Paclitaxel With / Without GW572016 (Lapatinib) As First Line Therapy For Women With Advanced Or Metastatic Breast Cancer

Neoplasms, Breast Clinical Trial

Official title:

A Randomized, Multicenter, Double-Blind, Placebo-Controlled, 2-Arm, Phase III Study of Oral GW572016 in Combination With Paclitaxel in Subjects Previously Untreated or Advanced or Metastatic Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00075270
• Other study ID #: EGF30001
• Status: Completed
• Phase: Phase 3
• First received: January 7, 2004
• Last updated: April 16, 2015
• Start date: January 2004
• Est. completion date: March 2012

Study information

• Verified date: February 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

The purpose of this study is to determine the efficacy and safety of an oral dual tyrosine kinase inhibitor (GW572016) in combination with paclitaxel compared to paclitaxel alone in first line advanced or metastatic breast cancer.

Other known NCT identifiers

• NCT00085046

Recruitment information / eligibility

• Status: Completed
• Enrollment: 580
• Est. completion date: March 2012
• Est. primary completion date: October 2006
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Signed Informed Consent

• Able to swallow an oral medication

• Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram

• Adequate kidney and liver function

• Adequate bone marrow function

• Tumor tissue available for testing

• Prior adjuvant or neoadjuvant therapy is permitted with an anthracycline or anthracenedione-containing regimen however, subjects must have had cumulative doses of less than 360 mg/m2 of doxorubicin, 720 mg/m2 of epirubicin, or 72 mg/m2 of mitoxantrone

• No Her2/neu overexpression in tumor tissue tested or status unknown if tissue has never been tested

Exclusion criteria:

• Prior treatment regimens for advanced or metastatic breast cancer.

• Pregnant or lactating

• Conditions that would effect the absorption of an oral drug

• Active infection

• Brain metastases

• Treatment with EGFR (Endothelial Growth Factor Receptor) inhibitor.

• Known hypersensitivity to Taxol or excipients of Taxol

• Peripheral neuropathy of Grade 2 or greater is not permitted

• Severe Cardiovascular disease or cardiac disease requiring a device.

• Serious medical or psychiatric disorder that would interfere with the patient's safety or informed consent.

Study Design

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Neoplasms, Breast

Intervention

Drug:
• Paclitaxel
Active Comparator
• GW572016 (Lapatinib)
Oral GW572016 Lapatinib

