Breast CancerPhase 3NCT01966471
A Study of Trastuzumab Emtansine (Kadcyla) Plus Pertuzumab (Perjeta) Following Anthracyclines in Comparison With Trastuzumab (Herceptin) Plus Pertuzumab and a Taxane Following Anthracyclines as Adjuvant Therapy in Participants With Operable HER2-Positive Primary Breast Cancer
A Phase 3 study testing Trastuzumab Emtansine, Trastuzumab and Pertuzumab in people with Breast Cancer, run by Hoffmann-La Roche at 295 sites in 36 countries.
Trial summary
This two-arm, randomized, open-label, multicenter study will evaluate the efficacy and safety of trastuzumab emtansine in combination with pertuzumab versus trastuzumab in combination with pertuzumab and a taxane as adjuvant therapy in participants with human epidermal growth (HER) factor 2 (HER2)-positive primary… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Trastuzumab Emtansine, Trastuzumab and Pertuzumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,846 participants
- Where
- 295 sitesin 36 countries
- Study dates
- 31 Jan 2014to 4 Jun 2021
- 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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (</=) 1
- Non-metastatic histologically confirmed primary invasive breast carcinoma that was operable
- HER2-positive breast cancer
- Known hormone receptor status of the primary tumor
- Adequately excised: participants must have undergone either breast-conserving surgery or mastectomy/nipple- or skin-sparing mastectomy
- Pathological tumor-node-metastasis staging (Union for International Cancer Control-American Joint Committee on Cancer [UICC/AJCC] 7th edition): eligible participants must have either:
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- Node-positive disease (pN more than or equal to [>/=] 1), any tumor size except T0, and any hormonal receptor status; or Node-negative disease (pN0) with pathologic tumor size >2.0 centimeters by standard local assessment and negative for estrogen receptor (ER) and progesterone receptor (PR) determined by a central pathology laboratory
- Participants with synchronous bilateral invasive disease are eligible only if both lesions are HER2-positive
- No more than 9 weeks (63 days) may elapse between definitive breast surgery (or the last surgery if additional resection required for breast cancer) and randomization
- Baseline left ventricular ejection fraction (LVEF) >/=55% measured by echocardiogram (ECHO; preferred) or multiple-gated acquisition (MUGA) scans
- Documentation on hepatitis B virus (HBV) and hepatitis C virus (HCV) serology is required
- Female participants of childbearing potential must be willing to use one highly effective form of non-hormonal contraception or two effective forms of non-hormonal contraception. For male participants with partners of childbearing potential, one highly effective form of contraception or two effective forms of contraception must be used. Contraception must continue for the duration of study treatment and for 6 months after the last dose of study treatment
Who cannot join
- History of any prior (ipsilateral and/or contralateral) invasive breast carcinoma
- History of non-breast malignancies within the 5 years prior to randomization, except for carcinoma in situ (CIS) of the cervix, CIS of the colon, melanoma in situ, and basal cell and squamous cell carcinomas of the skin
- Any clinical T4 tumor as defined by tumor-node-metastasis classification in UICC/AJCC 7th edition, including inflammatory breast cancer
- For the currently diagnosed breast cancer, any previous systemic anti-cancer treatment (for example, neoadjuvant or adjuvant), including but not limited to, chemotherapy, anti-HER2 therapy (for example, trastuzumab, trastuzumab emtansine, pertuzumab, lapatinib, neratinib, or other tyrosine kinase inhibitors), hormonal therapy, OR anti-cancer radiation therapy (RT) (intra-operative radiotherapy as a boost at the time of primary surgery is acceptable)
- Previous therapy with anthracyclines, taxanes, or HER2-targeted therapy for any malignancy
- History of DCIS and/or lobular CIS (LCIS) that was treated with any form of systemic chemotherapy, hormonal therapy, or RT to the ipsilateral breast where invasive cancer subsequently developed. Participants who had their DCIS/LCIS treated with surgery only and/or contralateral DCIS treated with radiation are allowed to enter the study
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- Participants with contraindication to RT while adjuvant RT is clinically indicated
- Concurrent anti-cancer treatment in another investigational trial
- Cardiopulmonary dysfunction as defined by protocol: angina pectoris requiring anti-anginal medication, serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality, or clinically significant valvular disease, significant symptoms (Grade >/=2) relating to left ventricular dysfunction, cardiac arrhythmia, or cardiac ischemia, myocardial infarction within 12 months prior to randomization, uncontrolled hypertension, evidence of transmural infarction on electrocardiogram (ECG), requirement for oxygen therapy
- Other concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions/illness, uncontrolled infections, uncontrolled diabetes, or known infection with HIV
- Any known active liver disease. For participants who are known carriers of HBV/HCV, active hepatitis B/C infection must be ruled out per local guidelines
- Inadequate hematologic, renal or liver function
- Pregnant or lactating women
- Hypersensitivity to any of the study medications or any of the ingredients or excipients of these medications, including hypersensitivity to benzyl alcohol
- Chronic immunosuppressive therapies, including systemic corticosteroids
Trial locations and contacts
295 sites in 36 countries.
295 sites in 36 countries
United States50 sites
Anne Arundel Health System Research Instit-Annapolis Oncology Ctr
Annapolis, Maryland, 21401
University Cancer & Blood Center, LLC; Research
Athens, Georgia, 30607
Georgia Cancer Specialists
Atlanta, Georgia, 30341
Mercy Medical Center
Baltimore, Maryland, 21202
Dana Farber Cancer Inst.
Boston, Massachusetts, 02115
Beth Israel Deaconess Med Ctr
Boston, Massachusetts, 02215
Wellmont Medical Associates
Bristol, Virginia, 24201
Levine Cancer Institute
Charlotte, North Carolina, 28204
University of Virginia Health System; Hematology/Oncology Division
Charlottesville, Virginia, 22908
SCRI Tennessee Oncology Chattanooga
Chattanooga, Tennessee, 37404
Oncology Hematology Care Inc
Cincinnati, Ohio, 45242
Memorial Sloan-Kettering Cancer Center
Commack, New York, 11725
Karmanos Cancer Institute..
