AzTrials
AzTrials

Breast CancerPhase 3NCT00667251

Chemotherapy and Lapatinib or Trastuzumab in Treating Women With HER2/Neu-Positive Metastatic Breast Cancer

A Phase 3 study testing trastuzumab, docetaxel and lapatinib ditosylate in people with Breast Cancer, run by Novartis Pharmaceuticals at 257 sites in 21 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This was a multi-center, multinational, randomized, open-label, Phase III study comparing combination taxane-based chemotherapy plus lapatinib to combination taxane-based chemotherapy plus trastuzumab in women with documented evidence of human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
trastuzumab, docetaxel and lapatinib ditosylate
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
652 participants
Where
257 sitesin 21 countries
Study dates
7 Oct 2008to 27 Jul 2022
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed adenocarcinoma of the breast.
  • MBC (stage IV) at primary diagnosis or at relapse after curative intent therapy.
  • Local or central laboratory confirmed HER2/neu overexpressing and/or amplified disease in the invasive component of the primary or metastatic lesion as defined by:
  • 3+ over expression by immunohistochemistry (IHC) (>30% of invasive tumour cells);
  • 2+ or 3+ (in 30% or less neoplastic cells) overexpression by IHC analysis AND fluorescence or chromogenic in situ hybridization (FISH/CISH) test demonstrating HER2/neu gene amplification;
  • HER2/neu gene amplification by FISH/CISH [>6 HER2/neu gene copies per nucleus, or a FISH/CISH ratio (HER2 gene copies to chromosome 17 signals) of >=2.2]
Show all 10Show fewer
  • Subjects must have had evidence of metastatic disease, but measurable disease was not mandatory. To be considered evaluable for overall response rate (CR and PR), subjects must have had at least 1 measurable lesion as follows:
  • X-ray, physical exam >=20 mm.
  • Conventional computed tomography (CT) scan, magnetic resonance imaging (MRI) >=20 mm.
  • Spiral CT scan >=10 mm.

Who cannot join

  • Subjects with a history of other malignancies, except: adequately treated ductal carcinoma in-situ or lobular carcinoma in-situ, adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumor (non-breast) curatively treated with no evidence of disease for >=5 years.
  • Subjects who had received prior chemotherapy, immunotherapy, biologic therapy or HER2/neu targeted therapy for recurrent or MBC.
  • Subjects receiving ongoing anti-cancer treatment or other investigational anti-cancer agents for breast cancer or subjects who had used an investigational drug within 30 days or 5 half-lives (if known), whichever was longer, preceding the date of randomization.
  • Subjects with: CNS metastases (including leptomeningeal involvement), serious cardiac illness, peripheral neuropathy grade 2 or greater, subjects with gastrointestinal tract disease, subjects receiving CYP3A4 inhibitors or inducers, and subjects with history of allergic or hypersensitivity reactions to any study drug or their excipients.

Trial locations and contacts

257 sites in 21 countries.

