Clinical trial NCT00075270: Paclitaxel With / Without GW572016 (Lapatinib) As First Line Therapy For Women With Advanced Or Metastatic Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Neoplasms, Breast
Keywords: metastatic breast cancer
ErbB1
kinase inhibitor
ErbB2
EGFR
lapatinib
Her2-neu
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2004-01-09
Enrollment: 580
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Time to Progression as Evaluated by the Investigator
timeFrame: Randomization until the date of disease progression or death (average of 26 weeks)
measure: Time to Progression as Evaluated by the Independent Review Committee (IRC)
timeFrame: Randomization until the date of disease progression or death (average of 26 weeks)
Secondary outcomes:
measure: Number of Participants With Tumor Response as Evaluated by the Investigator
timeFrame: Randomization until the date of disease progression or death (average of 26 weeks)
measure: Number of Participants With Tumor Response as Evaluated by the Independent Review Committee
timeFrame: Randomization until the date of disease progression or death (average of 26 weeks)
measure: Percentage of Participants With Clinical Benefit (CB) as Assessed by the Investigator
timeFrame: Randomization until the date of disease progression or death (average of 26 weeks)
measure: Number of Participants With a Response of CR or PR by the Indicated Study Week
timeFrame: Weeks 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, and 72
measure: Duration of Response (DOR)
timeFrame: From the time of the first documented complete or partial response until the first documented evidence of progression or death (average of 26 weeks)
measure: Progression-Free Survival (PFS)
timeFrame: Randomization until the date of disease progression or death (average of 26 weeks)
measure: Number of Participants Who Progressed or Died at or Prior to 6 Months, as a Measure of Six Months Progression-free Survival (PFS)
timeFrame: Randomization until the date of disease progression or death (average of 26 weeks)
measure: Overall Survival
timeFrame: Randomization until the date of death due to any cause (average of 24 months)
measure: Change From Baseline in Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Scores
timeFrame: Baseline (Day 1); Weeks 9, 21, 33, and 45; Withdrawal
measure: Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire Scores
timeFrame: Baseline (Day 1); Weeks 9, 21, 33, and 45; Withdrawal
measure: Change From Baseline in Trial Outcome Index (TOI) Questionnaire Scores
timeFrame: Baseline (Day 1); Weeks 9, 21, 33, and 45; Withdrawal
measure: Number of Participants With the Indicated ErbB2 Status at Baseline
timeFrame: Baseline
measure: ErbB2 Ratio
timeFrame: Baseline
measure: Number of Participants With the Indicated Immunohistochemistry (IHC) Results at Screening
timeFrame: Screening (Day -1)
measure: Number of Participants With the Indicated ErbB2 Fluorescence in Situ Hybridization (FISH) Results
timeFrame: Baseline
measure: Serum ErbB1 Concentration
timeFrame: Screening (Day-1) and Withdrawal (up to Study Week 129)
measure: Serum ErbB2 Concentration
timeFrame: Screening (Day-1) and Withdrawal (up to Study Week 129)
measure: Number of Participants With the Indicated Adverse Events (AEs) With a Maximum Toxicity Grade of 3 or 4
timeFrame: Baseline (Day 1) until 30 days after the last dose of randomized therapy (average of 26 weeks)
Other outcomes:
Locations:
city: Tucson
country: United States
facility: GSK Investigational Site
state: Arizona
city: Hot Springs
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Jonesboro
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Fountain Valley
country: United States
facility: GSK Investigational Site
state: California
city: La Jolla
country: United States
facility: GSK Investigational Site
state: California
city: Rancho Mirage
country: United States
facility: GSK Investigational Site
state: California
city: Vallejo
country: United States
facility: GSK Investigational Site
state: California
city: Denver
country: United States
facility: GSK Investigational Site
state: Colorado
city: Boca Raton
country: United States
facility: GSK Investigational Site
state: Florida
city: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
city: Port St. Lucie
country: United States
facility: GSK Investigational Site
state: Florida
city: West Palm Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Marietta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Savannah
country: United States
facility: GSK Investigational Site
state: Georgia
city: Savannah
country: United States
facility: GSK Investigational Site
state: Georgia
city: Indianapolis
country: United States
facility: GSK Investigational Site
state: Indiana
city: Kansas City
country: United States
facility: GSK Investigational Site