Detroit, Michigan, 48201
Henry Ford Hospital; Hematology Oncology
Detroit, Michigan, 48202
Duke University Medical Center
Durham, North Carolina, 27710
Holy Cross Hospital
Fort Lauderdale, Florida, 33308
Florida Cancer Specialists; SCRI
Fort Myers, Florida, 33901
The Center for Cancer and Blood Disorders - Fort Worth
Fort Worth, Texas, 76104
West Clinic
Germantown, Tennessee, 38138
Cone Health Cancer Center
Greensboro, North Carolina, 27403
Indiana University
Indianapolis, Indiana, 46202
Thompson Cancer Survival Center
Knoxville, Tennessee, 37916-2305
ProHEALTH Care Associates LLP
Lake Success, New York, 11042
Dartmouth Hitchcock Med Center
Lebanon, New Hampshire, 03756
Central Georgia Cancer Care PC
Macon, Georgia, 31201
Sarah Cannon Cancer Center - Tennessee Oncology, Pllc
Nashville, Tennessee, 37203
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08901
Kaiser Permanente - Oakland
Oakland, California, 94611
Mercy Clinic Oklahoma Communties, Inc
Oklahoma City, Oklahoma, 73120
Magee-Woman's Hospital
Pittsburgh, Pennsylvania, 15213
Quincy Medical Group; Canc Ctr at Blessing Hosp
Quincy, Illinois, 62301
Virginia Commonwealth University - Massey Cancer Center
Richmond, Virginia, 23298
Kaiser Permanente - Roseville; Oncology Pharmacy
Roseville, California, 95661
Kaiser Permanente - Sacramento; Oncology Pharmacy
Sacramento, California, 95814
UC Davis Cancer Center; Oncology
Sacramento, California, 95817
US oncology research at Minnesota Oncology
Saint Paul, Minnesota, 55102
Blue Ridge Cancer Care - Salem
Salem, Virginia, 24153
Southern California Kaiser Permanente
San Diego, California, 92108
Kaiser Permanente - San Jose
San Jose, California, 95119
Kaiser Permanente - San Leandro
San Leandro, California, 94577
HonorHealth Research Institute - Bisgrove
Scottsdale, Arizona, 85258
University of Washington
Seattle, Washington, 98195
Kaiser Permanente - South SF; Oncology Clinical trials
South San Francisco, California, 94080
Mercy Medical Research Institute
Springfield, Missouri, 65807
Florida Cancer Specialists; Saint Petersburg
St. Petersburg, Florida, 33719
Stanford University School of Medicine
Stanford, California, 94305-5151
Carle Cancer Center
Urbana, Illinois, 61801
Kaiser Permanente - Vallejo
Vallejo, California, 94589
Kaiser Permanente - Walnut Creek; Oncology Pharmacy
Walnut Creek, California, 94596
Cancer Center of Kansas
Wichita, Kansas, 67214-3728
Japan32 sites
Aichi Cancer Center Hospital, Breast Oncology
Aichi, 464-8681
Nagoya City University Hospital; Breast Surgery
Aichi, 467-8602
Natl Hosp Org Shikoku; Cancer Ctr, Surgery
Ehime, 791-0280
National Hospital Organization Kyushu Cancer Center;Breast Oncology
Fukuoka, 811-1395
Gunma University Hospital; Department of Breast and Endocrine Surgery
Gunma, 371-8511
Gunma Prefectural Cancer Center; Breast Oncology
Gunma, 373-8550
Hiroshima City Hiroshima Citizens Hospital; Breast Surgery
Hiroshima, 730-8518
Hiroshima University Hospital; Breast Surgery
Hiroshima, 734-8551
Hyogo College Of Medicine; Breast And Endocrine Surgery
Hyōgo, 663-8501
Sagara Hospital; Breast Surgery
Kagoshima, 892-0833
St. Marianna University School of Medicine Hospital, Breast and Endocrine Surgery
Kanagawa, 216-8511
Tokai University Hospital, Breast Surgery
Kanagawa, 259-1193
Kumamoto City Hospital, Breast and Endocrine Surgery
Kumamoto, 862-8505
Kumamoto Shinto General Hospital; Breast Cancer Center
Kumamoto, 862-8655
Kyoto University Hospital; Breast Surgery
Kyoto, 606-8507
Niigata Cancer Ctr Hospital; Breast Surgery
Niigata, 951-8566
Iwate Med Univ School of Med; Surgery
Numakunai, 028-3695
Kawasaki Medical School Hospital; Breast and Thyroid Surgery
Okayama, 701-0114
Naha-nishi Clinic; Surgery
Okinawa, 901-0154
National Hospital Organization Osaka National Hospital; Breast Surgery
Osaka, 540-0006
Osaka International Cancer Institute; Breast and Endocrine Surgery
Osaka, 541-8567
Saitama Medical University International Medical Center; Breast Oncology
Saitama, 350-1298
Saitama Cancer Center, Breast Oncology
Saitama, 362-0806
Shizuoka Cancer Center; Breast Surgery
Shizuoka, 411-8777
Shizuoka General Hospital; Breast Surgery
Shizuoka, 420-8527
Jichi Medical University; Breast Oncology
Tochigi, 329-0498
National Cancer Center Hospital; Medical Oncology
Tokyo, 104-0045
St. Luke's Internat. Hospital, Breast Surgical Oncology
Tokyo, 104-8560
Tokyo Metropolitan; Komagome Hospital, Surgery
Tokyo, 113-8677
The Cancer Inst. Hosp. of JFCR; Breast Oncology Center
Tokyo, 135-8550
Showa University Hospital; Breast Surgery
Tokyo, 142-8666
Tokyo Medical Uni. Hospital; Breast Oncology
Tokyo, 160-0023
France24 sites
Ico - Paul Papin
Angers, 49000
Clinique Sainte Catherine
Avignon, 84082
HOPITAL JEAN MINJOZ; Oncologie
Besançon, 25030
Institut Bergonie; Oncologie
Bordeaux, 33076
CHU de Brest - Hôpital de Morvan
Brest, 29609
Centre Francois Baclesse; Oncologie
Caen, 14076
Centre Jean Perrin; Oncologie
Clermont-Ferrand, 63011
Centre Georges Francois Leclerc; Oncologie 3
Dijon, 21079
Clinique Victor Hugo; Chimiotherapie
Le Mans, 72015
Centre Oscar Lambret; Cancerologie Gynecologique
Lille, 59020
Centre Leon Berard; Departement Oncologie Medicale
Lyon, 69373
Centre D'Oncologie de Gentilly; Oncology
Nancy, 54100
Centre Antoine Lacassagne
Nice, 06189
Institut de cancerologie du Gard
Nîmes, 30029
HOPITAL TENON; Cancerologie Medicale
Paris, 75970
Centre Armoricain de Radiotherapie, de Imagerie Medicale et de Oncologie (CARIO)
Plérin, 22190
Polyclinique De Courlancy; Centre Radiotherapie Oncologie