257 sites in 21 countries

United States53 sites

  • Novartis Investigative Site

    Anchorage, Alaska, 99508

  • Novartis Investigative Site

    Augusta, Georgia, 30901

  • Novartis Investigative Site

    Bellevue, Washington, 98004

  • Novartis Investigative Site

    Berkeley, California, 94704

  • Novartis Investigative Site

    Bozeman, Montana, 59715

  • Novartis Investigative Site

    Canton, Ohio, 44718

  • Novartis Investigative Site

    Chesapeake, Virginia, 23320

  • Novartis Investigative Site

    Chicago, Illinois, 60657

  • Novartis Investigative Site

    Colorado Springs, Colorado, 80907

  • Novartis Investigative Site

    Columbia, South Carolina, 29210

  • Novartis Investigative Site

    Cooperstown, New York, 13326

  • Novartis Investigative Site

    Denver, Colorado, 80204

  • Novartis Investigative Site

    Denville, New Jersey, 07834

  • Novartis Investigative Site

    Evansville, Indiana, 47713

  • Novartis Investigative Site

    Goshen, Indiana, 46526

  • Novartis Investigative Site

    Grand Island, Nebraska, 68803

  • Novartis Investigative Site

    Greensboro, North Carolina, 27403

  • Novartis Investigative Site

    Greenwich, Connecticut, 06830

  • Novartis Investigative Site

    Highland, California, 92346

  • Novartis Investigative Site

    Hot Springs, Arkansas, 71913

  • Novartis Investigative Site

    Indianapolis, Indiana, 46237

  • Novartis Investigative Site

    Kearney, Nebraska, 68845

  • Novartis Investigative Site

    Kearney, Nebraska, 68847

  • Novartis Investigative Site

    Kirkland, Washington, 98034

  • Novartis Investigative Site

    Kissimmee, Florida, 34741

  • Novartis Investigative Site

    Lawrenceville, Georgia, 30046

  • Novartis Investigative Site

    Loxahatchee Groves, Florida, 33470

  • Novartis Investigative Site

    Memphis, Tennessee, 38120

  • Novartis Investigative Site

    Milwaukee, Wisconsin, 53226

  • Novartis Investigative Site

    Montebello, California, 90640

  • Novartis Investigative Site

    Mount Vernon, Washington, 98273

  • Novartis Investigative Site

    Munster, Indiana, 46321

  • Novartis Investigative Site

    New Albany, Indiana, 47150

  • Novartis Investigative Site

    New Port Richey, Florida, 34655

  • Novartis Investigative Site

    Oak Lawn, Illinois, 60453

  • Novartis Investigative Site

    Parsippany, New Jersey, 07054

  • Novartis Investigative Site

    Pittsburgh, Pennsylvania, 15212-4772

  • Novartis Investigative Site

    Portland, Oregon, 97227

  • Novartis Investigative Site

    Post Falls, Idaho, 83854

  • Novartis Investigative Site

    Salem, Virginia, 24153

  • Novartis Investigative Site

    Savannah, Georgia, 31405

  • Novartis Investigative Site

    Seattle, Washington, 98109

  • Novartis Investigative Site

    Sequim, Washington, 98382

  • Novartis Investigative Site

    Southington, Connecticut, 06489

  • Novartis Investigative Site

    Stamford, Connecticut, 06902-3628

  • Novartis Investigative Site

    Tacoma, Washington, 98405

  • Novartis Investigative Site

    Towson, Maryland, 21204

  • Novartis Investigative Site

    Trumbull, Connecticut, 06611

  • Novartis Investigative Site

    Tucson, Arizona, 85715

  • Novartis Investigative Site

    Waterbury, Connecticut, 06708

  • Novartis Investigative Site

    Wenatchee, Washington, 98801

  • Novartis Investigative Site

    Wheaton, Maryland, 20902

  • Novartis Investigative Site

    Wooster, Ohio, 44691

Other trials in United States

Germany35 sites

  • Novartis Investigative Site

    Berlin, 10117

  • Novartis Investigative Site

    Berlin, 10367

  • Novartis Investigative Site

    Bielefeld, North Rhine-Westphalia, 33611

  • Novartis Investigative Site

    Bonn, North Rhine-Westphalia, 53113

  • Novartis Investigative Site

    Brandenburg, 14770

  • Novartis Investigative Site

    Coburg, Bavaria, 96450

  • Novartis Investigative Site

    Coesfeld, North Rhine-Westphalia, 48653

  • Novartis Investigative Site

    Cologne, North Rhine-Westphalia, 51067

  • Novartis Investigative Site

    Dresden, Saxony, 01127

  • Novartis Investigative Site

    Eggenfelden, Bavaria, 84307

  • Novartis Investigative Site

    Essen, North Rhine-Westphalia, 45122

  • Novartis Investigative Site

    Frankfurt am Main, Hesse, 60596

  • Novartis Investigative Site

    Fulda, Hesse, 36043

  • Novartis Investigative Site

    Fürstenwalde, Brandenburg, 15517

  • Novartis Investigative Site

    Fürth, Bavaria, 90766

  • Novartis Investigative Site

    Goslar, Lower Saxony, 38642

  • Novartis Investigative Site

    Halle, Saxony-Anhalt, 06120

  • Novartis Investigative Site

