A Study of Pertuzumab in Addition to Chemotherapy and Trastuzumab as Adjuvant Therapy in Participants With Human Epidermal Growth Receptor 2 (HER2)-Positive Primary Breast Cancer

Breast Cancer Clinical Trial

— APHINITY  

Official title:

A Randomized Multicenter, Double-Blind, Placebo-Controlled Comparison of Chemotherapy Plus Trastuzumab Plus Placebo Versus Chemotherapy Plus Trastuzumab Plus Pertuzumab as Adjuvant Therapy in Patients With Operable HER2-Positive Primary Breast Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01358877
• Other study ID #: BO25126
• Secondary ID: TOC4939G2010-022
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 8, 2011
• Est. completion date: November 28, 2024

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized, double-blind, placebo-controlled, two-arm study will assess the safety and efficacy of pertuzumab in addition to chemotherapy plus trastuzumab as adjuvant therapy in participants with operable HER2-positive primary breast cancer. This study will be carried out in collaboration with the Breast International Group (BIG).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 4804
• Est. completion date: November 28, 2024
• Est. primary completion date: December 19, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Non-metastatic operable primary invasive HER2-positive carcinoma of the breast that is histologically confirmed, and adequately excised

• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (</=) 1

• Known hormone receptor status (estrogen receptor and progesterone receptor)

• The interval between definitive surgery for breast cancer and the first dose of chemotherapy must be no more than 8 weeks (56 days). The first cycle of chemotherapy must be administered within 7 days of randomization or on Day 56, whichever occurs first

• Baseline left ventricular ejection fraction (LVEF) greater than or equal to (>/=) 55 percent (%) measured by echocardiogram (ECHO) or Multiple-Gated Acquisition (MUGA) Scan

• Confirmed HER2 positive status

• Completion of all necessary baseline laboratory and radiologic investigations prior to randomization

• Women of childbearing potential and male participants with partners of childbearing potential must agree to use effective contraception (as defined by the protocol) by the participant and/or partner for the duration of the study treatment and for at least 7 months after the last dose of study drug

Exclusion Criteria:

• History of any prior (ipsi- and/or contralateral) invasive breast cancer

• History of non-breast malignancies within the 5 years prior to study entry, except for carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous cell carcinomas of the skin

• Any "clinical" T4 tumor as defined by primary tumor/regional lymph nodes/distant metastasis (TNM), including inflammatory breast cancer

• Any node-negative tumor

• Any previous systemic chemotherapy for cancer or radiotherapy for cancer

• Prior use of anti-HER2 therapy for any reason or other prior biologic or immunotherapy for cancer

• Concurrent anti-cancer treatment in another investigational trial

• Serious cardiac or cardiovascular disease or condition

• Other concurrent serious diseases that may interfere with planned treatment including severe pulmonary conditions/illness

• Abnormal laboratory tests immediately prior to randomization

• Pregnant or lactating women

• Sensitivity to any of the study medications or any of the ingredients or excipients of these medications

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• 5-Fluorouracil
5-Fluorouracil will be administered as per the schedule specified in the respective arm.
• Carboplatin
Carboplatin will be administered as per the schedule specified in the respective arm.
• Cyclophosphamide
Cyclophosphamide will be administered as per the schedule specified in the respective arm.
• Docetaxel
Docetaxel will be administered as per the schedule specified in the respective arm.
• Doxorubicin
Doxorubicin will be administered as per the schedule specified in the respective arm.
• Epirubicin
Epirubicin will be administered as per the schedule specified in the respective arm.
• Paclitaxel
Paclitaxel will be administered as per the schedule specified in the respective arm.
• Pertuzumab
Pertuzumab will be administered as per the schedule specified in the respective arm.
• Placebo
Placebo will be administered as per the schedule specified in the respective arm.
• Trastuzumab
Trastuzumab will be administered as per the schedule specified in the respective arm.