Reims, 51057
Centre Eugene Marquis; Service d'oncologie
Rennes, 35042
Ico Rene Gauducheau; Oncologie
Saint-Herblain, 44805
Institut De Cancerologie De La Loire; Consult Oncologie Niveau 0
Saint-Priest-en-Jarez, 42271
Institut d'oncologie de l'Orangerie; Chimiotherapie
Strasbourg, 67010
Centre Paul Strauss; Oncologie Medicale
Strasbourg, 67065
Institut Claudius Regaud; Departement Oncologie Medicale
Toulouse, 31059
Centre Alexis Vautrin; Oncologie Medicale
Vandœuvre-lès-Nancy, 54519
Germany24 sites
Klinikum Augsburg
Augsburg, 86156
Hochwaldkrankenhaus
Bad Nauheim, 61231
Frauenarzt-Zentrum Zehlendorf an der Teltower Eiche
Berlin, 14169
Gemeinschaftspraxis Dr. Bueckner und Dr. Nueckel
Bochum, 44787
Praxis Dr.med. Katja Ziegler-Löhr
Cologne, 50679
BAG Freiberg-Richter, Jacobasch, Illmer, Wolf; Gemeinschaftspraxis Hämatologie-Onkologie
Dresden, 01307
AGAPLESION Markus-Krankenhaus
Frankfurt, 60431
Städtische Kliniken Frankfurt am Main Höchst
Frankfurt, 65929
Praxis für Interdisziplinäre Onkologie und Hämatologie GbR
Freiburg im Breisgau, 79110
Dres.Jochen Wilke und Harald Wagner
Fürth, 90766
Niels-Stensen-Kliniken Franziskus-Hospital Harderberg GmbH
Georgsmarienhütte, 49124
Universitätsklinikum Hamburg-Eppendorf; Frauenklinik
Hamburg, 20246
Gynaekologisch-Onkologische Schwerpunktpraxis Prof. Dr. med. Lueck, Dr. Schrader und Dr. Noeding
Hanover, 30177
Medizinische Hochschule Hannover, Klinik für Frauenheilkunde und Geburtshilfe
Hanover, 30625
Klinikum Kulmbach; Frauenklinik
Kulmbach, 95326
Universitätsklinikum Schleswig-Holstein / Campus Lübeck; Klinik für Frauenheilkunde und Geburtshilfe
Lübeck, 23538
Klinikum Meiningen Klinik f.Gynäkologie und Geburtshilfe
Meiningen, 98617
Klinikum der Universität München; Campus Großhadern; Klinik und Poliklinik für Frauenheilkunde
München, 81377
Hämatologisch/Onkologische Praxis Prof. Dr. Decker, Studienzentrum
Ravensburg, 88212
Agaplesion Diakonieklinikum Rotenburg
Rotenburg (Wümme), 27356
Gynäkologie Kompetenzzentrum; Praxis Dr. med. Carsten Hielscher
Stralsund, 18439
Dres. Helmut Forstbauer, Carsten Ziske und Kollegen; Onkologische Schwerpunktpraxis
Troisdorf, 53840
GRN-Klinik Weinheim; Abt.Gynäkologie und Geburtshilfe
Weinheim, 69469
Klinikum Worms; Frauenklinik; Klinik für Gynäkologie und Geburtshilfe
Worms, 67550
United Kingdom22 sites
Velindre Cancer Centre; Oncology Dept
Cardiff, CF14 2TL
Cheltenham General Hospital; Gloucestershire Oncology Centre
Cheltenham, GL53 7AN
Royal Cornwall Hospital; Dept of Clinical Oncology
Cornwall, TR1 3LQ
University Hospital Coventry; InHANSE Unit and Clinical Trials Cancer Treatment Centre
Coventry, CV2 2DX
Western General Hospital; Edinburgh Breast Unit
Edinburgh, EH4 2XU
Royal Devon & Exeter Hospital; Oncology Centre
Exeter, EX2 5DW
Royal Surrey County Hospital; St. Lukes Cancer Centre
Guildford, GU2 7XX
Leicester Royal Infirmary; Dept. of Medical Oncology
Leicester, LE1 5WW
Royal Marsden Hospital - Fulham; Oncology Department
London, SW3 6JJ
Charing Cross Hospital
London, W6 8RF
Maidstone Hospital; Kent Oncology Centre
Maidstone, ME16 9QQ
Christie Hospital; Breast Cancer Research Office
Manchester, M20 4QL
Freeman Hospital; Northern Centre For Cancer Care
New Castle Upon Tyne, NE7 7DN
Mount Vernon Cancer Centre
Northwood, HA6 2RN
Nottingham City Hospital; Oncology
Nottingham, NG5 1PB
Peterborough City Hospital, Edith Cavell Campus; Oncology Department
Peterborough, PE3 9GZ
Queen Alexandra Hospital; Portsmouth Haematology & Oncology Centre, Level B
Portsmouth, PO6 3LY
Weston Park Hospital; Cancer Clinical Trials Centre
Sheffield, S10 2SJ
Musgrove Park Hospital; Department Clinical Research, Beacon Centre
Somerset, TA1 5DA
Uni Hospital of North Staffordshire; Staffordshire Oncology Centre
Stoke-on-Trent, ST4 6QG
Royal Marsden Hospital; Dept of Medical Oncology
Sutton, SM2 5PT
Yeovil District Hospital; Macmillan Cancer Unit
Yeovil, BA21 4AT
Canada18 sites
Tom Baker Cancer Centre-Calgary
Calgary, Alberta, T2N 4N2
Queen Elizabeth II Health Sciences Centre; Oncology
Halifax, Nova Scotia, B3H 2Y9
BC Cancer - Kelowna (Sindi Ahluwalia Hawkins Centre)
Kelowna, British Columbia, V1Y 5L3
Kingston General Hospital
Kingston, Ontario, K7L 2V7
Cite de La Sante de Laval; Hemato-Oncologie
Laval, Quebec, H7M 3L9
London Regional Cancer Centre
London, Ontario, N6A 4L6
Credit Valley Hospital/Carlo Fidani Peel Regional Cancer Centre
Mississauga, Ontario, L5M 2N1
Regional health authority A vitalite health network
Moncton, New Brunswick, E1C 8X3
McGill University; Glen Site; Oncology
Montreal, Quebec, H4A 3J1
Southlake Regional Health Center; Community Care Clinic / Oncology
Newmarket, Ontario, L3Y 2P9
Lions Gate Hospital
North Vancouver, British Columbia, V7L 2L7
Lakeridge Health Oshawa; Oncology
Oshawa, Ontario, L1G 2B9
Hopital du Saint Sacrement
Québec, Quebec, G1S 4L8
Sault Area Hospital
Sault Ste. Marie, Ontario, P6B 0A8
North York General Hospital
Toronto, Ontario, M2J 1V1
Princess Margaret Cancer Center
Toronto, Ontario, M5G 1Z5
BCCA-Vancouver Cancer Centre
Vancouver, British Columbia, V5Z 4E6
Windsor Regional Cancer Centre
Windsor, Ontario, N8W 2X3
Italy15 sites
Irccs Centro Di Riferimento Oncologico (CRO); Dipartimento Di Oncologia Medica
Aviano, Friuli Venezia Giulia, 33081
Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica
Bologna, Emilia-Romagna, 40138
Ospedale Antonio Perrino; Oncologia Medica
Brindisi, Apulia, 72100
ASST DI CREMONA; Unità di Patologia Mammaria Senologia e Breast Unit
Cremona, Lombardy, 26100
Ospedale San Raffaele