    Hamburg, 20095

  • Novartis Investigative Site

    Hamburg, 22081

  • Novartis Investigative Site

    Hamburg, 22767

  • Novartis Investigative Site

    Hanover, Lower Saxony, 30559

  • Novartis Investigative Site

    Heidelberg, Baden-Wurttemberg, 69115

  • Novartis Investigative Site

    Koblenz, Rhineland-Palatinate, 56068

  • Novartis Investigative Site

    Leer, Lower Saxony, 26789

  • Novartis Investigative Site

    Lich, Hesse, 35423

  • Novartis Investigative Site

    Lübeck, Schleswig-Holstein, 23538

  • Novartis Investigative Site

    Porta Westfalica, North Rhine-Westphalia, 32457

  • Novartis Investigative Site

    Regensburg, Bavaria, 93049

  • Novartis Investigative Site

    Rosenheim, Bavaria, 83022

  • Novartis Investigative Site

    Saarbrücken, Saarland, 66113

  • Novartis Investigative Site

    Stuttgart, Baden-Wurttemberg, 70190

  • Novartis Investigative Site

    Troisdorf, North Rhine-Westphalia, 53840

  • Novartis Investigative Site

    Velbert, North Rhine-Westphalia, 42551

  • Novartis Investigative Site

    Weiden, Bavaria, 92637

  • Novartis Investigative Site

    Witten, North Rhine-Westphalia, 58452

Other trials in Germany

Canada25 sites

  • Novartis Investigative Site

    Barrie, Ontario, L4M 6M2

  • Novartis Investigative Site

    Charlottetown, Prince Edward Island, C1A 8T5

  • Novartis Investigative Site

    Edmonton, Alberta, T6G 1Z2

  • Novartis Investigative Site

    Greater Sudbury, Ontario, P3E 5J1

  • Novartis Investigative Site

    Hamilton, Ontario, L8V 5C2

  • Novartis Investigative Site

    Kelowna, British Columbia, V1Y 5L3

  • Novartis Investigative Site

    Kingston, Ontario, K7L 5P9

  • Novartis Investigative Site

    London, Ontario, N6A 4L6

  • Novartis Investigative Site

    Moncton, New Brunswick, E1C 6Z8

  • Novartis Investigative Site

    Montreal, Quebec, H1T 2M4

  • Novartis Investigative Site

    Montreal, Quebec, H2L 4M1

  • Novartis Investigative Site

    Montreal, Quebec, H2W 1S6

  • Novartis Investigative Site

    Newmarket, Ontario, L3Y 2P9

  • Novartis Investigative Site

    Ottawa, Ontario, K1H 8L6

  • Novartis Investigative Site

    Québec, Quebec, G1S 4L8

  • Novartis Investigative Site

    Regina, Saskatchewan, S4T 7T1

  • Novartis Investigative Site

    Saint John, New Brunswick, E2L 4L2

  • Novartis Investigative Site

    Saskatoon, Saskatchewan, S7N 4H4

  • Novartis Investigative Site

    Sault Ste. Marie, Ontario, P6B 0A8

  • Novartis Investigative Site

    St. Catharines, Ontario, L2R 7C6

  • Novartis Investigative Site

    Surrey, British Columbia, V3V 1Z2

  • Novartis Investigative Site

    Thunder Bay, Ontario, P7B 6V4

  • Novartis Investigative Site

    Vancouver, British Columbia, V5Z 4E6

  • Novartis Investigative Site

    Victoria, British Columbia, V8R 6V5

  • Novartis Investigative Site

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

United Kingdom22 sites

  • Novartis Investigative Site

    Bournemouth, BH7 7DW

  • Novartis Investigative Site

    Brighton, BN2 5BE

  • Novartis Investigative Site

    Chelmsford, CM1 7ET

  • Novartis Investigative Site

    Cheltenham, GL53 7AN

  • Novartis Investigative Site

    Colchester, CO3 3NB

  • Novartis Investigative Site

    Cottingham, Hull, HU16 5JQ

  • Novartis Investigative Site

    Derby, DE22 3NE

  • Novartis Investigative Site

    Edmonton, N18 1QX

  • Novartis Investigative Site

    Guildford, GU2 7XX

  • Novartis Investigative Site

    Harrogate, HG2 7SX

  • Novartis Investigative Site

    Huddersfield, HD3 3EA

  • Novartis Investigative Site

    London, SW3 6JJ

  • Novartis Investigative Site

    Newcastle upon Tyne, NE7 7DN

  • Novartis Investigative Site

    Norwich, NR4 7UY

  • Novartis Investigative Site

    Nottingham, NG5 1PB

  • Novartis Investigative Site

    Oxford, OX3 7LJ

  • Novartis Investigative Site

    Poole, Dorset, BH15 2JB

  • Novartis Investigative Site

    Sheffield, S10 2SJ

  • Novartis Investigative Site

    Shrewsbury, SY3 8XQ

  • Novartis Investigative Site

    Sutton, SM2 5PT

  • Novartis Investigative Site

    Whitchurch, Cardiff, CF14 2TL

  • Novartis Investigative Site

    York, YO31 8HE

Other trials in United Kingdom

Spain16 sites

  • Novartis Investigative Site

    A Coruña, 15009

  • Novartis Investigative Site

    Alcorcón, 28922

  • Novartis Investigative Site

    Alicante, 03010

  • Novartis Investigative Site

    Badalona, 08916

  • Novartis Investigative Site

    Barcelona, 08036

  • Novartis Investigative Site

    Elche, 03202

  • Novartis Investigative Site

    Girona, 17007

  • Novartis Investigative Site

    Jaén, 23007

