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

NCT00075270 | Completed Phase 3 Results

• 1 other identifier: EGF30001
• Study Type: interventional
• Target: 580
• Locations: 24 countries
• Sites: 173

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.

Conditions

Neoplasms, Breast

Keywords

metastatic breast cancer; ErbB1; kinase inhibitor; ErbB2; EGFR; lapatinib; Her2-neu

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (18)

• Number of Participants With Tumor Response as Evaluated by the Investigator

  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

  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

  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

  Weeks 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, and 72

• Duration of Response (DOR)

  From the time of the first documented complete or partial response until the first documented evidence of progression or death (average of 26 weeks)

Study Arms (2)

Arm 1

EXPERIMENTAL

Lapatinib 1500 mg, once daily and Paclitaxel 175 mg/m Intravenously over 3 hours ever 3 weeks

Drug: Paclitaxel; Drug: GW572016 (Lapatinib)

Arm 2

PLACEBO COMPARATOR

Paclitaxel 175 mg/m Intravenously over 3 hours ever 3 weeks and Placebo

Drug: Paclitaxel

Interventions

Paclitaxel DRUG

Active Comparator

Arm 1; Arm 2

GW572016 (Lapatinib) DRUG

Oral GW572016 Lapatinib

Also known as: Paclitaxel

Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (177)