Milan, Lombardy, 20132
Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 1
Milan, Lombardy, 20133
Humanitas Centro Catanese Di Oncologia; Oncologia Medica
Misterbianco (CT), Sicily, 95045
ASST DI MONZA; Oncologia Medica
Monza, Lombardy, 20900
Istituto Nazionale Tumori Fondazione G. Pascale
Naples, Campania, 80131
IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II
Padova, Veneto, 35128
Ospedale Misericordia E Dolce; Oncologia Medica
Prato, Tuscany, 59100
Policlinico Universitario Campus Biomedico; Uoc Oncologia Medica
Rome, Lazio, 00128
Istituto Nazionale Tumori Regina Elena IRCCS
Rome, Lazio, 00144
Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia
Rozzano, Lombardy, 20089
Azienda Ospedaliera S. Maria - Terni; Oncologia
Terni, Umbria, 05100
Spain11 sites
Hospital del Mar; Servicio de Oncologia
Barcelona, 08003
Hospital Univ Vall d'Hebron; Servicio de Oncologia
Barcelona, 08035
Hospital Duran i Reynals; Oncologia
Barcelona, 08907
Hospital de Cruces; Servicio de Oncologia
Bilbao, Vizcaya, 48903
Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
Madrid, 28007
Centro Oncologico MD Anderson Internacional; Servicio de Oncologia
Madrid, 28033
Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia
Málaga, 29010
Hospital Universitario Virgen de Arrixaca; Servicio de Oncologia
Murcia, 30120
Hospital Universitario de Canarias;servicio de Oncologia
San Cristóbal de La Laguna, Tenerife, 38320
Hospital Clínico Universitario de Valencia; Servicio de Oncología
Valencia, 46010
Hospital Universitario Miguel Servet; Servicio Oncologia
Zaragoza, 50009
Australia8 sites
Burnside War Memorial Hospital, Clinical Trials Centre
Adelaide, South Australia, 5056
Chris O'Brien Lifehouse
Camperdown, New South Wales, 2050
Frankston Hospital; Oncology/Haematology
Frankston, Victoria, 3199
Austin Hospital; Medical Oncology
Heidelberg, Victoria, 3084
St John of God Murdoch Hospital; Oncology West
Murdoch, Western Australia, 6150
Epworth HealthCare; Clinical Trials Centre
Richmond, Victoria, 3121
Haematology & Oncology Clinics of Australia Research Centre
South Brisbane, Queensland, 4101
Calvary Mater Newcastle; Medical Oncology
Waratah, New South Wales, 2298
Brazil8 sites
Hospital de Cancer de Barretos
Barretos, São Paulo, 14784-400
Hospital Araujo Jorge; Departamento de Ginecologia E Mama
Goiânia, Goiás, 74605-070
Hospital Sao Lucas - PUCRS
Porto Alegre, Rio Grande do Sul, 90610-000
Hospital Nossa Senhora da Conceicao
Porto Alegre, Rio Grande do Sul, 91350-200
Instituto do Cancer do Estado de Sao Paulo - ICESP
São Paulo, São Paulo, 01246-000
Hospital Sirio Libanes; Centro de Oncologia
São Paulo, São Paulo, 01308-050
Hospital Perola Byington
São Paulo, São Paulo, 01317-000
Hospital Paulistano
São Paulo, São Paulo, 01321-000
Poland8 sites
Bialostockie Centrum Onkologii; Oddzial Onkologii Klinicznej
Bialystok, 15-027
Centrum Onkologii;Im. Franciszka Lukaszczyka;Onkologii
Bydgoszcz, 85-796
Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii
Gdansk, 80-214
Szpital Uniwersytecki w Krakowie, Oddział Kliniczny Kliniki Onkologii
Krakow, 30-688
Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii; Poradnia Chemioterapii
Lodz, 93-513
Centrum Onkologii Ziemi LUBELSKIEJ im. Sw Jana z Dukli, I oddz. Chemioterapii
Lublin, 20-090
Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina, Klinika Onkologii
Otwock, 05-400
Narodowy Inst.Onkologii im.Sklodowskiej-Curie Panstw.Inst.Bad; Klinika Nowtw.Piersi i Chir.Rekonstr
Warsaw, 02-781
Russia7 sites
Ivanovo Regional Oncology Dispensary
Ivanovo, 153040
Republican Clinical Oncologic Dispensary of Republic Of Tatarstan
Kazan', 420029
FSBI Russian Oncology Research Center n.a. Blokhin of MOH RF
Moscow, 115478
State Inst. Of Healthcare Orenburg Regional Clinical Oncology Dis
Orenburg, 460021
SBI for HPE "Ryazan State Medical University n.a. I.P. Pavlov" of MoH of RF
Ryazan, 390011
Scientific Research Institute n.a. N.N. Petrov
Saint Petersburg, 197758
SBI of Healthcare Samara Regional Clinical Oncology Dispensary
Samara, 443031
Taiwan6 sites
Changhua Christian Hospital; Dept of Surgery
Changhua, 500
Kaohsiung Medical Uni Chung-Ho Hospital; Dept of Surgery
Kaohsiung City, 807
Taichung Veterans General Hospital; Dept of Surgery
Taichung, 407
VETERANS GENERAL HOSPITAL; Department of General Surgery
Taipei, 00112
National Taiwan Uni Hospital; General Surgery
Taipei, 100
Tri-Service General Hospital, Division of General Surgery
Taipei, 114
South Korea5 sites
National Cancer Center; Medical Oncology
Gyeonggi-do, 410-769
Ajou Uni Hospital; Medical Oncology
Gyeonggi-do, 443-380
Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology
Seoul, 03080
Severance Hospital, Yonsei University Health System
Seoul, 03722
Samsung Medical Centre; Division of Hematology/Oncology
Seoul, 135-710
Czechia4 sites
Masarykuv onkologicky ustav
Brno, 656 53
Fakultni Nemocnice Hradec Kralove; Dept of Radiotherapy & Oncology
Hradec Králové, 500 05
MULTISCAN, s.r.o., Radiologicke centrum Pardubice
Pardubice, 532 03
Vseobecna fakultni nemocnice v Praze
Prague, 128 08
Hungary4 sites
Orszagos Onkologiai Intezet; B Belgyogyaszati Osztaly
Budapest, 1122
Municipal Hospital of Uzsoki Utca; Centre of Oncoradiology
Budapest, 1145
Debreceni Egyetem, Klinikai Kozpont, Onkologiai Klinika
Debrecen, 4032
Szegedi Tudomanyegyetem, AOK, Szent-Gyorgyi Albert Klinikai Kozpont, Onkoterapias Klinika
Szeged, 6720
Mexico4 sites
Instituto Nacional De Cancerologia; Oncology; Tumores Mamarios
Distrito Federal, 14000
Fundacion Rodolfo Padilla Padilla A.C.