Locations

Country	Name	City	State
Argentina	Centro Medico San Roque	San Miguel de Tucuman
Argentina	Isis Centro Especializado de Luces; Oncology	Santa Fe
Australia	Royal Adelaide Hospital; Oncology	Adelaide	South Australia
Australia	Wesley Medical Centre; Clinic For Haematology and Oncology	Auchenflower	Queensland
Australia	Mater Hospital; Oncology	Brisbane	Queensland
Australia	Monash Medical Centre; Oncology	Clayton	Victoria
Australia	Geelong Hospital; Andrew Love Cancer Centre	Geelong	Victoria
Australia	Austin Hospital; Medical Oncology	Heidelberg	Victoria
Australia	Royal Hobart Hospital; Medical Oncology	Hobart	Tasmania
Australia	Lismore Base Hospital; Cancer Care & Haematology Unit	Lismore	New South Wales
Australia	Peter Maccallum Cancer Institute; Medical Oncology	Melbourne	Victoria
Australia	Sir Charles Gairdner Hospital; Medical Oncology	Perth	Western Australia
Australia	Mater Misericordiae Hospital; Chemotherapy Cottage	Sydney	New South Wales
Australia	Newcastle Mater Misericordiae Hospital; Oncology	Waratah	New South Wales
Australia	Westmead Hospital; Medical Oncology and Pallative Care	Westmead	New South Wales
Austria	Lkh-Univ. Klinikum Graz; Klinik Für Innere Medizin I	Graz
Austria	Tiroler Landeskrankenanstalten Ges.M.B.H.; Abt. Für Gynäkologie	Innsbruck
Austria	Ordensklinikum Linz Barmherzige Schwestern; Abt. fur Innere Medizin 1	Linz
Austria	Lhk Feldkirch; Interne Medizin Abt.	Rankweil
Austria	Lkh Salzburg - Univ. Klinikum Salzburg; Iii. Medizinische Abt.	Salzburg
Austria	A. Ö. Krankenhaus Der Barmherzigen Brüder; Interne Abt.	St Veit An Der Glan
Austria	Lkh Vöcklabruck; I. Abt. Für Innere Medizin	Vöcklabruck
Austria	Klinikum Kreuzschwestern Wels; Iii. Interne Abt.	Wels
Austria	Krankenhaus Der Stadt Wien-Hietzing; Abt. Für Gynäkologie U. Geburtshilfe	Wien
Austria	Medizinische Universität Wien; Univ.Klinik für Frauenheilkunde - Klinik für Gynäkologie	Wien
Austria	Medizinische Universität Wien; Univ.Klinik für Innere Medizin I - Abt. für Onkologie	Wien
Belgium	Institut Jules Bordet	Anderlecht
Belgium	GHdC Site Notre Dame	Charleroi
Belgium	UZ Antwerpen	Edegem
Belgium	Jessa Zkh (Campus Virga Jesse)	Hasselt
Belgium	AZ Groeninge	Kortrijk
Belgium	UZ Leuven Gasthuisberg	Leuven
Belgium	CHU Sart-Tilman	Liège
Belgium	Clinique Ste-Elisabeth	Namur
Belgium	Sint Augustinus Wilrijk	Wilrijk
Bulgaria	SHATO - Sofia	Sofia
Bulgaria	UMHAT Tsaritsa Yoanna - ISUL; Clinic of Oncotherapy	Sofia
Bulgaria	SHATOD Dr. Marko Antonov Markov-Varna, EOOD	Varna
Canada	Tom Baker Cancer Centre; Dept of Medicine	Calgary	Alberta
Canada	Cross Can Inst	Edmonton	Alberta
Canada	Queen Elizabeth II Health Sciences Centre; Oncology	Halifax	Nova Scotia
Canada	Hamilton Health Sciences - Juravinski Cancer Centre	Hamilton	Ontario
Canada	BC Cancer Agency, CSI	Kelowna	British Columbia
Canada	Cancer Centre of Southeastern Ontario; Kingston General Hospital	Kingston	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	Credit Valley Hospital/Carlo Fidani Peel Regional Cancer Centre	Mississauga	Ontario
Canada	Chum Hopital Notre Dame; Centre D'Oncologie	Montreal	Quebec
Canada	Hopital Maisonneuve- Rosemont; Oncology	Montreal	Quebec
Canada	Hopital Sacre-Coeur Research Centre	Montreal	Quebec
Canada	Southlake Regional Health Center	Newmarket	Ontario
Canada	Ottawa Regional Cancer Centre	Ottawa	Ontario
Canada	Hopital du Saint Sacrement	Quebec City	Quebec
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Atlantic Health Science Corporation; Saint John Regional Hospital Facility	Saint John	New Brunswick
Canada	Niagara Health Systems - St. Catherines General Site; Niagara Health System-St. Catharines Site	St. Catharines	Ontario
Canada	Northeastern Ontario; Regional Cancer Centre	Sudbury	Ontario
Canada	BC Cancer ? Surrey	Surrey	British Columbia
Canada	Mount Sinai Hospital	Toronto	Ontario
Canada	Princess Margaret Cancer Center	Toronto	Ontario