state: Kansas
city: Metairie
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
city: Glen Burnie
country: United States
facility: GSK Investigational Site
state: Maryland
city: Springfield
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Duluth
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Robbinsdale
country: United States
facility: GSK Investigational Site
state: Minnesota
city: St. Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Voorhees
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Santa Fe
country: United States
facility: GSK Investigational Site
state: New Mexico
city: Nyack
country: United States
facility: GSK Investigational Site
state: New York
city: Syracuse
country: United States
facility: GSK Investigational Site
state: New York
city: Charlotte
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Greenville
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Fargo
country: United States
facility: GSK Investigational Site
state: North Dakota
city: Canton
country: United States
facility: GSK Investigational Site
state: Ohio
city: Portland
country: United States
facility: GSK Investigational Site
state: Oregon
city: Columbia
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Knoxville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Knoxville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Amarillo
country: United States
facility: GSK Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Burlington
country: United States
facility: GSK Investigational Site
state: Vermont
city: Norfolk
country: United States
facility: GSK Investigational Site
state: Virginia
city: Tacoma
country: United States
facility: GSK Investigational Site
state: Washington
city: Milwaukee
country: United States
facility: GSK Investigational Site
state: Wisconsin
city: Capital Federal
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Capital Federal
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Fitzroy
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Malvern
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Wodonga
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Nedlands
country: Australia
facility: GSK Investigational Site
state: Western Australia
city: Vienna
country: Austria
facility: GSK Investigational Site
city: Brugge
country: Belgium
facility: GSK Investigational Site
city: Brussels
country: Belgium
facility: GSK Investigational Site
city: Brussel
country: Belgium
facility: GSK Investigational Site
city: Kortrijk
country: Belgium
facility: GSK Investigational Site
city: Leuven
country: Belgium
facility: GSK Investigational Site
city: Roeselare
country: Belgium
facility: GSK Investigational Site
city: Salvador
country: Brazil
facility: GSK Investigational Site
state: Bahía
city: Rio de Janeiro
country: Brazil
facility: GSK Investigational Site
city: Saint John's
country: Canada
facility: GSK Investigational Site
state: Newfoundland and Labrador
city: Sudbury
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Thunder Bay
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Sherbrooke
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Santiago
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Santiago
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Santiago
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Brno
country: Czech Republic
facility: GSK Investigational Site
city: Hradec Kralove
country: Czech Republic
facility: GSK Investigational Site
city: Olomouc
country: Czech Republic
facility: GSK Investigational Site
city: Aalen
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Stuttgart
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Ulm
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Augsburg
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Bayreuth
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Coburg
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Fuerstenwalde
country: Germany
facility: GSK Investigational Site
state: Brandenburg
city: Stade
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Herne
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Ibbenbueren
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Muenster
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Halle
country: Germany
facility: GSK Investigational Site
state: Sachsen-Anhalt
city: Kiel
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Jena
country: Germany
facility: GSK Investigational Site
state: Thueringen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Budapest
country: Hungary
facility: GSK Investigational Site
city: Nyíregyháza
country: Hungary
facility: GSK Investigational Site
city: Szombathely
country: Hungary
facility: GSK Investigational Site
city: Zalaegerszeg-Pózva
country: Hungary
facility: GSK Investigational Site
city: Benevento
country: Italy
facility: GSK Investigational Site