León, 37000
Consultorio de Medicina Especializada; Dentro de Condominio San Francisco
Mexico City, 03100
Hospital San Jose Del Tec. de Monterrey; Oncology
Monterrey, 64020
Peru4 sites
Clinica de Especialidades Medicas
Lima, Lima 41
Clinica Internacional, Sede San Borja; Unidad de Investigacion de Clínica Internacional
Lima, Lima 41
Clinica San Borja
Lima, Lima 41
Instituto Oncologico Miraflore
Miraflores, Lima 18
Romania4 sites
Institutul Oncologic Prof. Dr. Al. Trestioreanu Bucuresti
Bucharest, 022328
Cluj Clinical County Hospital; Oncology Dept
Cluj-Napoca, 400006
Prof. Dr. I. Chiricuta Institute of Oncology
Cluj-Napoca, 400015
Regional Institute of Oncology Iasi
Iași, 700483
Thailand4 sites
Chulalongkorn Hospital; Medical Oncology
Bangkok, 10330
Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology
Bangkok, 10700
Chiang Rai Prachanukroh Hospital; Department Of Medicine
Chiang Rai, 57000
Buddhachinaraj Phitsanulok Hospital; Chemotherapy Unit ; Department of Medicine
Phitsanuok, 65000
Georgia3 sites
LTD Institute of Clinical Oncology
Tbilisi, 0159
Khechinashvili University Hospital ;Breast Unit
Tbilisi, 0177
Chemotherapy and Immunotherapy Clinic Medulla
Tbilisi, 0186
Hong Kong3 sites
Princess Margaret Hospital; Oncology
Hong Kong
Tuen Mun Hospital; Clinical Oncology
Hong Kong
Queen Mary Hospital; Dept of Surgery
Pokfulam
Sweden3 sites
Sahlgrenska Universitetssjukhuset; Jubileumskliniken
Gothenburg, 413 45
Universitetssjukhuset Örebro, Onkologiska kliniken
Örebro, 701 85
Akademiska sjukhuset, Onkologkliniken
Uppsala, 751 85
Switzerland3 sites
Kantonsspital Graubünden Medizin Onkologie; Onkologie und Hämatologie
Chur, 7000
Luzerner Kantonsspital; Medizinische Onkologie
Lucerne, 6004
Brust-Zentrum Zürich AG Seefeldstrasse 214 Zürich
Zurich, 8008
Belgium2 sites
UZ Leuven Gasthuisberg
Leuven, 3000
Sint Augustinus Wilrijk, Apotheek
Wilrijk, 2610
Bosnia and Herzegovina2 sites
University Clinical Center of the Republic of Srpska
Banja Luka, 78000
Clinic of Oncology, University Clinical Center Sarajevo
Sarajevo, 7100
Chile2 sites
Instituto Oncologico del sur
Temuco, 4810469
ONCOCENTRO APYS; Oncología
Viña del Mar, 2520598
Guatemala2 sites
Centro Oncológico Sixtino / Centro Oncológico SA
Guatemala City, 01010
Grupo Angeles
Guatemala City, 01015
Israel2 sites
Chaim Sheba Medical Center; Oncology Dept
Ramat Gan, 5262100
Sourasky / Ichilov Hospital; Oncology Department
Tel Aviv, 64239-06
Norway2 sites
Oslo universitetssykehus HF, Ullevål, Kreftsenteret
Oslo, 0450
Helse Stavanger HF, Stavanger Universitetssjukehus; Klinikk for Blod og kreftsykdommer
Stavanger, 4011
Philippines2 sites
San Juan de Dios Hospital;Oncology Unit
Pasay, 1300
East Avenue Medical Center
Quezon City, 1100
Singapore2 sites
National University Hospital; National University Cancer Institute, Singapore (NCIS)
Singapore, 119228
National Cancer Centre; Medical Oncology
Singapore, 169610
Ukraine2 sites
State Medical Academy; Oncology
Dnipropetrovsk, 43102
Lviv State Oncological Regional Treatment and Diagnostic Center
Lviv, 79031
About this study
Official title: A Randomized, Multicenter, Open-Label, Phase III Trial Comparing Trastuzumab Plus Pertuzumab Plus a Taxane Following Anthracyclines Versus Trastuzumab Emtansine Plus Pertuzumab Following Anthracyclines as Adjuvant Therapy in Patients With Operable HER2-Positive Primary Breast Cancer
This two-arm, randomized, open-label, multicenter study will evaluate the efficacy and safety of trastuzumab emtansine in combination with pertuzumab versus trastuzumab in combination with pertuzumab and a taxane as adjuvant therapy in participants with human epidermal growth (HER) factor 2 (HER2)-positive primary invasive breast cancer. Following surgery and anthracycline-based chemotherapy, participants will receive either trastuzumab emtansine at a dose of 3.6 milligrams per kilogram (mg/kg) and pertuzumab at a dose of 420 milligrams (mg) intravenously (IV) every 3 weeks (q3w) or trastuzumab at a dose of 6 mg/kg and pertuzumab at a dose of 420 mg IV q3w in combination with a taxane.