GSK Investigational Site

Tucson, Arizona, 85712, United States

Location

GSK Investigational Site

Hot Springs, Arkansas, 71913, United States

Location

GSK Investigational Site

Jonesboro, Arkansas, 72401, United States

Location

GSK Investigational Site

Fountain Valley, California, 92708, United States

Location

GSK Investigational Site

La Jolla, California, 92093-0987, United States

Location

GSK Investigational Site

Rancho Mirage, California, 92270, United States

Location

GSK Investigational Site

Vallejo, California, 94589, United States

Location

GSK Investigational Site

Denver, Colorado, 80218, United States

Location

GSK Investigational Site

Boca Raton, Florida, 33486, United States

Location

GSK Investigational Site

Orlando, Florida, 32804, United States

Location

GSK Investigational Site

Port Saint Lucie, Florida, 34952, United States

Location

GSK Investigational Site

West Palm Beach, Florida, 33401, United States

Location

GSK Investigational Site

Atlanta, Georgia, 30341, United States

Location

GSK Investigational Site

Marietta, Georgia, 30060, United States

Location

GSK Investigational Site

Savannah, Georgia, 31405, United States

Location

GSK Investigational Site

Savannah, Georgia, 31406, United States

Location

GSK Investigational Site

Indianapolis, Indiana, 46260, United States

Location

GSK Investigational Site

Kansas City, Kansas, 66160, United States

Location

GSK Investigational Site

Metairie, Louisiana, 70006, United States

Location

GSK Investigational Site

Baltimore, Maryland, 21201, United States

Location

GSK Investigational Site

Glen Burnie, Maryland, 21225, United States

Location

GSK Investigational Site

Springfield, Massachusetts, 01199, United States

Location

GSK Investigational Site

Duluth, Minnesota, 55802, United States

Location

GSK Investigational Site

Robbinsdale, Minnesota, 55422, United States

Location

GSK Investigational Site

St Louis, Missouri, 63141, United States

Location

GSK Investigational Site

Voorhees Township, New Jersey, 08043, United States

Location

GSK Investigational Site

Santa Fe, New Mexico, 87505, United States

Location

GSK Investigational Site

Nyack, New York, 10960, United States

Location

GSK Investigational Site

Syracuse, New York, 13210, United States

Location

GSK Investigational Site

Charlotte, North Carolina, 28203, United States

Location

GSK Investigational Site

Greenville, North Carolina, 27834, United States

Location

GSK Investigational Site

Fargo, North Dakota, 58103, United States

Location

GSK Investigational Site

Canton, Ohio, 44718, United States

Location

GSK Investigational Site

Portland, Oregon, 97227, United States

Location

GSK Investigational Site

Columbia, South Carolina, 29210, United States

Location

GSK Investigational Site

Knoxville, Tennessee, 37916, United States

Location

GSK Investigational Site

Knoxville, Tennessee, 37920, United States

Location

GSK Investigational Site

Amarillo, Texas, 79106, United States

Location

GSK Investigational Site

Fort Worth, Texas, 76104, United States

Location

GSK Investigational Site

Houston, Texas, 77054, United States

Location

GSK Investigational Site

San Antonio, Texas, 78229, United States

Location

GSK Investigational Site

Burlington, Vermont, 05401, United States

Location

GSK Investigational Site

Norfolk, Virginia, 23502, United States

Location

GSK Investigational Site

Tacoma, Washington, 98405, United States

Location

GSK Investigational Site

Milwaukee, Wisconsin, 53226, United States

Location

GSK Investigational Site

Buenos Aires, Buenos Aires, 1425, Argentina

Location

GSK Investigational Site

Capital Federal, Buenos Aires, C1405CBA, Argentina

Location

GSK Investigational Site

Capital Federal, Buenos Aires, C1426ANZ, Argentina

Location

GSK Investigational Site

Fitzroy, Victoria, 3065, Australia

Location

GSK Investigational Site

Malvern, Victoria, 3144, Australia

Location

GSK Investigational Site

Wodonga, Victoria, 3690, Australia

Location

GSK Investigational Site

Nedlands, Western Australia, 6009, Australia

Location

GSK Investigational Site

Vienna, A-1090, Austria

Location

GSK Investigational Site

Bruges, 8000, Belgium

Location

GSK Investigational Site

Brussels, 1070, Belgium

Location

GSK Investigational Site

Brussels, 1090, Belgium

Location

GSK Investigational Site

Kortrijk, 8500, Belgium

Location

GSK Investigational Site

Leuven, 3000, Belgium

Location

GSK Investigational Site