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Capital Federal	Buenos Aires
Argentina	GSK Investigational Site	Capital Federal	Buenos Aires
Australia	GSK Investigational Site	Fitzroy	Victoria
Australia	GSK Investigational Site	Malvern	Victoria
Australia	GSK Investigational Site	Nedlands	Western Australia
Australia	GSK Investigational Site	Wodonga	Victoria
Austria	GSK Investigational Site	Vienna
Belgium	GSK Investigational Site	Brugge
Belgium	GSK Investigational Site	Brussel
Belgium	GSK Investigational Site	Brussels
Belgium	GSK Investigational Site	Kortrijk
Belgium	GSK Investigational Site	Leuven
Belgium	GSK Investigational Site	Roeselare
Brazil	GSK Investigational Site	Rio de Janeiro
Brazil	GSK Investigational Site	Salvador	Bahía
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Saint John's	Newfoundland and Labrador
Canada	GSK Investigational Site	Sherbrooke	Quebec
Canada	GSK Investigational Site	Sudbury	Ontario
Canada	GSK Investigational Site	Thunder Bay	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
Czech Republic	GSK Investigational Site	Brno
Czech Republic	GSK Investigational Site	Hradec Kralove
Czech Republic	GSK Investigational Site	Olomouc
Germany	GSK Investigational Site	Aalen	Baden-Wuerttemberg
Germany	GSK Investigational Site	Augsburg	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	Coburg	Bayern
Germany	GSK Investigational Site	Fuerstenwalde	Brandenburg
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	Herne	Nordrhein-Westfalen
Germany	GSK Investigational Site	Ibbenbueren	Nordrhein-Westfalen
Germany	GSK Investigational Site	Jena	Thueringen
Germany	GSK Investigational Site	Kiel	Schleswig-Holstein
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Muenster	Nordrhein-Westfalen
Germany	GSK Investigational Site	Stade	Niedersachsen
Germany	GSK Investigational Site	Stuttgart	Baden-Wuerttemberg
Germany	GSK Investigational Site	Ulm	Baden-Wuerttemberg
Hungary	GSK Investigational Site	Budapest
Hungary	GSK Investigational Site	Nyíregyháza
Hungary	GSK Investigational Site	Szombathely
Hungary	GSK Investigational Site	Zalaegerszeg-Pózva
Italy	GSK Investigational Site	Benevento	Campania
Italy	GSK Investigational Site	Bergamo	Lombardia
Italy	GSK Investigational Site	Candiolo (TO)	Piemonte
Italy	GSK Investigational Site	Forlì	Emilia-Romagna
Italy	GSK Investigational Site	Napoli	Campania
Italy	GSK Investigational Site	Parma	Emilia-Romagna
Italy	GSK Investigational Site	Pavia	Lombardia
Italy	GSK Investigational Site	Perugia	Umbria
Italy	GSK Investigational Site	Pietra Ligure (SV)	Liguria
Italy	GSK Investigational Site	Prato (PO)	Toscana
Italy	GSK Investigational Site	Ravenna	Emilia-Romagna
Italy	GSK Investigational Site	Rimini	Emilia-Romagna
Italy	GSK Investigational Site	Roma	Lazio
Italy	GSK Investigational Site	Roma	Lazio
Italy	GSK Investigational Site	Sassari	Sardegna
Italy	GSK Investigational Site	Torino	Piemonte
Korea, Republic of	GSK Investigational Site	Gyeonggi-do
Korea, Republic of	GSK Investigational Site	Seoul
Latvia	GSK Investigational Site	Daugavpils
Latvia	GSK Investigational Site	Liepaja
Latvia	GSK Investigational Site	Riga
Latvia	GSK Investigational Site	Riga
Mexico	GSK Investigational Site	Acapulco	Guerrero
Mexico	GSK Investigational Site	Colima
Mexico	GSK Investigational Site	Durango
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Netherlands	GSK Investigational Site	Amersfoort
Netherlands	GSK Investigational Site	Leiden
Netherlands	GSK Investigational Site	Nieuwegein
Netherlands	GSK Investigational Site	Utrecht
Netherlands	GSK Investigational Site	Utrecht
New Zealand	GSK Investigational Site	Auckland
New Zealand	GSK Investigational Site	Christchurch
Pakistan	GSK Investigational Site	Lahore
Pakistan	GSK Investigational Site	Lahore
Peru	GSK Investigational Site	Callao
Peru	GSK Investigational Site	Lima
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Olsztyn
Poland	GSK Investigational Site	Olsztyn
Poland	GSK Investigational Site	Poznan
Poland	GSK Investigational Site	Warszawa
Poland	GSK Investigational Site	Wroclaw
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow Region