- Conditions
- Breast Cancer
- Being tested
- Trastuzumab Emtansine, Trastuzumab, Pertuzumab, Paclitaxel, Epirubicin
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trastuzumab EmtansineDrug
Also called Kadcyla
Trastuzumab emtansine IV infusion (duration 90 minutes) will be administered at 3.6 mg/kg q3w for up to 18 cycles (1 cycle = 21 days).
TrastuzumabDrug
Also called Herceptin
Trastuzumab IV infusion (duration 90 minutes) will be administered at 8 mg/kg loading dose followed by 6 mg/kg IV q3w for up to 18 cycles (1 cycle = 21 days).
PertuzumabDrug
Also called Perjeta
Pertuzumab infusion (duration 60 minutes) will be administered at 840 mg loading dose followed by 420 mg IV q3w for up to 18 cycles (1 cycle = 21 days).
PaclitaxelDrug
IV infusion of paclitaxel 80 mg/m^2 once weekly may be administered concurrently with trastuzumab in combination with pertuzumab for 12 weeks.
EpirubicinDrug
3 to 4 cycles (1 cycle = 21 days) of standard of care anthracycline-based chemotherapy using epirubicin may be administered in both Arms 1 and 2 as per discretion of the investigator and local prescribing information/institutional guidelines.
DoxorubicinDrug
3 to 4 cycles (1 cycle = 21 days) of standard of care anthracycline-based chemotherapy using doxorubicin may be administered in both Arms 1 and 2 as per discretion of the investigator and local prescribing information/institutional guidelines.
DocetaxelDrug
IV infusion either docetaxel every 3 weeks (q3w) (at 100 milligram per square meter [mg/m^2] for 3 cycles (1 cycle = 21 days); at 75 mg/m2 for 4 cycles; or start at 75 mg/m^2 in the first cycle and escalate to 100 mg/m^2 if no dose limiting toxicity occurs, for a total of 3 cycles at minimum) may be administered concurrently with trastuzumab in combination with pertuzumab.
CyclophosphamideDrug
3 to 4 cycles (1 cycle = 21 days) of standard of care anthracycline-based chemotherapy using cyclophosphamide (FEC) may be administered in both Arms 1 and 2 as per discretion of the investigator and local prescribing information/institutional guidelines.
5-FluorouracilDrug
3 to 4 cycles (1 cycle = 21 days) of standard of care anthracycline-based chemotherapy using 5-fluorouracil, may be administered in both Arms 1 and 2 as per discretion of the investigator and local prescribing information/institutional guidelines.
| Study group | Role | What they receive |
|---|---|---|
| Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane | Active comparator | Trastuzumab and pertuzumab will be administered concurrently for up to a total duration of 1 year (up to 18 cycles [1 Cycle = 21 days]) with the taxane (docetaxel or paclitaxel) component of chemotherapy following anthracycline [5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)] based chemotherapy. Receives: Drug: Trastuzumab; Drug: Pertuzumab; Drug: Paclitaxel; Drug: Epirubicin; Drug: Doxorubicin; Drug: Docetaxel; Drug: Cyclophosphamide; Drug: 5-Fluorouracil |
| Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab | Experimental | Trastuzumab emtansine and pertuzumab will continue for up to a total duration of 1 year (up to 18 cycles [1 Cycle = 21 days]) following anthracycline [5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)] based chemotherapy. Receives: Drug: Trastuzumab Emtansine; Drug: Epirubicin; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: 5-Fluorouracil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Invasive Disease-Free Survival (IDFS) in the Node-Positive Subpopulation
IDFS event was defined as the time from randomization until the date of first occurrence of one of the following: Ipsilateral invasive breast tumor recurrence (an invasive breast cancer [bc] involving the same breast parenchyma as the original primary lesion); Ipsilateral local-regional invasive bc recurrence (an invasive bc in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); Contralateral or ipsilateral second primary invasive bc; Distant recurrence (evidence of bc in any anatomic site [other than the three sites mentioned above]) that has either been histologically confirmed or clinically/radiographically diagnosed as recurrent invasive bc; Death attributable to any cause, including bc, non-bc, or unknown cause. 3-year IDFS event-free rate per randomized treatment arms in the ITT population was estimated using the Kaplan-Meier method and estimated the probability of a participant being event-free after 3 years after randomization.
Measured: Last participant randomized to data cut-off date of 27 November 2019 (approximately 70 months). The 3 year IDFS event-free rate was assessed based on the data collected for each participant considering the cut-off date mentioned above.
Invasive Disease-Free Survival (IDFS) in the Overall Population
IDFS event was defined as the time from randomization until the date of first occurrence of one of the following: Ipsilateral invasive breast tumor recurrence (an invasive breast cancer [bc] involving the same breast parenchyma as the original primary lesion); Ipsilateral local-regional invasive bc recurrence (an invasive bc in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); Contralateral or ipsilateral second primary invasive bc; Distant recurrence (evidence of bc in any anatomic site [other than the three sites mentioned above]) that has either been histologically confirmed or clinically/radiographically diagnosed as recurrent invasive bc; Death attributable to any cause, including bc, non-bc, or unknown cause. 3-year IDFS event-free rate per randomized treatment arms in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 3 years after randomization.
Measured: First participant randomized up to approximately 7.5 years
Secondary outcomes (9)
IDFS Plus Second Primary Non-Breast Cancer
IDFS including second primary non-breast cancer was defined the same way as IDFS for the primary endpoint but including second primary non breast invasive cancer as an event (with the exception of non-melanoma skin cancers and carcinoma in situ (CIS) of any site).
Measured: Baseline up to approximately 70 months
Disease-Free Survival (DFS)
DFS was defined as time between randomization and first occurrence of IDFS, second primary non-breast cancer and contralateral or ipsilateral ductal carcinoma in situ (DCIS).
Measured: Baseline up to approximately 70 months
Distant Recurrence-Free Interval (DRFI)
DRFI was defined as time between randomization and first occurrence of distant breast cancer recurrence.
Measured: Baseline up to approximately 70 months
Overall Survival (OS)
OS was defined as the time from randomization to death due to any cause.
Measured: First participant randomized up to approximately 7.5 years
Percentage of Participants With Adverse Events
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the national cancer institute common terminology criteria for AEs, Version 4.0 (NCI-CTCAE, v4.0).