Roeselare, 8800, Belgium

Location

GSK Investigational Site

Salvador, Estado de Bahia, 41825-010, Brazil

Location

GSK Investigational Site

Rio de Janeiro, Rio de Janeiro, 20560-120, Brazil

Location

GSK Investigational Site

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

Location

GSK Investigational Site

Greater Sudbury, Ontario, P3E 5J1, Canada

Location

GSK Investigational Site

Thunder Bay, Ontario, P7B 6V4, Canada

Location

GSK Investigational Site

Montreal, Quebec, H3T 1E2, Canada

Location

GSK Investigational Site

Montreal, Quebec, H4J 1C5, Canada

Location

GSK Investigational Site

Sherbrooke, Quebec, J1H 5N4, Canada

Location

GSK Investigational Site

Santiago, Región Metro de Santiago, 7500921, Chile

Location

GSK Investigational Site

Santiago, Región Metro de Santiago, 7591046, Chile

Location

GSK Investigational Site

Santiago, Región Metro de Santiago, Chile

Location

GSK Investigational Site

Brno, 656 53, Czechia

Location

GSK Investigational Site

Hradec Králové, 500 05, Czechia

Location

GSK Investigational Site

Olomouc, 775 20, Czechia

Location

GSK Investigational Site

Aalen, Baden-Wurttemberg, 73428, Germany

Location

GSK Investigational Site

Stuttgart, Baden-Wurttemberg, 70190, Germany

Location

GSK Investigational Site

Ulm, Baden-Wurttemberg, 89075, Germany

Location

GSK Investigational Site

Augsburg, Bavaria, 86150, Germany

Location

GSK Investigational Site

Bayreuth, Bavaria, 95445, Germany

Location

GSK Investigational Site

Coburg, Bavaria, 96450, Germany

Location

GSK Investigational Site

Munich, Bavaria, 80335, Germany

Location

GSK Investigational Site

Munich, Bavaria, 80637, Germany

Location

GSK Investigational Site

Fürstenwalde, Brandenburg, 15517, Germany

Location

GSK Investigational Site

Hamburg, Hamburg, 20259, Germany

Location

GSK Investigational Site

Hamburg, Hamburg, 22457, Germany

Location

GSK Investigational Site

Hamburg, Hamburg, 22767, Germany

Location

GSK Investigational Site

Stade, Lower Saxony, 21680, Germany

Location

GSK Investigational Site

Herne, North Rhine-Westphalia, 44625, Germany

Location

GSK Investigational Site

Ibbenbueren, North Rhine-Westphalia, 49477, Germany

Location

GSK Investigational Site

Münster, North Rhine-Westphalia, 48149, Germany

Location

GSK Investigational Site

Halle, Saxony-Anhalt, 06120, Germany

Location

GSK Investigational Site

Kiel, Schleswig-Holstein, 24103, Germany

Location

GSK Investigational Site

Berlin, State of Berlin, 10117, Germany

Location

GSK Investigational Site

Berlin, State of Berlin, 10367, Germany

Location

GSK Investigational Site

Berlin, State of Berlin, 13353, Germany

Location

GSK Investigational Site

Berlin, State of Berlin, 14195, Germany

Location

GSK Investigational Site

Jena, Thuringia, 07743, Germany

Location

GSK Investigational Site

Budapest, 1082, Hungary

Location

GSK Investigational Site

Nyíregyháza, 4400, Hungary

Location

GSK Investigational Site

Szombathely, 9700, Hungary

Location

GSK Investigational Site

Zalaegerszeg-Pózva, 8900, Hungary

Location

GSK Investigational Site

Benevento, Campania, 82100, Italy

Location

GSK Investigational Site

Napoli, Campania, 80131, Italy

Location

GSK Investigational Site

Forlì, Emilia-Romagna, 47100, Italy

Location

GSK Investigational Site

Parma, Emilia-Romagna, 43100, Italy

Location

GSK Investigational Site

Ravenna, Emilia-Romagna, 48100, Italy

Location

GSK Investigational Site

Rimini, Emilia-Romagna, 47900, Italy

Location

GSK Investigational Site

Rome, Lazio, 00152, Italy

Location

GSK Investigational Site

Rome, Lazio, 00157, Italy

Location

GSK Investigational Site

Pietra Ligure (SV), Liguria, 17027, Italy

Location

GSK Investigational Site

Bergamo, Lombardy, 24128, Italy

Location

GSK Investigational Site

Pavia, Lombardy, 27100, Italy

Location

GSK Investigational Site

Candiolo (TO), Piedmont, 10060, Italy

Location

GSK Investigational Site

Turin, Piedmont, 10153, Italy

Location

GSK Investigational Site

Sassari, Sardinia, 07100, Italy

Location

GSK Investigational Site

Prato (PO), Tuscany, 59100, Italy

Location

GSK Investigational Site

Perugia, Umbria, 06122, Italy

Location

GSK Investigational Site

Daugavpils, LV5420, Latvia

Location

GSK Investigational Site

Liepāja, LV3401, Latvia

Location

GSK Investigational Site

Riga, LV 1002, Latvia

Location

GSK Investigational Site

Riga, LV 1079, Latvia

Location

GSK Investigational Site

Colima, Colima, 28010, Mexico

Location