Russian Federation	GSK Investigational Site	St. Petersburg
Russian Federation	GSK Investigational Site	St. Petersburg
Slovakia	GSK Investigational Site	Banska Bystrica
Slovakia	GSK Investigational Site	Bratislava
Slovakia	GSK Investigational Site	Kosice
Slovakia	GSK Investigational Site	Poprad
South Africa	GSK Investigational Site	Capital Park
South Africa	GSK Investigational Site	Overport
South Africa	GSK Investigational Site	Parktown	Gauteng
South Africa	GSK Investigational Site	Parow
South Africa	GSK Investigational Site	Port Elizabeth
Spain	GSK Investigational Site	Alcorcón/Madrid
Spain	GSK Investigational Site	Baracaldo/Vizcaya
Spain	GSK Investigational Site	Caceres
Spain	GSK Investigational Site	Cuidad Real
Spain	GSK Investigational Site	Jaen
Spain	GSK Investigational Site	La Laguna (Santa Cruz de Tenerife)
Spain	GSK Investigational Site	Las Palmas De Gran Canaria
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Móstoles/Madrid
Spain	GSK Investigational Site	Palma de Mallorca
Spain	GSK Investigational Site	Pontevedra
Spain	GSK Investigational Site	San Sebastián
Spain	GSK Investigational Site	Santa Cruz de Tenerife
Spain	GSK Investigational Site	Zaragoza
Spain	GSK Investigational Site	Zaragoza
Turkey	GSK Investigational Site	Istanbul
Turkey	GSK Investigational Site	Istanbul
United States	GSK Investigational Site	Amarillo	Texas
United States	GSK Investigational Site	Atlanta	Georgia
United States	GSK Investigational Site	Baltimore	Maryland
United States	GSK Investigational Site	Boca Raton	Florida
United States	GSK Investigational Site	Burlington	Vermont
United States	GSK Investigational Site	Canton	Ohio
United States	GSK Investigational Site	Charlotte	North Carolina
United States	GSK Investigational Site	Columbia	South Carolina
United States	GSK Investigational Site	Denver	Colorado
United States	GSK Investigational Site	Duluth	Minnesota
United States	GSK Investigational Site	Fargo	North Dakota
United States	GSK Investigational Site	Fort Worth	Texas
United States	GSK Investigational Site	Fountain Valley	California
United States	GSK Investigational Site	Glen Burnie	Maryland
United States	GSK Investigational Site	Greenville	North Carolina
United States	GSK Investigational Site	Hot Springs	Arkansas
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Indianapolis	Indiana
United States	GSK Investigational Site	Jonesboro	Arkansas
United States	GSK Investigational Site	Kansas City	Kansas
United States	GSK Investigational Site	Knoxville	Tennessee
United States	GSK Investigational Site	Knoxville	Tennessee
United States	GSK Investigational Site	La Jolla	California
United States	GSK Investigational Site	Marietta	Georgia
United States	GSK Investigational Site	Metairie	Louisiana
United States	GSK Investigational Site	Milwaukee	Wisconsin
United States	GSK Investigational Site	Norfolk	Virginia
United States	GSK Investigational Site	Nyack	New York
United States	GSK Investigational Site	Orlando	Florida
United States	GSK Investigational Site	Port St. Lucie	Florida
United States	GSK Investigational Site	Portland	Oregon
United States	GSK Investigational Site	Rancho Mirage	California
United States	GSK Investigational Site	Robbinsdale	Minnesota
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	Santa Fe	New Mexico
United States	GSK Investigational Site	Savannah	Georgia
United States	GSK Investigational Site	Savannah	Georgia
United States	GSK Investigational Site	Springfield	Massachusetts
United States	GSK Investigational Site	St. Louis	Missouri
United States	GSK Investigational Site	Syracuse	New York
United States	GSK Investigational Site	Tacoma	Washington
United States	GSK Investigational Site	Tucson	Arizona
United States	GSK Investigational Site	Vallejo	California
United States	GSK Investigational Site	Voorhees	New Jersey
United States	GSK Investigational Site	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  Czech Republic,  Germany,  Hungary,  Italy,  Korea, Republic of,  Latvia,  Mexico,  Netherlands,  New Zealand,  Pakistan,  Peru,  Poland,  Russian Federation,  Slovakia,  South Africa,  Spain,  Turkey, 