  • Novartis Investigative Site

    Lugo, 27003

  • Novartis Investigative Site

    Madrid, 28007

  • Novartis Investigative Site

    Madrid, 28034

  • Novartis Investigative Site

    Madrid, 28040

  • Novartis Investigative Site

    Majadahonda (Madrid), 28222

  • Novartis Investigative Site

    Pozuelo de Alarcon (Madrid), 28223

  • Novartis Investigative Site

    Seville, 41013

  • Novartis Investigative Site

    Valencia, 46009

Other trials in Spain

Australia13 sites

  • Novartis Investigative Site

    Adelaide, South Australia, 5000

  • Novartis Investigative Site

    Bedford Park, South Australia, 5042

  • Novartis Investigative Site

    Box Hill, Victoria, 3128

  • Novartis Investigative Site

    Fitzroy, Victoria, 3065

  • Novartis Investigative Site

    Garran, Australian Capital Territory, 2606

  • Novartis Investigative Site

    Hobart, Tasmania, 7000

  • Novartis Investigative Site

    Kurralta Park, South Australia, 5037

  • Novartis Investigative Site

    Liverpool, New South Wales, 2170

  • Novartis Investigative Site

    North Sydney, New South Wales, 2060

  • Novartis Investigative Site

    Subiaco, Western Australia, 6008

  • Novartis Investigative Site

    Tweed Heads, New South Wales, 2485

  • Novartis Investigative Site

    Wodonga, Victoria, 3690

  • Novartis Investigative Site

    Woolloongabba, Queensland, 4102

Other trials in Australia

Japan12 sites

  • Novartis Investigative Site

    Aichi, 464-8681

  • Novartis Investigative Site

    Chiba, 277-8577

  • Novartis Investigative Site

    Ehime, 791-0280

  • Novartis Investigative Site

    Kagoshima, 892-0833

  • Novartis Investigative Site

    Kanagawa, 241-8515

  • Novartis Investigative Site

    Osaka, 540-0006

  • Novartis Investigative Site

    Osaka, 565-0871

  • Novartis Investigative Site

    Saitama, 350-1298

  • Novartis Investigative Site

    Saitama, 362-0806

  • Novartis Investigative Site

    Shizuoka, 411-8777

  • Novartis Investigative Site

    Tokyo, 104-8560

  • Novartis Investigative Site

    Tokyo, 113-8677

Other trials in Japan

Russia11 sites

  • Novartis Investigative Site

    Arkhangelsk, 163045

  • Novartis Investigative Site

    Ivanovo, 153013

  • Novartis Investigative Site

    Kazan', 420029

  • Novartis Investigative Site

    Kirov, 610021

  • Novartis Investigative Site

    Lipetsk, 398005

  • Novartis Investigative Site

    Moscow, 115 478

  • Novartis Investigative Site

    Ryazan, 390011

  • Novartis Investigative Site

    Saint Petersburg, 197022

  • Novartis Investigative Site

    Saint Petersburg, 197758

  • Novartis Investigative Site

    Stavropol, 355047

  • Novartis Investigative Site

    Ufa, 450054

Other trials in Russia

Argentina9 sites

  • Novartis Investigative Site

    Capital Federal, Buenos Aires, C1405CUB

  • Novartis Investigative Site

    Capital Federal, Buenos Aires, C1426ANZ

  • Novartis Investigative Site

    Cipolletti, Río Negro Province, R8324EMB

  • Novartis Investigative Site

    Ciudad Autonoma de Buenos Aires, Buenos Aires, C1280AEB

  • Novartis Investigative Site

    La Plata, Buenos Aires, B1920CMK

  • Novartis Investigative Site

    Rosario, Santa Fe Province, S2000KZE

  • Novartis Investigative Site

    San Miguel de Tucumán, 4000

  • Novartis Investigative Site

    Santa Fe, 3000

  • Novartis Investigative Site

    Viedma, Río Negro Province, R8500ACE

Other trials in Argentina

France9 sites

  • Novartis Investigative Site

    Angers, 49033

  • Novartis Investigative Site

    Bordeaux, 33075

  • Novartis Investigative Site

    Bordeaux, 33077

  • Novartis Investigative Site

    Caen, 14076

  • Novartis Investigative Site

    Marseille, 13273

  • Novartis Investigative Site

    Metz-Tessy, 74370

  • Novartis Investigative Site

    Nantes, 44202

  • Novartis Investigative Site

    Paris, 75014

  • Novartis Investigative Site

    Strasbourg, 67085

Other trials in France

Italy8 sites

  • Novartis Investigative Site

    Aviano (PN), Friuli Venezia Giulia, 33081

  • Novartis Investigative Site

    Chieti, 66100

  • Novartis Investigative Site

    Genoa, Liguria, 16132

  • Novartis Investigative Site

    Lecce, Apulia, 73100

  • Novartis Investigative Site

    Prato (PO), Tuscany, 59100

  • Novartis Investigative Site

    Rome, Lazio, 00189

  • Novartis Investigative Site

    Sassari, Sardinia, 07100

  • Novartis Investigative Site

    Sora (FR), Lazio, 03039

Other trials in Italy

Poland8 sites

  • Novartis Investigative Site

    Gdansk, 80-219

  • Novartis Investigative Site

    Lodz, 93-509

  • Novartis Investigative Site

    Olsztyn, 10-226

  • Novartis Investigative Site

