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

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

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.

Study Overview

• Status: Completed
• Conditions: Neoplasms, Breast
• Intervention / Treatment: Drug: Paclitaxel; Drug: GW572016 (Lapatinib)

• Study Type: Interventional
• Enrollment (Actual): 580
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1425
    • GSK Investigational Site
  • Buenos Aires
    • Capital Federal, Buenos Aires, Argentina, C1426ANZ
      • GSK Investigational Site
    • Capital Federal, Buenos Aires, Argentina, C1405CBA
      • GSK Investigational Site
• Australia
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • GSK Investigational Site
    • Malvern, Victoria, Australia, 3144
      • GSK Investigational Site
    • Wodonga, Victoria, Australia, 3690
      • GSK Investigational Site
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • GSK Investigational Site
• Austria
  • Vienna, Austria, A-1090
    • GSK Investigational Site
• Belgium
  • Brugge, Belgium, 8000
    • GSK Investigational Site
  • Brussel, Belgium, 1090
    • GSK Investigational Site
  • Brussels, Belgium, 1070
    • GSK Investigational Site
  • Kortrijk, Belgium, 8500
    • GSK Investigational Site
  • Leuven, Belgium, 3000
    • GSK Investigational Site
  • Roeselare, Belgium, 8800
    • GSK Investigational Site
• Brazil
  • Rio de Janeiro, Brazil, 20560-120
    • GSK Investigational Site
  • Bahía
    • Salvador, Bahía, Brazil, 41825-010
      • GSK Investigational Site
• Canada
  • Newfoundland and Labrador
    • Saint John's, Newfoundland and Labrador, Canada, A1B 3V6
      • GSK Investigational Site
  • Ontario
    • Sudbury, Ontario, Canada, P3E 5J1
      • GSK Investigational Site
    • Thunder Bay, Ontario, Canada, P7B 6V4
      • GSK Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H4J 1C5
      • GSK Investigational Site
    • Montreal, Quebec, Canada, H3T 1E2
      • GSK Investigational Site
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • GSK Investigational Site
• Chile
  • Región Metro De Santiago
    • Santiago, Región Metro De Santiago, Chile
      • GSK Investigational Site
    • Santiago, Región Metro De Santiago, Chile, 7500921
      • GSK Investigational Site
    • Santiago, Región Metro De Santiago, Chile, 7591046
      • GSK Investigational Site
• Czech Republic
  • Brno, Czech Republic, 656 53
    • GSK Investigational Site
  • Hradec Kralove, Czech Republic, 500 05
    • GSK Investigational Site
  • Olomouc, Czech Republic, 775 20
    • GSK Investigational Site
• Germany
  • Berlin, Germany, 10367
    • GSK Investigational Site
  • Berlin, Germany, 10117
    • GSK Investigational Site
  • Berlin, Germany, 13353
    • GSK Investigational Site
  • Berlin, Germany, 14195
    • GSK Investigational Site
  • Hamburg, Germany, 22457
    • GSK Investigational Site
  • Hamburg, Germany, 20259
    • GSK Investigational Site
  • Hamburg, Germany, 22767
    • GSK Investigational Site
  • Baden-Wuerttemberg
    • Aalen, Baden-Wuerttemberg, Germany, 73428
      • GSK Investigational Site
    • Stuttgart, Baden-Wuerttemberg, Germany, 70190
      • GSK Investigational Site
    • Ulm, Baden-Wuerttemberg, Germany, 89075
      • GSK Investigational Site
  • Bayern
    • Augsburg, Bayern, Germany, 86150
      • GSK Investigational Site
    • Bayreuth, Bayern, Germany, 95445
      • GSK Investigational Site
    • Coburg, Bayern, Germany, 96450
      • GSK Investigational Site
    • Muenchen, Bayern, Germany, 80335
      • GSK Investigational Site
    • Muenchen, Bayern, Germany, 80637
      • GSK Investigational Site
  • Brandenburg
    • Fuerstenwalde, Brandenburg, Germany, 15517
      • GSK Investigational Site
  • Niedersachsen
    • Stade, Niedersachsen, Germany, 21680
      • GSK Investigational Site
  • Nordrhein-Westfalen
    • Herne, Nordrhein-Westfalen, Germany, 44625
      • GSK Investigational Site
    • Ibbenbueren, Nordrhein-Westfalen, Germany, 49477
      • GSK Investigational Site
    • Muenster, Nordrhein-Westfalen, Germany, 48149
      • GSK Investigational Site