References & Publications (2)

Finn RS, Press MF, Dering J, Arbushites M, Koehler M, Oliva C, Williams LS, Di Leo A. Estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2), and epidermal growth factor receptor expression and benefit from lapatinib in a randomized trial of paclitaxel with lapatinib or placebo as first-line treatment in HER2-negative or unknown metastatic breast cancer. J Clin Oncol. 2009 Aug 20;27(24):3908-15. doi: 10.1200/JCO.2008.18.1925. Epub 2009 Jul 20. — View Citation

Leonardo Tenori, Catherine Oakman, Wederson M. Claudino, Patrizia Bernini, Silvia Cappadona , Stefano Nepi, Laura Biganzoli , Claudio Luchinat, Ivano Bertini, Angelo Di Leo . Correlation of 'on-treatment' serum metabolomic profiles with outcomes in patients with HER2-positive metastatic breast cancer. Molecular Oncologyhas. 2012;6(4):437-44. .

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Progression as Evaluated by the Investigator	Time to progression (TTP) is defined as the interval between the date of randomization and the earliest date of progression of disease (PD) or death due to breast cancer. The investigator assessed PD based on radiological PD (imaging data) and clinical symptomatic progress (Response Evaluation Criteria in Solid Tumors [RECIST] Criteria: target lesion (TL), at least a 20% increase in the sum of largest diameter (LD) of TLs or the appearance of one or more new lesions; non-TL (NTL), the appearance of one or more new lesions and/or unequivocal progression of existing NTLs). TTP was assessed in participants who died due to breast cancer or progressed, as assessed by the investigator, as well as in those who were censored and completed follow-up and those who were censored but are still being followed. For censored participants (those without a documented date of disease progression/death due to breast cancer), the date of the last radiographic assessment was used.	Randomization until the date of disease progression or death (average of 26 weeks)	No
Primary	Time to Progression as Evaluated by the Independent Review Committee (IRC)	Time to progression is defined as the interval between the date of randomization and the earliest date of progression of disease (PD) or death due to breast cancer. The IRC assessed PD based on radiological PD (imaging data) and clinical symptomatic progress (Response Evaluation Criteria in Solid Tumors [RECIST] Criteria: target lesion (TL), at least a 20% increase in the sum of largest diameter (LD) of TLs or the appearance of one or more new lesions; non-TL (NTL), the appearance of one or more new lesions and/or unequivocal progression of existing NTLs). TTP was assessed in participants who died due to breast cancer or progressed, as assessed by the independent reviewer, as well as in those who were censored and completed follow-up and those who were censored but are still being followed. For censored participants (those without a documented date of disease progression/death due to breast cancer), the date of the last radiographic assessment was used.	Randomization until the date of disease progression or death (average of 26 weeks)	No
Secondary	Number of Participants With Tumor Response as Evaluated by the Investigator	The percentage of participants with tumor response is defined as those participants with measurable disease who achieved either a complete response (CR) or partial response (PR). The Response Evaluation Criteria in Solid Tumors (RECIST) was used to evaluate the measurability of tumor lesions, to determine target lesion (TLs) and non-target lesion (NTLs). CR (TLs and NTLs): the disappearance of all TLs and NTLs; PR (for TLs): at least a 30% decrease in the sum of the largest diameter (LD) of TLs, taking as a reference the Baseline sum LD; PR (for NTLs): persistence of one or more lesions.	Randomization until the date of disease progression or death (average of 26 weeks)	No
Secondary	Number of Participants With Tumor Response as Evaluated by the Independent Review Committee	The percentage of participants with tumor response is defined as those participants with measurable disease who achieved either a complete response (CR) or partial response (PR). The RECIST criteria was used to evaluate the measurability of tumor lesions, to determine target lesion (TLs) and non-target lesion (NTLs). CR (TLs and NTLs): the disappearance of all TLs and NTLs; PR (for TLs): at least a 30% decrease in the sum of the largest diameter (LD) of TLs, taking as a reference the Baseline sum LD; PR (for NTLs): persistence of one or more lesions.	Randomization until the date of disease progression or death (average of 26 weeks)	No