    Olsztyn, 10-513

  • Novartis Investigative Site

    Płock, 09-400

  • Novartis Investigative Site

    Rzeszów, 35-021

  • Novartis Investigative Site

    Warsaw, 02-781

  • Novartis Investigative Site

    Warsaw, 04-125

Other trials in Poland

South Korea6 sites

  • Novartis Investigative Site

    Gyeonggi-do, 10408

  • Novartis Investigative Site

    Gyeonggi-do, 410-769

  • Novartis Investigative Site

    Seoul, 03722

  • Novartis Investigative Site

    Seoul, 110-744

  • Novartis Investigative Site

    Seoul, 120-752

  • Novartis Investigative Site

    Songpa-gu, Seoul, 138-736

Other trials in South Korea

Israel5 sites

  • Novartis Investigative Site

    Beersheba, 84101

  • Novartis Investigative Site

    Holon, 58100

  • Novartis Investigative Site

    Petah Tikva, 49100

  • Novartis Investigative Site

    Poria – Neve Oved, 15208

  • Novartis Investigative Site

    Ramat Gan, 52621

Other trials in Israel

Taiwan5 sites

  • Novartis Investigative Site

    Changhua, 500

  • Novartis Investigative Site

    Taichung, 404

  • Novartis Investigative Site

    Tainan County, 736

  • Novartis Investigative Site

    Taipei, 100

  • Novartis Investigative Site

    Taipei, 112

Other trials in Taiwan

Belgium4 sites

  • Novartis Investigative Site

    Ghent, 9000

  • Novartis Investigative Site

    Jette, 1090

  • Novartis Investigative Site

    Liège, 4000

  • Novartis Investigative Site

    Namur, 5000

Other trials in Belgium

Netherlands4 sites

  • Novartis Investigative Site

    Amsterdam, 1091 AC

  • Novartis Investigative Site

    Delft, 2625 AD

  • Novartis Investigative Site

    Dordrecht, 3318 AT

  • Novartis Investigative Site

    Maastricht, 6229 HX

Other trials in Netherlands

Ukraine4 sites

  • Novartis Investigative Site

    Dnipro, 49102

  • Novartis Investigative Site

    Dnipropetrovsk, 49100

  • Novartis Investigative Site

    Lviv, 79031

  • Novartis Investigative Site

    Sumy, 40005

Other trials in Ukraine

India3 sites

  • Novartis Investigative Site

    Bangalore, 560038

  • Novartis Investigative Site

    Nagpur, 440010

  • Novartis Investigative Site

    Pune, 411001

Other trials in India

Mexico3 sites

  • Novartis Investigative Site

    Ciudad Obregón, Sonora, 85000

  • Novartis Investigative Site

    Cuernavaca, Morelos, 62450

  • Novartis Investigative Site

    Mexico City, CP 14080

Other trials in Mexico

Thailand2 sites

  • Novartis Investigative Site

    Bangkok, 10700

  • Novartis Investigative Site

    Chiang Mai, 50200

Other trials in Thailand

About this study

Official title: A Randomized, Open-Label, Phase III Study of Taxane Based Chemotherapy With Lapatinib or Trastuzumab as First-Line Therapy for Women With HER2/Neu Positive Metastatic Breast Cancer

This was a multi-center, multinational, randomized, open-label, Phase III study comparing combination taxane-based chemotherapy plus lapatinib to combination taxane-based chemotherapy plus trastuzumab in women with documented evidence of human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer (MBC) (by local or central laboratory testing) who had received no prior chemotherapy or HER2 targeted therapy in the metastatic setting.

Read the detailed description

Subjects were stratified by

  • Prior (neo) adjuvant HER2/neu targeted therapy (yes, no)
  • Prior (neo) adjuvant taxane chemotherapy (yes, no)
  • Planned taxane treatment (once weekly paclitaxel versus docetaxel once every 3 weeks)
  • Liver metastasis (yes, no)

Subjects were randomized 1:1 to the following treatments to a planned sample size of approximately 600 subjects (to achieve 536 centrally confirmed HER2 positive subjects):

  • Taxane based chemotherapy plus lapatinib for 24 weeks followed by single agent lapatinib
  • Taxane based chemotherapy plus trastuzumab for 24 weeks followed by single agent trastuzumab

The choice of taxane (once weekly paclitaxel versus docetaxel once every 3 weeks) was at the discretion of the treating physician and was specified at the time of subject randomization.

A protocol-specified interim analysis was conducted on 27-Apr-2012, following which the participants in the Lapatinib plus taxane based chemotherapy arm could cross over to Taxane based chemotherapy plus Trastuzumab.

Conditions
Breast Cancer
Being tested
trastuzumab, docetaxel, lapatinib ditosylate, paclitaxel
Keywords
recurrent breast cancer, HER2-positive breast cancer, stage IV breast cancer
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • trastuzumabBiological

    IV q weekly (loading dose 4mg/kg; subsequent doses 2mg/kg) or IV q 3 weekly (loading dose 8mg/kg, subsequent doses 6mg/kg).