GSK Investigational Site

Durango, Durango, 34000, Mexico

Location

GSK Investigational Site

Acapulco de Juárez, Guerrero, 39670, Mexico

Location

GSK Investigational Site

Guadalajara, Jalisco, CP44280, Mexico

Location

GSK Investigational Site

Amersfoort, 3816 CP, Netherlands

Location

GSK Investigational Site

Leiden, 2333 ZA, Netherlands

Location

GSK Investigational Site

Nieuwegein, 3435 CM, Netherlands

Location

GSK Investigational Site

Utrecht, 2584 CX, Netherlands

Location

GSK Investigational Site

Utrecht, 3584 CX, Netherlands

Location

GSK Investigational Site

Auckland, 1001, New Zealand

Location

GSK Investigational Site

Christchurch, 8001, New Zealand

Location

GSK Investigational Site

Lahore, 54000, Pakistan

Location

GSK Investigational Site

Lahore, Pakistan

Location

GSK Investigational Site

Lima, Lima Province, Lima 34, Peru

Location

GSK Investigational Site

Callao, Callao 2, Peru

Location

GSK Investigational Site

Krakow, 31-826, Poland

Location

GSK Investigational Site

Olsztyn, 10-226, Poland

Location

GSK Investigational Site

Olsztyn, 10-228, Poland

Location

GSK Investigational Site

Poznan, 61-866, Poland

Location

GSK Investigational Site

Warsaw, 02-781, Poland

Location

GSK Investigational Site

Wroclaw, 53-413, Poland

Location

GSK Investigational Site

Moscow, 105005, Russia

Location

GSK Investigational Site

Moscow, 115 478, Russia

Location

GSK Investigational Site

Moscow, 117997, Russia

Location

GSK Investigational Site

Moscow, 129 128, Russia

Location

GSK Investigational Site

Moscow, 129301, Russia

Location

GSK Investigational Site

Moscow Region, 143 423, Russia

Location

GSK Investigational Site

Saint Petersburg, 197022, Russia

Location

GSK Investigational Site

Saint Petersburg, 197758, Russia

Location

GSK Investigational Site

Banská Bystrica, 975 17, Slovakia

Location

GSK Investigational Site

Bratislava, 833 10, Slovakia

Location

GSK Investigational Site

Košice, 041 91, Slovakia

Location

GSK Investigational Site

Poprad, 058 01, Slovakia

Location

GSK Investigational Site

Parktown, Gauteng, 2193, South Africa

Location

GSK Investigational Site

Capital Park, 0002, South Africa

Location

GSK Investigational Site

Overport, 4001, South Africa

Location

GSK Investigational Site

Parow, 7525, South Africa

Location

GSK Investigational Site

Port Elizabeth, 6001, South Africa

Location

GSK Investigational Site

Gyeonggi-do, 411-769, South Korea

Location

GSK Investigational Site

Seoul, 135-710, South Korea

Location

GSK Investigational Site

Alcorcón/Madrid, 28922, Spain

Location

GSK Investigational Site

Baracaldo/Vizcaya, 48903, Spain

Location

GSK Investigational Site

Cáceres, 10003, Spain

Location

GSK Investigational Site

Cuidad Real, 13002, Spain

Location

GSK Investigational Site

Jaén, 23007, Spain

Location

GSK Investigational Site

La Laguna (Santa Cruz de Tenerife), 38320, Spain

Location

GSK Investigational Site

Las Palmas de Gran Canaria, 35016, Spain

Location

GSK Investigational Site

Madrid, 28035, Spain

Location

GSK Investigational Site

Móstoles/Madrid, 28935, Spain

Location

GSK Investigational Site

Palma de Mallorca, 07014, Spain

Location

GSK Investigational Site

Pontevedra, 36071, Spain

Location

GSK Investigational Site

San Sebastián, 20014, Spain

Location

GSK Investigational Site

Santa Cruz de Tenerife, 38320, Spain

Location

GSK Investigational Site

Zaragoza, 50009, Spain

Location

GSK Investigational Site

Zaragoza, Spain

Location

GSK Investigational Site

Istanbul, 34865, Turkey (Türkiye)

Location

GSK Investigational Site

Istanbul, Turkey (Türkiye)

Location

Related Publications (3)

• 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.

  PMID: 22687601 BACKGROUND

• 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.

  PMID: 19620495 BACKGROUND

• 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.

  PMID: 20095796 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Paclitaxel; Lapatinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2004
• First Posted: January 9, 2004
• Study Start: January 1, 2004
• Primary Completion: October 1, 2006
• Study Completion: March 1, 2012
• Last Updated: May 6, 2015
• Results First Posted: March 31, 2014

Record last verified: 2014-02

Locations

PA (2); BR (2); CL (3); PL (6); DE (23); NL (5); AU (1); PE (2); US (45); NZ (2); RU (8); KR (2); ES (15); LA (4); CZ (3); BE (6); CA (6); TU (2); SL (4); AR (3); ZA (5); ME (4); IT (16); HU (4)