as the number of participants with any recurrence of the initial disease, contralateral breast cancer, or death (disease-free survival) in the subsequent outcome measure table.	From the date of randomization until the date of the first occurrence of an objective disease recurrence, contralateral breast cancer, or death from any cause (assessed up to 6 years)	No
Secondary	Number of Participants With Any Recurrence of the Initial Disease, Contralateral Breast Cancer, or Death (Disease-free Survival [DFS])	DFS=interval between the date of randomization and the date of the first occurrence of an objective disease recurrence, a second primary cancer, or death from any cause. The date of the event is the earliest date of the occurrence of any of the following: local recurrence (LR) following mastectomy; LR in ipsilateral breast following lumpectomy; regional recurrence; distant recurrence and contralateral breast cancer, including ductal carcinoma in situ; or death from any cause without a prior event. Participants who started additional anti-cancer adjuvant therapy prior to the recurrence of their disease were to be censored. Participants who did not withdraw from the study and did not experience a specified event or death were to be censored (follow-up ongoing) at the last visit date available at which progression was assessed.	From the date of randomization until the date of the first occurrence of an objective disease recurrence, contralateral breast cancer, or death from any cause (assessed up to 6 years)	No
Secondary	Change From Baseline in Short Form-36 Version 2 (SF-36 v2) Scores for the Physical Component Summary (PCS)	The SF-36 v2 is a self-administered, health-related quality of life (QoL) metric. It is a 36-item questionnaire designed to measure 8 domains of functional health status and well-being: physical functioning, role-physical, bodily pain, general health perceptions, vitality, social functioning, role-emotional, and mental health. Each domain is scored from 0 (poorer health) to 100 (better health).The PCS score is a summary score representing overall physical health, which is derived from the 8 domain scores. As with each domain score, the PCS score ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Missing post-Baseline data were imputed using the last observation carried forward (LOCF) method. The scores were analyzed using an analysis of covariance (ANCOVA) model, adjusting for Baseline sub-scale score, treatment, and country. Positive changes from Baseline indicate improvement.	Baseline, Month 6, Month 12, and every 6 months after discontinuation of study treatment for 24 months (up to a maximum of 3 study years)	No
Secondary	Change From Baseline in SF-36 v2 Scores for the Mental Component Summary (MCS)	The SF-36 v2 is a self-administered, health-related quality of life (QoL) metric. It is a 36-item questionnaire designed to measure 8 domains of functional health status and well-being: physical functioning, role-physical, bodily pain, general health perceptions, vitality, social functioning, role-emotional, and mental health. Each domain is scored from 0 (poorer health) to 100 (better health).The MCS score is a summary score representing overall mental health, which is derived from the 8 domain scores. As with each domain score, the MCS score ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Missing post-Baseline data were imputed using the LOCF method. The scores were analyzed using an ANCOVA model adjusting for Baseline sub-scale score, treatment, and country. Positive changes from Baseline indicate improvement.	Baseline, Month 6, Month 12, and every 6 months after discontinuation of study treatment for 24 months (up to a maximum of 3 study years)	No
Secondary	Change From Baseline in the SF-36 v2 Domain Scores for Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH)	The SF-36 v2 is a self-administered, health-related quality of life (QoL) metric. It is a 36-item questionnaire designed to measure 8 domains of functional health status and well-being: physical functioning (PF), role-physical (RP), bodily pain (BP), general health (GH) perceptions, vitality (VT), social functioning (SF), role-emotional (RE), and mental health (MH). Each domain is scored from 0 (poorer health) to 100 (better health); higher scores represent better health. Change from Baseline was calculated as the post-Baseline score minus the Baseline score. Missing post-Baseline data were imputed using the LOCF method. The scores were analyzed using an ANCOVA model, adjusting for Baseline sub-scale score, treatment, and country. Positive changes from Baseline indicate improvement.	Baseline, Month 6, Month 12, and every 6 months after discontinuation of study treatment for 24 months (up to a maximum of 3 study years)	No