  • docetaxelDrug

    75mg/m2 IV q 3 weekly, day 1 of a 3 week cycle for 8 cycles plus G-CSF (when given together with lapatinib).

  • lapatinib ditosylateDrug

    1250 mg once daily (while given with taxane). 1500mg once daily (when given alone after taxane completion).

  • paclitaxelDrug

    80mg/m2 IV q weekly days 1, 8 and 15 of a 4-week cycle for 6 cycles.

Study groups in NCT00667251
Study groupRoleWhat they receive
LapatinibActive comparatorPlus taxane based chemotherapy
Receives: Drug: docetaxel; Drug: lapatinib ditosylate; Drug: paclitaxel
TrastuzumabActive comparatorPlus taxane based chemotherapy.
Receives: Biological: trastuzumab; Drug: docetaxel; Drug: paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival (PFS) at the Time of Primary Results

    Progression-free survival (PFS) is the time from randomization to the earliest date of RECIST 1.0 assessment of disease progression (with radiological evidence), death from any cause, or censoring. Disease progression was assessed by the Investigator and defined by RECIST v1.0 as a 20% increase in the sum of the longest diameter of target lesions, a measurable increase in a non-target lesion, or the appearance of new lesions.

    Measured: From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up to approximately 39 months

Secondary outcomes (25)

  1. Progression Free Survival (PFS) at the Time of Final Analysis

    Progression-free survival (PFS) is the time from randomization to the earliest date of RECIST 1.0 assessment of disease progression (with radiological evidence), death from any cause, or censoring. Disease progression was assessed by the Investigator and defined by RECIST v1.0 as a 20% increase in the sum of the longest diameter of target lesions, a measurable increase in a non-target lesion, or the appearance of new lesions. Subjects who crossover the treatment to Trastuzumab (TTax/T) after interim analysis, were censored at the last PFS assessment before crossover.

    Measured: From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up to approximately 45 months

  2. Overall Survival (OS) (IIT Population)

    Overall Survival (OS) was defined as the time interval between the date of randomization and the date of death from any cause. Subjects who were still alive at the time of the final analysis or became lost to follow-up, were censored at their last contact date. Subjects who crossover the treatment to Trastuzumab (TTax/T) after interim analysis, were censored at last known alive date prior to crossover.

    Measured: From date of randomization until date of death from any cause, assessed up approximately 165 months

  3. Overall Survival (OS) (Central HER2+ Population)

    Overall Survival (OS) was defined as the time interval between the date of randomization and the date of death from any cause. Subjects who were still alive at the time of the final analysis or became lost to follow-up, were censored at their last contact date. Subjects who crossover the treatment to Trastuzumab (TTax/T) after interim analysis, were censored at last known alive date prior to crossover.

    Measured: From date of randomization until date of death from any cause, assessed up approximately 165 months

  4. Incidence of Central Nervous System (CNS) Metastasis at First Progression (IIT Population)

    The incidence of Central Nervous System (CNS) metastasis at first progression was defined as the ratio of the number of subjects with CNS metastasis at progression over the total number of subjects.

    Measured: From date of randomization to CNS metastases at time of first progression, assessed up approximately 45 months

  5. Incidence of Central Nervous System (CNS) Metastasis at First Progression (Central HER2+ Population)

    The incidence of Central Nervous System (CNS) metastasis at first progression was defined as the ratio of the number of subjects with CNS metastasis at progression over the total number of subjects.

    Measured: From date of randomization to CNS metastases at time of first progression, assessed up approximately 45 months

  6. Time to Central Nervous System (CNS) Metastasis (IIT Population)

    Time to Central Nervous System (CNS) metastasis was defined as the time from randomization until disease progression where CNS metastasis was documented at the time of first breast cancer progression. Subjects who crossed over the treatment to Trastuzumab (TTax/T) after interim analysis, were censored at RECIST assessment prior to crossover.

    Measured: From date of randomization to CNS metastases at time of first progression, assessed up approximately 45 months

  7. Time to Central Nervous System (CNS) Metastasis (Central HER2+ Population)

    Time to Central Nervous System (CNS) metastasis was defined as the time from randomization until disease progression where CNS metastasis was documented at the time of first breast cancer progression. Subjects who crossed over the treatment to Trastuzumab (TTax/T) after interim analysis, were censored at RECIST assessment prior to crossover.

    Measured: From date of randomization to CNS metastases at time of first progression, assessed up approximately 45 months

  8. Overall Response Rate (ORR) (IIT Population)

    Overall Response Rate (ORR) was defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR). The ORR was calculated from the Investigator's assessment of response based on RECIST 1.1. Subjects with an unknown or missing response were treated as non-responders; i.e., they were included in the denominator when calculating the percentages.