state: Campania
city: Napoli
country: Italy
facility: GSK Investigational Site
state: Campania
city: Forlì
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Parma
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Ravenna
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Rimini
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Roma
country: Italy
facility: GSK Investigational Site
state: Lazio
city: Roma
country: Italy
facility: GSK Investigational Site
state: Lazio
city: Pietra Ligure (SV)
country: Italy
facility: GSK Investigational Site
state: Liguria
city: Bergamo
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Pavia
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Candiolo (TO)
country: Italy
facility: GSK Investigational Site
state: Piemonte
city: Torino
country: Italy
facility: GSK Investigational Site
state: Piemonte
city: Sassari
country: Italy
facility: GSK Investigational Site
state: Sardegna
city: Prato (PO)
country: Italy
facility: GSK Investigational Site
state: Toscana
city: Perugia
country: Italy
facility: GSK Investigational Site
state: Umbria
city: Gyeonggi-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Daugavpils
country: Latvia
facility: GSK Investigational Site
city: Liepaja
country: Latvia
facility: GSK Investigational Site
city: Riga
country: Latvia
facility: GSK Investigational Site
city: Riga
country: Latvia
facility: GSK Investigational Site
city: Acapulco
country: Mexico
facility: GSK Investigational Site
state: Guerrero
city: Guadalajara
country: Mexico
facility: GSK Investigational Site
state: Jalisco
city: Colima
country: Mexico
facility: GSK Investigational Site
city: Durango
country: Mexico
facility: GSK Investigational Site
city: Amersfoort
country: Netherlands
facility: GSK Investigational Site
city: Leiden
country: Netherlands
facility: GSK Investigational Site
city: Nieuwegein
country: Netherlands
facility: GSK Investigational Site
city: Utrecht
country: Netherlands
facility: GSK Investigational Site
city: Utrecht
country: Netherlands
facility: GSK Investigational Site
city: Auckland
country: New Zealand
facility: GSK Investigational Site
city: Christchurch
country: New Zealand
facility: GSK Investigational Site
city: Lahore
country: Pakistan
facility: GSK Investigational Site
city: Lahore
country: Pakistan
facility: GSK Investigational Site
city: Callao
country: Peru
facility: GSK Investigational Site
city: Lima
country: Peru
facility: GSK Investigational Site
city: Krakow
country: Poland
facility: GSK Investigational Site
city: Olsztyn
country: Poland
facility: GSK Investigational Site
city: Olsztyn
country: Poland
facility: GSK Investigational Site
city: Poznan
country: Poland
facility: GSK Investigational Site
city: Warszawa
country: Poland
facility: GSK Investigational Site
city: Wroclaw
country: Poland
facility: GSK Investigational Site
city: Moscow Region
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: St. Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: St. Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Banska Bystrica
country: Slovakia
facility: GSK Investigational Site
city: Bratislava
country: Slovakia
facility: GSK Investigational Site
city: Kosice
country: Slovakia
facility: GSK Investigational Site
city: Poprad
country: Slovakia
facility: GSK Investigational Site
city: Parktown
country: South Africa
facility: GSK Investigational Site
state: Gauteng
city: Capital Park
country: South Africa
facility: GSK Investigational Site
city: Overport
country: South Africa
facility: GSK Investigational Site
city: Parow
country: South Africa
facility: GSK Investigational Site
city: Port Elizabeth
country: South Africa
facility: GSK Investigational Site
city: Alcorcón/Madrid
country: Spain
facility: GSK Investigational Site
city: Baracaldo/Vizcaya
country: Spain
facility: GSK Investigational Site
city: Caceres
country: Spain
facility: GSK Investigational Site
city: Cuidad Real
country: Spain
facility: GSK Investigational Site
city: Jaen
country: Spain
facility: GSK Investigational Site
city: La Laguna (Santa Cruz de Tenerife)
country: Spain
facility: GSK Investigational Site
city: Las Palmas De Gran Canaria
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Móstoles/Madrid
country: Spain
facility: GSK Investigational Site
city: Palma de Mallorca
country: Spain
facility: GSK Investigational Site
city: Pontevedra
country: Spain
facility: GSK Investigational Site
city: San Sebastián
country: Spain
facility: GSK Investigational Site
city: Santa Cruz de Tenerife
country: Spain
facility: GSK Investigational Site
city: Zaragoza
country: Spain
facility: GSK Investigational Site
city: Zaragoza
country: Spain
facility: GSK Investigational Site
city: Istanbul
country: Turkey
facility: GSK Investigational Site
city: Istanbul
country: Turkey
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.