  • Sachsen-Anhalt
    • Halle, Sachsen-Anhalt, Germany, 06120
      • GSK Investigational Site
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24103
      • GSK Investigational Site
  • Thueringen
    • Jena, Thueringen, Germany, 07743
      • GSK Investigational Site
• Hungary
  • Budapest, Hungary, 1082
    • GSK Investigational Site
  • Nyíregyháza, Hungary, 4400
    • GSK Investigational Site
  • Szombathely, Hungary, 9700
    • GSK Investigational Site
  • Zalaegerszeg-Pózva, Hungary, 8900
    • GSK Investigational Site
• Italy
  • Campania
    • Benevento, Campania, Italy, 82100
      • GSK Investigational Site
    • Napoli, Campania, Italy, 80131
      • GSK Investigational Site
  • Emilia-Romagna
    • Forlì, Emilia-Romagna, Italy, 47100
      • GSK Investigational Site
    • Parma, Emilia-Romagna, Italy, 43100
      • GSK Investigational Site
    • Ravenna, Emilia-Romagna, Italy, 48100
      • GSK Investigational Site
    • Rimini, Emilia-Romagna, Italy, 47900
      • GSK Investigational Site
  • Lazio
    • Roma, Lazio, Italy, 00152
      • GSK Investigational Site
    • Roma, Lazio, Italy, 00157
      • GSK Investigational Site
  • Liguria
    • Pietra Ligure (SV), Liguria, Italy, 17027
      • GSK Investigational Site
  • Lombardia
    • Bergamo, Lombardia, Italy, 24128
      • GSK Investigational Site
    • Pavia, Lombardia, Italy, 27100
      • GSK Investigational Site
  • Piemonte
    • Candiolo (TO), Piemonte, Italy, 10060
      • GSK Investigational Site
    • Torino, Piemonte, Italy, 10153
      • GSK Investigational Site
  • Sardegna
    • Sassari, Sardegna, Italy, 07100
      • GSK Investigational Site
  • Toscana
    • Prato (PO), Toscana, Italy, 59100
      • GSK Investigational Site
  • Umbria
    • Perugia, Umbria, Italy, 06122
      • GSK Investigational Site
• Korea, Republic of
  • Gyeonggi-do, Korea, Republic of, 411-769
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 135-710
    • GSK Investigational Site
• Latvia
  • Daugavpils, Latvia, LV5420
    • GSK Investigational Site
  • Liepaja, Latvia, LV3401
    • GSK Investigational Site
  • Riga, Latvia, LV 1002
    • GSK Investigational Site
  • Riga, Latvia, LV 1079
    • GSK Investigational Site
• Mexico
  • Colima, Mexico, 28010
    • GSK Investigational Site
  • Durango, Mexico, 34000
    • GSK Investigational Site
  • Guerrero
    • Acapulco, Guerrero, Mexico, 39670
      • GSK Investigational Site
  • Jalisco
    • Guadalajara, Jalisco, Mexico, CP44280
      • GSK Investigational Site
• Netherlands
  • Amersfoort, Netherlands, 3816 CP
    • GSK Investigational Site
  • Leiden, Netherlands, 2333 ZA
    • GSK Investigational Site
  • Nieuwegein, Netherlands, 3435 CM
    • GSK Investigational Site
  • Utrecht, Netherlands, 2584 CX
    • GSK Investigational Site
  • Utrecht, Netherlands, 3584 CX
    • GSK Investigational Site
• New Zealand
  • Auckland, New Zealand, 1001
    • GSK Investigational Site
  • Christchurch, New Zealand, 8001
    • GSK Investigational Site
• Pakistan
  • Lahore, Pakistan, 54000
    • GSK Investigational Site
  • Lahore, Pakistan
    • GSK Investigational Site
• Peru
  • Callao, Peru, Callao 2
    • GSK Investigational Site
  • Lima, Peru, Lima 34
    • GSK Investigational Site
• Poland
  • Krakow, Poland, 31-826
    • GSK Investigational Site
  • Olsztyn, Poland, 10-228
    • GSK Investigational Site
  • Olsztyn, Poland, 10-226
    • GSK Investigational Site
  • Poznan, Poland, 61-866
    • GSK Investigational Site
  • Warszawa, Poland, 02-781
    • GSK Investigational Site
  • Wroclaw, Poland, 53-413
    • GSK Investigational Site
• Russian Federation
  • Moscow, Russian Federation, 117997
    • GSK Investigational Site
  • Moscow, Russian Federation, 115 478
    • GSK Investigational Site
  • Moscow, Russian Federation, 129 128
    • GSK Investigational Site
  • Moscow, Russian Federation, 129301
    • GSK Investigational Site
  • Moscow, Russian Federation, 105005
    • GSK Investigational Site
  • Moscow Region, Russian Federation, 143 423
    • GSK Investigational Site
  • St. Petersburg, Russian Federation, 197022
    • GSK Investigational Site