    Per Response Evaluation Criteria In Solid Tumors (RECIST v1.1) for target lesions and assessed by MRI:

    • Complete Response (CR): Disappearance of all target and non-target lesions.
    • Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as a reference the Baseline sum LD.
    • Overall Response (OR): CR + PR.

    Measured: From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up approximately 45 months

  9. Overall Response Rate (ORR) (Central HER2+ Population)

    Overall Response Rate (ORR) was defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR). The ORR was calculated from the Investigator's assessment of response based on RECIST 1.1. Subjects with an unknown or missing response were treated as non-responders; i.e., they were included in the denominator when calculating the percentages.

    Per Response Evaluation Criteria In Solid Tumors (RECIST v1.1) for target lesions and assessed by MRI:

    • Complete Response (CR): Disappearance of all target and non-target lesions.
    • Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as a reference the Baseline sum LD.
    • Overall Response (OR): CR + PR.

    Measured: From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up approximately 45 months

  10. Clinical Benefit Response (CBR) (IIT Population)

    Clinical Benefit Response (CBR) was defined as the percentage with evidence of Complete Response (CR), Partial Response (PR) (participants with at least 1 measurable lesion at baseline), or maintaining Stable Disease (SD) for at least 24 weeks (all subjects, with or without measurable disease at baseline) while on study, according to the investigator assessment of response per RECIST 1.1 criteria. Participants were considered to be positive (Yes) for CBR if they experienced any CR or PR for any duration prior to progressive disease. Participants were considered to be negative (No) for CBR if they had progressive disease prior to Week 24 without prior confirmed CR or PR.

    Measured: From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up approximately 45 months

  11. Clinical Benefit Response (CBR) (Central HER2+ Population)

    Clinical Benefit Response (CBR) was defined as the percentage with evidence of Complete Response (CR), Partial Response (PR) (participants with at least 1 measurable lesion at baseline), or maintaining Stable Disease (SD) for at least 24 weeks (all subjects, with or without measurable disease at baseline) while on study, according to the investigator assessment of response per RECIST 1.1 criteria. Participants were considered to be positive (Yes) for CBR if they experienced any CR or PR for any duration prior to progressive disease. Participants were considered to be negative (No) for CBR if they had progressive disease prior to Week 24 without prior confirmed CR or PR.

    Measured: From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up approximately 45 months

  12. Time to Response (TTR) (IIT Population)

    Time to Response was defined as the time from randomization to the earliest date of Complete Response (CR) or Partial Response (PR). The event of first response was the first CR or PR; censoring was at PD date for those who progressed or at the last RECIST date if no progression occurred.

    Measured: From date of randomization until date of first response, assessed up approximately 45 months

  13. Time to Response (TTR) (Central HER2+ Population)

    Time to Response was defined as the time from randomization to the earliest date of Complete Response (CR) or Partial Response (PR). The event of first response was the first CR or PR; censoring was at PD date for those who progressed or at the last RECIST date if no progression occurred.

    Measured: From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up approximately 45 months

  14. Duration of Response (DoR) (IIT Population)

    Duration of Response (DOR) was defined as the duration between the date of first documented Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) and the date of first documented sign of Progressive Disease or Death, with censoring at the last RECIST date if no progression occurred.

    Measured: From first documented evidence of CR or PR (the response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up approximately 165 months

  15. Duration of Response (DoR) (Central HER2+ Population)

    Duration of Response (DOR) was defined as the duration between the date of first documented Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) and the date of first documented sign of Progressive Disease or Death, with censoring at the last RECIST date if no progression occurred.

    Measured: From first documented evidence of CR or PR (the response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up approximately 165 months

  16. EORTC QLQ-C30 Global Score at 12 Weeks

    The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQC-30) is a questionnaire developed to assess the quality of life of cancer patients. The global score ranges from 0-100, with higher values representing a better quality of life.

    Measured: Week 12

  17. Number of Participants Achieving European Quality of Life (EuroQol) - 5 Domain (EQ-5D) Score (Canadian and Australian Centers Only)

    The European Quality of Life (EuroQol) - 5 Domain (EQ-5D) self-administered questionnaire consists of two pages comprising the EQ-5D descriptive system and the EQ Visual Analogue Scale (VAS). The EQ-5D descriptive system comprises five dimensions of health (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and each dimension comprises three levels (no problems, some problems, extreme problems, unable to perform the activity).

    Measured: Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 96, Week 120, Week 144

  18. Change From Baseline in the EQ-VAS Score (Canadian and Australian Centers Only)

    The European Quality of Life (EuroQol) - 5 Domain (EQ-5D) self-administered questionnaire consists of two pages comprising the EQ-5D descriptive system and the EQ Visual Analogue Scale (VAS). The EQ VAS records the patient's self-rated health on a vertical visual analogue 0-100 scale, where the endpoints are labelled 'The best health you can imagine' (100) and 'The worst health you can imagine' (0).