Secondary	Percentage of Participants With Clinical Benefit (CB) as Assessed by the Investigator	Percentage of participants. with CB is defined as the percentage of participants with evidence of CR (disappearance of all TLs and NTLs), PR (TLs: a >=30% decrease in the sum of the LD, taking as a reference the Baseline sum LD; NTLs: persistence of >=1 lesion), or stable disease (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD) for >=6 months based on RECIST criteria. PD for TL: a >=20% increase in the sum of the LD of TLs or the appearance of >=1 new lesion. PD for NTLs: the appearance of >=1 new lesion and/or unequivocal progression of existing NTLs.	Randomization until the date of disease progression or death (average of 26 weeks)	No
Secondary	Number of Participants With a Response of CR or PR by the Indicated Study Week	Time to response (TTR) is defined as the time from randomization until the first documented evidence of CR (disappearance of all TLs and NTLs) or PR (for TLs: a >=30% decrease in the sum of the LD of TLs, taking as a reference the Baseline sum LD; for NTLs: the persistence of >=1 lesion) (whichever status was recorded first). TTR data are displayed as the number of participants achieving a CR or PR by the indicated week. The investigator evaluated the TTR, and the analysis was based on responses confirmed at a repeat assessment, with the TTR taken as the first time the response was observed.	Weeks 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, and 72	No
Secondary	Duration of Response (DOR)	The investigator evaluated the DOR for the subset of participants who showed a CR (disappearance of all TLs and NTLs) or PR (TLs: a >=30% decrease in the sum of the LD of TLs, taking as a reference the Baseline sum LD; NTLs: persistence of >=1 lesion). DOR is defined as the time from the first documented evidence of PR or CR until the first documented sign of PD (TL: a >=20% increase in the sum of the LD of TLs or the appearance of >=1 new lesion; NTL: the appearance of >=1 new lesion and/or unequivocal progression of existing NTLs) or death due to breast cancer, if sooner.	From the time of the first documented complete or partial response until the first documented evidence of progression or death (average of 26 weeks)	No
Secondary	Progression-Free Survival (PFS)	PFS is defined as the interval between the date of randomization and the earliest date of progression disease (PD) or death due to any cause, if sooner. For TLs, progressive disease is defined as at least a 20% increase in the sum of the LD of TLs or the appearance of 1 or more new lesions. For NTLs, progressive disease is defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. par., participants.	Randomization until the date of disease progression or death (average of 26 weeks)	No
Secondary	Number of Participants Who Progressed or Died at or Prior to 6 Months, as a Measure of Six Months Progression-free Survival (PFS)	PFS is defined as the interval between the date of randomization and the earliest date of disease progression or death due to any cause, if sooner. Six months PFS is defined as PFS at six months from the time of randomization. Raw data for 6 months PFS are not available; thus, data are presented as the number of participants who progressed or died at or prior to 6 months. For TLs, progressive disease is defined asat least a 20% increase in the sum of the LD of TLs or the appearance of 1 or more new lesions. For NTLs, progressive disease is defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. PFS was assessed in participants who died or progressed, as well as in those who were censored and completed follow-up and those who were censored but are still being followed. For censored participants (those without a documented date of disease progression/death due to breast cancer), the date of the last radiographic assessment was used.	Randomization until the date of disease progression or death (average of 26 weeks)	No
Secondary	Overall Survival	Overall survival is defined as the time from randomization until death due to any cause.	Randomization until the date of death due to any cause (average of 24 months)	No
Secondary	Change From Baseline in Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Scores	The FACT-B questionnaire was designed to measure multidimensional quality of life (QOL) in participants with breast cancer. The physical and functional well-being subscale scores range from 0 to 28, based on 7 questions (each scored from 0 [not at all] to 4 [very much] for all subscales); the emotional and social/family well-being (1 question optional) subscale scores range from 0 to 24 (based on 6 questions), and the additional concerns subscale score ranges from 0 to 40, based on 10 questions. The FACT-B Total Score (0 [better QOL] to 144 [worse QOL]) is the sum of the subscale scores.	Baseline (Day 1); Weeks 9, 21, 33, and 45; Withdrawal	No
Secondary	Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire Scores	The FACT-G questionnaire was designed to measure multidimensional QOL in participants with cancer and includes subscales for physical, social/family, emotional, and functional well-being. The physical, social/family, and functional well-being subscale scores range from 0 to 28, based on responses to 7 questions (each question scored from 0 [not at all] to 4 [very much]); the emotional well-being subscale score ranges from 0 to 24, based on responses to 6 questions. The FACT-G Total Score (ranging from 0 [better QOL] to 108 [worse QOL]) is the sum of the subscale scores.	Baseline (Day 1); Weeks 9, 21, 33, and 45; Withdrawal	No