  • St. Petersburg, Russian Federation, 197758
    • GSK Investigational Site
• Slovakia
  • Banska Bystrica, Slovakia, 975 17
    • GSK Investigational Site
  • Bratislava, Slovakia, 833 10
    • GSK Investigational Site
  • Kosice, Slovakia, 041 91
    • GSK Investigational Site
  • Poprad, Slovakia, 058 01
    • GSK Investigational Site
• South Africa
  • Capital Park, South Africa, 0002
    • GSK Investigational Site
  • Overport, South Africa, 4001
    • GSK Investigational Site
  • Parow, South Africa, 7525
    • GSK Investigational Site
  • Port Elizabeth, South Africa, 6001
    • GSK Investigational Site
  • Gauteng
    • Parktown, Gauteng, South Africa, 2193
      • GSK Investigational Site
• Spain
  • Alcorcón/Madrid, Spain, 28922
    • GSK Investigational Site
  • Baracaldo/Vizcaya, Spain, 48903
    • GSK Investigational Site
  • Caceres, Spain, 10003
    • GSK Investigational Site
  • Cuidad Real, Spain, 13002
    • GSK Investigational Site
  • Jaen, Spain, 23007
    • GSK Investigational Site
  • La Laguna (Santa Cruz de Tenerife), Spain, 38320
    • GSK Investigational Site
  • Las Palmas De Gran Canaria, Spain, 35016
    • GSK Investigational Site
  • Madrid, Spain, 28035
    • GSK Investigational Site
  • Móstoles/Madrid, Spain, 28935
    • GSK Investigational Site
  • Palma de Mallorca, Spain, 07014
    • GSK Investigational Site
  • Pontevedra, Spain, 36071
    • GSK Investigational Site
  • San Sebastián, Spain, 20014
    • GSK Investigational Site
  • Santa Cruz de Tenerife, Spain, 38320
    • GSK Investigational Site
  • Zaragoza, Spain, 50009
    • GSK Investigational Site
  • Zaragoza, Spain
    • GSK Investigational Site
• Turkey
  • Istanbul, Turkey
    • GSK Investigational Site
  • Istanbul, Turkey, 34865
    • GSK Investigational Site
• United States
  • Arizona
    • Tucson, Arizona, United States, 85712
      • GSK Investigational Site
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • GSK Investigational Site
    • Jonesboro, Arkansas, United States, 72401
      • GSK Investigational Site
  • California
    • Fountain Valley, California, United States, 92708
      • GSK Investigational Site
    • La Jolla, California, United States, 92093-0987
      • GSK Investigational Site
    • Rancho Mirage, California, United States, 92270
      • GSK Investigational Site
    • Vallejo, California, United States, 94589
      • GSK Investigational Site
  • Colorado
    • Denver, Colorado, United States, 80218
      • GSK Investigational Site
  • Florida
    • Boca Raton, Florida, United States, 33486
      • GSK Investigational Site
    • Orlando, Florida, United States, 32804
      • GSK Investigational Site
    • Port St. Lucie, Florida, United States, 34952
      • GSK Investigational Site
    • West Palm Beach, Florida, United States, 33401
      • GSK Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30341
      • GSK Investigational Site
    • Marietta, Georgia, United States, 30060
      • GSK Investigational Site
    • Savannah, Georgia, United States, 31405
      • GSK Investigational Site
    • Savannah, Georgia, United States, 31406
      • GSK Investigational Site
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • GSK Investigational Site
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • GSK Investigational Site
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • GSK Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • GSK Investigational Site
    • Glen Burnie, Maryland, United States, 21225
      • GSK Investigational Site
  • Massachusetts
    • Springfield, Massachusetts, United States, 01199
      • GSK Investigational Site
  • Minnesota
    • Duluth, Minnesota, United States, 55802
      • GSK Investigational Site
    • Robbinsdale, Minnesota, United States, 55422
      • GSK Investigational Site
  • Missouri
    • St. Louis, Missouri, United States, 63141
      • GSK Investigational Site
  • New Jersey
    • Voorhees, New Jersey, United States, 08043
      • GSK Investigational Site
  • New Mexico
    • Santa Fe, New Mexico, United States, 87505
      • GSK Investigational Site
  • New York