Secondary	Number of Participants With Hematology Values Outside the Reference Range for the Indicated Parameters	The hematology parameters assessed were: basophils (Bs) in giga (10^9) per liter (GI/L) and in percentage (%), eosinophils (Eo) in GI/L and %, hematocrit, hemoglobin, lymphocytes (Lmph) in GI/L and %, monocytes (Mono) in GI/L and %, platelet count, Red Blood Cell (RBC) count, total neutrophil count (TNC) in GI/L and %, and White Blood Cell (WBC) count. The Baseline (BL) value is the last available pre-treatment result recorded. "Any post-Baseline value" was based on results recorded at any scheduled or unscheduled post-Baseline visits. The prevalence of values lying outside the reference (ref.) range (high or low) is presented for BL and "any post-Baseline" (APBL) visit. Two participants were randomized to placebo but received lapatinib; therefore, they are included in the lapatinib treatment arm. Data for the primary analysis (conducted in 2011) are reported.	At Baseline and every 3 months thereafter up to Month 12/Early Withdrawal Visit	No
Secondary	Number of Participants With Clinical Chemistry Values Outside the Reference Range for the Indicated Parameters	The clinical chemistry parameters assessed were: alanine amino transferase (ALT), albumin, alkaline phosphatase (ALP), aspartate amino transferase (AST), bicarbonate, blood urea nitrogen (BUN), bone alkaline phosphatase (Bone ALP), calcium, chloride, creatinine, creatinine clearance (Cr. Clearance), creatinine clearance estimated (Cr. Clrnc. est.), glucose, potassium, sodium, total bilirubin (Total Bln), total protein, urea, and uric acid. The Baseline (BL) value is the last available pre-treatment result recorded. "Any post-Baseline" value was based on results recorded at scheduled or unscheduled post-Baseline visits. The prevalence of values lying outside the reference (ref.) range (high or low) was presented for BL and "any post-Baseline" (APBL) visit. Two participants were randomized to placebo but received lapatinib; therefore, they are included in the lapatinib treatment arm.	At Baseline and every 6 weeks thereafter up to Month 12/Early Withdrawal Visit	No
Secondary	Number of Participants With Non-laboratory Toxicities of the Indicated Toxicity Grades	Non-laboratory toxicities are defined as adverse events (AEs). The number of partcipants with any treatment-emergent AE of the indicated toxicity grade are summarized. Toxicity grading was according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 as follows: Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life threatening; Grade 5=death. The events that were not given a toxicity grade are categorized as "Not Applicable."	From the first dose of study treatment up to 12 months	No
Secondary	Number of Participants Experiencing Primary or Secondary Cardiac Events	A cardiac event is classified as a primary cardiac endpoint (PCE) or a secondary cardiac endpoint (SCE). PCE is defined as: cardiac death (cardiac death due to heart failure, myocardial infarction, or arrhythmia;or probable cardiac death defined as sudden, unexpected death within 24 hours of a definite or probable cardiac event); severe symptomatic congestive heart failure (CHF) (as per New York Heart Association [NYHA] Class III or IV and an absolute decrease in left ventricular ejection fraction [LVEF] of more than 10 percentage points from Baseline and to a left ventricular ejection fraction [LVEF] value below 50%). SCE is defined as asymptomatic or mildly symptomatic cardiac events (NYHA Class I or II) and a significant decrease in LVEF, defined as an absolute decrease in LVEF of more than 10 percentage points from Baseline and to an LVEF value below 50%.	From the date of randomization up to 12 months	No
Secondary	Number of Participants With the Indicated Electrocardiogram (ECG) Findings	12-lead ECG measurements were taken at Screening and at study conclusion/withdrawal. The number of participants with normal, abnormal clinically significant (CS), and abnormal not clinically significant (NCS) ECG findings, as classified by the investigator, were summarized. Participants with missing values were categorized as missing. Data for the primary analysis (conducted in 2011) are reported.	Screening and Month 12/Early Withdrawal Visit	No