Measured: From randomization to approximately 7.5 years
Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) From Baseline Over Time
LVEF was assessed using either echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scans.
Measured: First participant randomized up to approximately 7.5 years.
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score
The EORTC QLQ-C30 included global health status, functional scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea/vomiting, and pain) and single items (dyspnoea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Most questions used a 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale [1 'very poor' to 7 'Excellent']). Scores were averaged and transformed to 0 - 100 scale, whereby higher scores indicate greater functioning, greater quality of life, or a greater degree of symptoms, with changes of 7 - 15 points considered to be a clinically meaningful detioration to participants. A positive value means an increase, while a negative value means a decrease, in score at the indicated time-point relative to the score at baseline (Cycle 1, Day 1).
Measured: Baseline, Cycles 1, 2, 3, 4, 5, 9, 14, End of Treatment, Follow-up Month 6, Follow-up Month 12, Follow-up Month 18
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score
EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30. There are four functional scales (body image, sexual enjoyment, sexual functioning, future perspective [FP]) and four symptom scales (systemic side effects [SE], upset by hair loss, arm symptoms, breast symptoms). Questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores averaged and transformed to 0-100 scale. High score for functional scale indicated high/better level of functioning/healthy functioning. Higher scores for symptom scales represent higher levels of symptoms/problems. For functional scales, positive change from baseline indicated improvement in quality of life (QOL) while negative change from baseline indicated a deterioration. For symptom scales, positive change from baseline indicated deterioration and negative change indicated improvement.
Measured: Baseline, Cycles 1, 2, 3, 4, 5, 9, 14, End of Treatment, Follow-up Month 6, Follow-up Month 12, Follow-up Month 18
Time to Clinically Meaningful Deterioration in the Global Health Status/ Quality of Life and Functional (Physical, Role, and Cognitive) Subscales of the QLQ-C30 From First HER2-Targeted Treatment
The time to clinically meaningful deterioration in the global health status/Quality of life and Functional (Physical, Role, and Cognitive) subscales of the the QLQ-C30 was assessed from the time of the HER2-Targeted treatment to the worsening in the respective scales. Clinically meaningful deterioration is defined as a decrease in score of 10 points in Physical functioning and HRQoL; decrease of 7 points in Cognitive functioning, and decrease of 14 points in Role functioning.
Measured: From start of HER-2 targeted treatment up to 18 months after treatment discontinuation. The median time to clinically meaningful deterioration was assessed based on the data collection described above.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2013 (estimated)
- Study start31 Jan 2014
- Primary completion27 Nov 2019
- Study completion4 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 1,846 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01966471
- Sponsor's protocol ID
- BO28407
- Other IDs
- 2012-004902-82
- Status last verified
- Jun 2022
- First submitted
- 17 Oct 2013
- Last updated
- 14 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. doi: 10.1200/JCO.21.00896. Epub 2021 Dec 10.
PubMed 34890214
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Multicenter, Open-Label, Phase III Trial Comparing Trastuzumab Plus Pertuzumab Plus a Taxane Following Anthracyclines Versus Trastuzumab Emtansine Plus Pertuzumab Following Anthracyclines as Adjuvant Therapy in Patients With Operable HER2-Positive Primary Breast Cancer
- ClinicalTrials.gov ID
- NCT01966471
- Acronym / sponsor ID
- BO28407
- Conditions
- Breast Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,846 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 31 Jan 2014 (actual)
- Primary completion
- 27 Nov 2019 (actual)
- Study completion
- 4 Jun 2021 (actual)
- First posted
- 21 Oct 2013 (estimated)
- Results
- Posted 12 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This two-arm, randomized, open-label, multicenter study will evaluate the efficacy and safety of trastuzumab emtansine in combination with pertuzumab versus trastuzumab in combination with pertuzumab and a taxane as adjuvant therapy in participants with human epidermal growth (HER) factor 2 (HER2)-positive primary invasive breast cancer. Following surgery and anthracycline-based chemotherapy, participants will receive either trastuzumab emtansine at a dose of 3.6 milligrams per kilogram (mg/kg) and pertuzumab at a dose of 420 milligrams (mg) intravenously (IV) every 3 weeks (q3w) or trastuzumab at a dose of 6 mg/kg and pertuzumab at a dose of 420 mg IV q3w in combination with a taxane.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane | Active comparator | Drug: Trastuzumab, Drug: Pertuzumab, Drug: Paclitaxel, Drug: Epirubicin, Drug: Doxorubicin, Drug: Docetaxel, Drug: Cyclophosphamide, Drug: 5-FluorouracilTrastuzumab and pertuzumab will be administered concurrently for up to a total duration of 1 year (up to 18 cycles [1 Cycle = 21 days]) with the taxane (docetaxel or paclitaxel) component of chemotherapy following anthracycline [5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)] based chemotherapy. |
| Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab | Experimental | Drug: Trastuzumab Emtansine, Drug: Epirubicin, Drug: Doxorubicin, Drug: Cyclophosphamide, Drug: 5-FluorouracilTrastuzumab emtansine and pertuzumab will continue for up to a total duration of 1 year (up to 18 cycles [1 Cycle = 21 days]) following anthracycline [5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)] based chemotherapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (</=) 1
- Non-metastatic histologically confirmed primary invasive breast carcinoma that was operable
- HER2-positive breast cancer
- Known hormone receptor status of the primary tumor
- Adequately excised: participants must have undergone either breast-conserving surgery or mastectomy/nipple- or skin-sparing mastectomy
Key exclusion criteria (15 listed)
- History of any prior (ipsilateral and/or contralateral) invasive breast carcinoma
- History of non-breast malignancies within the 5 years prior to randomization, except for carcinoma in situ (CIS) of the cervix, CIS of the colon, melanoma in situ, and basal cell and squamous cell carcinomas of the skin
- Any clinical T4 tumor as defined by tumor-node-metastasis classification in UICC/AJCC 7th edition, including inflammatory breast cancer
- For the currently diagnosed breast cancer, any previous systemic anti-cancer treatment (for example, neoadjuvant or adjuvant), including but not limited to, chemotherapy, anti-HER2 therapy (for example, trastuzumab, trastuzumab emtansine, pertuzumab, lapatinib, neratinib, or other tyrosine kinase inhibitors), hormonal therapy, OR anti-cancer radiation therapy (RT) (intra-operative radiotherapy as a boost at the time of primary surgery is acceptable)
- Previous therapy with anthracyclines, taxanes, or HER2-targeted therapy for any malignancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Trastuzumab EmtansineAlso: KadcylaTrastuzumab emtansine IV infusion (duration 90 minutes) will be administered at 3.6 mg/kg q3w for up to 18 cycles (1 cycle = 21 days). | Drug | Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab |
| TrastuzumabAlso: HerceptinTrastuzumab IV infusion (duration 90 minutes) will be administered at 8 mg/kg loading dose followed by 6 mg/kg IV q3w for up to 18 cycles (1 cycle = 21 days). | Drug | Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane |
| PertuzumabAlso: PerjetaPertuzumab infusion (duration 60 minutes) will be administered at 840 mg loading dose followed by 420 mg IV q3w for up to 18 cycles (1 cycle = 21 days). | Drug | Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane |
| PaclitaxelIV infusion of paclitaxel 80 mg/m^2 once weekly may be administered concurrently with trastuzumab in combination with pertuzumab for 12 weeks. | Drug | Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane |
| Epirubicin3 to 4 cycles (1 cycle = 21 days) of standard of care anthracycline-based chemotherapy using epirubicin may be administered in both Arms 1 and 2 as per discretion of the investigator and local prescribing information/institutional guidelines. | Drug | Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab, Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane |
| Doxorubicin3 to 4 cycles (1 cycle = 21 days) of standard of care anthracycline-based chemotherapy using doxorubicin may be administered in both Arms 1 and 2 as per discretion of the investigator and local prescribing information/institutional guidelines. | Drug | Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab, Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane |
| DocetaxelIV infusion either docetaxel every 3 weeks (q3w) (at 100 milligram per square meter [mg/m^2] for 3 cycles (1 cycle = 21 days); at 75 mg/m2 for 4 cycles; or start at 75 mg/m^2 in the first cycle and escalate to 100 mg/m^2 if no dose limiting toxicity occurs, for a total of 3 cycles at minimum) may be administered concurrently with trastuzumab in combination with pertuzumab. | Drug | Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane |
| Cyclophosphamide3 to 4 cycles (1 cycle = 21 days) of standard of care anthracycline-based chemotherapy using cyclophosphamide (FEC) may be administered in both Arms 1 and 2 as per discretion of the investigator and local prescribing information/institutional guidelines. | Drug | Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab, Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane |
| 5-Fluorouracil3 to 4 cycles (1 cycle = 21 days) of standard of care anthracycline-based chemotherapy using 5-fluorouracil, may be administered in both Arms 1 and 2 as per discretion of the investigator and local prescribing information/institutional guidelines. | Drug | Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab, Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane |
Primary outcome
Invasive Disease-Free Survival (IDFS) in the Node-Positive Subpopulation
Time frame: Last participant randomized to data cut-off date of 27 November 2019 (approximately 70 months). The 3 year IDFS event-free rate was assessed based on the data collected for each participant considering the cut-off date mentioned above.
IDFS event was defined as the time from randomization until the date of first occurrence of one of the following: Ipsilateral invasive breast tumor recurrence (an invasive breast cancer [bc] involving the same breast parenchyma as the original primary lesion); Ipsilateral local-regional invasive bc recurrence (an invasive bc in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); Contralateral or ipsilateral second primary invasive bc; Distant recurrence (evidence of bc in any anatomic site [other than the three sites mentioned above]) that has either been histologically confirmed or clinically/radiographically diagnosed as recurrent invasive bc; Death attributable to any cause, including bc, non-bc, or unknown cause. 3-year IDFS event-free rate per randomized treatment arms in the ITT population was estimated using the Kaplan-Meier method and estimated the probability of a participant being event-free after 3 years after randomization.
Invasive Disease-Free Survival (IDFS) in the Overall Population
Time frame: First participant randomized up to approximately 7.5 years
IDFS event was defined as the time from randomization until the date of first occurrence of one of the following: Ipsilateral invasive breast tumor recurrence (an invasive breast cancer [bc] involving the same breast parenchyma as the original primary lesion); Ipsilateral local-regional invasive bc recurrence (an invasive bc in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); Contralateral or ipsilateral second primary invasive bc; Distant recurrence (evidence of bc in any anatomic site [other than the three sites mentioned above]) that has either been histologically confirmed or clinically/radiographically diagnosed as recurrent invasive bc; Death attributable to any cause, including bc, non-bc, or unknown cause. 3-year IDFS event-free rate per randomized treatment arms in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 3 years after randomization.
9 secondary outcomes
IDFS Plus Second Primary Non-Breast Cancer
Time frame: Baseline up to approximately 70 months
Disease-Free Survival (DFS)
Time frame: Baseline up to approximately 70 months
Distant Recurrence-Free Interval (DRFI)
Time frame: Baseline up to approximately 70 months
Overall Survival (OS)
Time frame: First participant randomized up to approximately 7.5 years
Percentage of Participants With Adverse Events
Time frame: From randomization to approximately 7.5 years
Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) From Baseline Over Time
Time frame: First participant randomized up to approximately 7.5 years.
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score
Time frame: Baseline, Cycles 1, 2, 3, 4, 5, 9, 14, End of Treatment, Follow-up Month 6, Follow-up Month 12, Follow-up Month 18
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score
Time frame: Baseline, Cycles 1, 2, 3, 4, 5, 9, 14, End of Treatment, Follow-up Month 6, Follow-up Month 12, Follow-up Month 18
Time to Clinically Meaningful Deterioration in the Global Health Status/ Quality of Life and Functional (Physical, Role, and Cognitive) Subscales of the QLQ-C30 From First HER2-Targeted Treatment
Time frame: From start of HER-2 targeted treatment up to 18 months after treatment discontinuation. The median time to clinically meaningful deterioration was assessed based on the data collection described above.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34890214Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. doi: 10.1200/JCO.21.00896. Epub 2021 Dec 10.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
295 sites in 36 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Trastuzumab Emtansine, Trastuzumab and Pertuzumab in people with Breast Cancer, run by Hoffmann-La Roche at 295 sites in 36 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 12 inclusion and 15 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 14 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 295 sites in United States, Japan, France, Germany, United Kingdom and 31 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 12 Jan 2021). 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?
Invasive Disease-Free Survival (IDFS) in the Node-Positive Subpopulation (time frame: Last participant randomized to data cut-off date of 27 November 2019 (approximately 70 months). The 3 year IDFS event-free rate was assessed based on the data collected for each participant considering the cut-off date mentioned above.). The study lists 2 primary outcomes in all. 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 NCT01966471, which also lists 1 linked publication.
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 14 Jun 2022.