Secondary	Change From Baseline in Trial Outcome Index (TOI) Questionnaire Scores	The TOI questionnaire was designed to measure multidimensional QOL in participants with cancer and includes subscales for physical, functional well-being, and additional cancer concerns. The physical and functional well-being subscale scores range from 0 to 28, based on 7 questions (each question scored from 0 [not at all] to 4 [very much]); the breast cancer unweighted subscale scores range from 0 to 36, based on 9 questions. The total TOI score (ranging from 0 [better QOL] to 92 [worse QOL]) is the sum of the TOI subscale scores.	Baseline (Day 1); Weeks 9, 21, 33, and 45; Withdrawal	No
Secondary	Number of Participants With the Indicated ErbB2 Status at Baseline	The Press Laboratory collected tumor tissues of participants for ErbB2 testing. ErbB2 testing is done to detect breast cancer and predict its likely outcome. All samples were analyzed by the Press Laboratory. Participants were categorized as ErbB2 positive (overexpression of the ErbB2 gene), ErbB2 negative, and assay not done (which included participants with no available samples and those with inconclusive results). ErbB2 status is determined by immunohistochemistry (ICH) assay and fluorescence in situ hybridization (FISH) testing. Negative ErbB2 status is defined as 0 or 1+ by IHC, or as 2+ by IHC and FISH.	Baseline	No
Secondary	ErbB2 Ratio	The Press Laboratory collected tumor tissues of participants for biomarker testing. All samples were analyzed by the Press Laboratory. The ratio of ErbB2 gene signals to chromosome 17 signals, which indicates the progression of breast cancer, was calculated. Low levels of amplification (few copies) may have a ratio of 2-5, whereas high levels of amplification may have a ratio >10.	Baseline	No
Secondary	Number of Participants With the Indicated Immunohistochemistry (IHC) Results at Screening	The Press Laboratory tested tumor tissue samples (taken at Screening, prior to randomization to study treatment) to determine intra-tumoral expression levels of ErbB1, ErbB2, and other analytes associated with these pathways by IHC, the process of detecting antigens (e.g., proteins) in cells of a tissue section. The IHC assessment is expressed as: 0, no staining (no cancer cells); 1+, faint staining; 2+, weak to moderate complete staining; 3+, strong complete staining (many cancer cells). A status of "Assay not done" was assigned to participants with no available samples and to those with inconclusive results. If strong staining is observed, breast cancer that has high levels of HER2 expression (overexpression) is indicated. If moderate/weak staining is observed (IHC=2+), breast cancer that has low/moderate expression levels is indicated. When no staining is observed (IHC=0), breast cancer HER2 expression may be below the level of detection of the assay.	Screening (Day -1)	No
Secondary	Number of Participants With the Indicated ErbB2 Fluorescence in Situ Hybridization (FISH) Results	The Press Laboratory tested participants who were 2+ (weak to moderate complete staining) or 3+ (strong complete staining) for ErbB2 overexpression by IHC for ErbB2 gene amplification using the FISH assay. The results of the FISH assay can be ErbB2 gene "amplification" (increased number of copies of the ErbB2 gene) or "non-amplification" (not many copies of the ErbB2 gene). A status of "Assay not done" was assigned to those participants with no available samples and to those with inconclusive results (e.g., due to hybridization or staining problems).	Baseline	No
Secondary	Serum ErbB1 Concentration	The Quest Laboratory collected blood samples for quantitative determination of serum ErbB1. The results of serum monitoring were used to compare tumor response rates following randomized therapy.	Screening (Day-1) and Withdrawal (up to Study Week 129)	No
Secondary	Serum ErbB2 Concentration	The Quest Laboratory collected blood samples for quantitative determination of serum ErbB2. The results of serum monitoring were used to compare tumor response rates following randomized therapy.	Screening (Day-1) and Withdrawal (up to Study Week 129)	No
Secondary	Number of Participants With the Indicated Adverse Events (AEs) With a Maximum Toxicity Grade of 3 or 4	The severity of adverse events was graded per the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 3. Grades 1 through 5 have unique clinical descriptions of severity for each AE based on the following general guideline: Grade 1, Mild AE; Grade 2, Moderate AE; Grade 3, Severe AE; Grade 4, Life-threatening or disabling AE; Grade 5, death related to AE.	Baseline (Day 1) until 30 days after the last dose of randomized therapy (average of 26 weeks)	No