    Measured: Baseline, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 96, Week 120, Week 144

  19. Number of Participants With Healthcare Utilization (Canadian and Australian Centers Only)

    The measures of healthcare resource utilization collected were categorized: hospitalization/inpatient visit, Institutionalized, Outpatient visit.

    Measured: From date of randomization till 28 days safety follow-up, assessed up to 40 months

  20. Number of Participant Hospitalized (Canadian and Australian Centers Only)

    The number of hospitalizations were categorized: >0 and =<2, >2 and =<4 and >4.

    Measured: From date of randomization till 28 days safety follow-up, assessed up to 40 months

  21. Total and Average Duration of Hospitalization (Canadian and Australian Centers Only)

    The total duration of hospitalization in days and average duration of each hospitalization in days were summarized using descriptive statistics.

    Measured: From date of randomization till 28 days safety follow-up, assessed up to 40 months

  22. Reasons for Hospitalization (Canadian and Australian Centers Only)

    The reasons for hospitalization were categorized: Breast Cancer, Febrile Neutropenia, Infection, Other and Pneumonia.

    Measured: From date of randomization till 28 days safety follow-up, assessed up to 40 months

  23. Type of Ward (Hospital Unit) (Canadian and Australian Centers Only)

    The type of ward (hospital unit) were categorized: general ward, intensive care unit, oncology ward, rehabilitation unit and other.

    Measured: From date of randomization till 28 days safety follow-up, assessed up to 40 months

  24. Discharge Destinations (Canadian and Australian Centers Only)

    The discharge destinations were categorized: died, home, rehabilitation facility and transfer to other hospital.

    Measured: From date of randomization till 28 days safety follow-up, assessed up to 40 months

  25. Estrogen Receptor (ER) and Progesterone Receptor (PgR) Status

    Immunohistochemistry (IHC) analysis of estrogen receptor (ER) and progesterone receptor (PgR) were performed as part of the mandatory central laboratory testing for protocol-specified biomarkers.

    Measured: Up to approximately 39 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Apr 2008 (estimated)
  2. Study start7 Oct 2008
  3. Primary completion1 Aug 2012
  4. Study completion27 Jul 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
652 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00667251
Sponsor's protocol ID
108919
Other IDs
CLAP016A2303, CAN-NCIC-MA31, 2007-004568-27, CDR0000594764, EGF108919
Status last verified
Mar 2025
First submitted
25 Apr 2008
Last updated
21 Mar 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Publications

  • Gelmon KA, Boyle FM, Kaufman B, Huntsman DG, Manikhas A, Di Leo A, Martin M, Schwartzberg LS, Lemieux J, Aparicio S, Shepherd LE, Dent S, Ellard SL, Tonkin K, Pritchard KI, Whelan TJ, Nomikos D, Nusch A, Coleman RE, Mukai H, Tjulandin S, Khasanov R, Rizel S, Connor AP, Santillana SL, Chapman JA, Parulekar WR. Lapatinib or Trastuzumab Plus Taxane Therapy for Human Epidermal Growth Factor Receptor 2-Positive Advanced Breast Cancer: Final Results of NCIC CTG MA.31. J Clin Oncol. 2015 May 10;33(14):1574-83. doi: 10.1200/JCO.2014.56.9590. Epub 2015 Mar 16.

    PubMed 25779558

  • Ho D, Huang J, Chapman JW, Leitzel K, Ali SM, Shepherd L, Parulekar WR, Ellis CE, Crescnzo RJ, Zhu L, Virk S, Nomikos D, Aparicio S, Gelmon KA, Carney WP, Lipton A. Impact of serum HER2, TIMP-1, and CAIX on outcome for HER2+ metastatic breast cancer patients: CCTG MA.31 (lapatinib vs. trastuzumab). Breast Cancer Res Treat. 2017 Aug;164(3):571-580. doi: 10.1007/s10549-017-4273-x. Epub 2017 May 8.

    PubMed 28484925

  • Liu S, Chen B, Burugu S, Leung S, Gao D, Virk S, Kos Z, Parulekar WR, Shepherd L, Gelmon KA, Nielsen TO. Role of Cytotoxic Tumor-Infiltrating Lymphocytes in Predicting Outcomes in Metastatic HER2-Positive Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial. JAMA Oncol. 2017 Nov 9;3(11):e172085. doi: 10.1001/jamaoncol.2017.2085. Epub 2017 Nov 9.

    PubMed 28750133

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing trastuzumab, docetaxel and lapatinib ditosylate in people with Breast Cancer, run by Novartis Pharmaceuticals at 257 sites in 21 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 257 sites in United States, Germany, Canada, United Kingdom, Spain and 16 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Jun 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS) at the Time of Primary Results (time frame: From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up to approximately 39 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00667251, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2025.

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