    • Nyack, New York, United States, 10960
      • GSK Investigational Site
    • Syracuse, New York, United States, 13210
      • GSK Investigational Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • GSK Investigational Site
    • Greenville, North Carolina, United States, 27834
      • GSK Investigational Site
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • GSK Investigational Site
  • Ohio
    • Canton, Ohio, United States, 44718
      • GSK Investigational Site
  • Oregon
    • Portland, Oregon, United States, 97227
      • GSK Investigational Site
  • South Carolina
    • Columbia, South Carolina, United States, 29210
      • GSK Investigational Site
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • GSK Investigational Site
    • Knoxville, Tennessee, United States, 37916
      • GSK Investigational Site
  • Texas
    • Amarillo, Texas, United States, 79106
      • GSK Investigational Site
    • Fort Worth, Texas, United States, 76104
      • GSK Investigational Site
    • Houston, Texas, United States, 77054
      • GSK Investigational Site
    • San Antonio, Texas, United States, 78229
      • GSK Investigational Site
  • Vermont
    • Burlington, Vermont, United States, 05401
      • GSK Investigational Site
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • GSK Investigational Site
  • Washington
    • Tacoma, Washington, United States, 98405
      • GSK Investigational Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Lapatinib 1500 mg, once daily and Paclitaxel 175 mg/m Intravenously over 3 hours ever 3 weeks	Drug: Paclitaxel; Active Comparator; Drug: GW572016 (Lapatinib); Oral GW572016 Lapatinib; Other Names: Paclitaxel
Placebo Comparator: Arm 2; Paclitaxel 175 mg/m Intravenously over 3 hours ever 3 weeks and Placebo	Drug: Paclitaxel; Active Comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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
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)
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)
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)
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)
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
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
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
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
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
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)
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
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)
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)
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)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Tenori L, Oakman C, Claudino WM, Bernini P, Cappadona S, Nepi S, Biganzoli L, Arbushites MC, Luchinat C, Bertini I, Di Leo A. Exploration of serum metabolomic profiles and outcomes in women with metastatic breast cancer: a pilot study. Mol Oncol. 2012 Aug;6(4):437-44. doi: 10.1016/j.molonc.2012.05.003. Epub 2012 Jun 1.
• 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.
• Sherrill B, Di Leo A, Amonkar MM, Wu Y, Zvirbule Z, Aziz Z, Bines J, Gomez HL. Quality-of-life and quality-adjusted survival (Q-TWiST) in patients receiving lapatinib in combination with paclitaxel as first-line treatment for metastatic breast cancer. Curr Med Res Opin. 2010 Apr;26(4):767-75. doi: 10.1185/03007991003590860.

Study record dates

Study Major Dates

• Study Start: January 1, 2004
• Primary Completion (Actual): October 1, 2006
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: January 7, 2004
• First Submitted That Met QC Criteria: January 8, 2004
• First Posted (Estimate): January 9, 2004

Study Record Updates

• Last Update Posted (Estimate): May 6, 2015
• Last Update Submitted That Met QC Criteria: April 16, 2015
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: EGFR; lapatinib; kinase inhibitor; metastatic breast cancer; ErbB1; ErbB2; Her2-neu
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Protein Kinase Inhibitors; Paclitaxel; Albumin-Bound Paclitaxel; Lapatinib
• Other Study ID Numbers: EGF30001