Canada	Sunnybrook Odette Cancer Centre	Toronto	Ontario
Canada	BCCA-Vancouver Cancer Centre	Vancouver	British Columbia
Canada	Bcca - Vancouver Island Cancer Centre; Oncology	Victoria	British Columbia
Canada	CancerCare Manitoba; Neuro-Oncology	Winnipeg	Manitoba
Chile	INTOP	Providencia
Chile	Fundacion Arturo Lopez Perez	Santiago
China	Cancer Hospital Chinese Academy of Medical Sciences.	Beijing
China	The Affiliated Hospital of Military Medical Sciences(The 307th Hospital of Chinese PLA)	Beijing
China	Jilin Cancer Hospital	Changchun
China	the First Hospital of Jilin University	Changchun
China	Hu Nan Provincial Cancer Hospital	Changsha
China	Sichuan Provincial People's Hospital	Chengdu
China	The 900th Hospital of PLA joint service support force	Fuzhou
China	Fujian Medical University Union Hospital	Fuzhou City
China	Guangdong General Hospital	Guangzhou
China	Sun Yet-sen University Cancer Center	Guangzhou City
China	The First Affiliated Hospital of College of Medicine, Zhejiang University	Hangzhou
China	Harbin Medical University Cancer Hospital	Harbin
China	The 1st Affiliated Hospital of Nanchang Unversity	Nanchang
China	Changhai Hospital of Shanghai	Shanghai
China	Shanghai First People's Hospital	Shanghai
China	Shanghai Jiao Tong University School of Medicine (SJTUSM) - Ruijin Hospital (GuangCi Hospital)	Shanghai
China	Fudan University Shanghai Cancer Center	Shanghai City
China	Hebei Medical University Fourth Hospital;(Tumor Hospital of Hebei Province)	Shijiazhuang
China	Hubei Cancer Hospital	Wuhan
China	Tongji Hosp, Tongji Med. Col, Huazhong Univ. of Sci. & Tech	Wuhan
China	Xiehe Hospital, Tongji Medical College Huazhong University of Science & Technology	Wuhan
Colombia	Fundacion Cardioinfantil	Bogota
Colombia	Inst. Nacional de Cancerologia; Clinica de Seno	Bogota
Colombia	Hospital Pablo Tobon Uribe	Medellin
Colombia	Oncomedica S.A.	Monteria
Croatia	Uni Hospital Split; Oncology & Radiotherapy	Split
Croatia	General Hospital Varazdin	Varazdin
Croatia	Clinical Hospital Centre Zagreb	Zagreb
Czechia	Masarykuv onkologicky ustav	Brno
Czechia	Fakultni Nemocnice Hradec Kralove; Dept of Radiotherapy & Oncology	Hradec Kralove
Czechia	Fakultni nemocnice Olomouc; Onkologicka klinika	Olomouc
Czechia	MULTISCAN, s.r.o., Radiologicke centrum Pardubice	Pardubice
Denmark	Aalborg Universitetshospital; Onkologisk Afdeling	Aalborg
Denmark	Sydvestjysk Sygehus Esbjerg; Onkologisk afdeling	Esbjerg
Denmark	Herlev Hospital; Afdeling for Kræftbehandling	Herlev
Denmark	Nordsjællands Hospital, Hillerød, Onkologisk Afdeling	Hillerod
Denmark	Rigshospitalet; Onkologisk Klinik	København Ø
Denmark	Sjællands Universitetshospital, Næstved; Onkologisk Afdeling	Naestved
Denmark	Odense Universitetshospital, Onkologisk Afdeling R	Odense C
Denmark	Sygehus Syd Roskilde; Onkologisk/haematologisk ambulatorium	Roskilde
Denmark	Vejle Sygehus; Onkologisk Afdeling	Vejle
El Salvador	Hospital Oncologia; Oncology	Salvador
El Salvador	Hospital Diagnostico Escalón	San Salvador
France	Clinique De L Europe; Pmsi	Amiens
France	ICO Paul Papin; Oncologie Medicale.	Angers
France	HOP Prive Arras Les Bonnettes; Chimiotherapie	Arras
France	Institut Sainte Catherine	Avignon
France	ICONE	Bezannes
France	Institut Bergonie; Oncologie	Bordeaux
France	Polyclinique Bordeaux Nord	Bordeaux
France	Hopital Augustin Morvan; Federation De Cancerologie	Brest
France	Centre Francois Baclesse; Recherche Clinique	Caen
France	Centre Jean Perrin; Hopital De Jour	Clermont Ferrand
France	Centre Leonard De Vinci;Chimiotherapie	Dechy
France	Centre Georges-François Lecler; Ctr de Lutte Contre le Canc	Dijon
France	Institut Daniel Hollard	Grenoble
France	Centre Hospitalier Departemental Les Oudairies	La Roche Sur Yon
France	Clinique des Ormeaux; Oncologie	Le Havre
France	Centre Oscar Lambret; Cancerologie Gynecologique	Lille
France	Hopital Dupuytren; Oncologie Medicale	Limoges
France	Centre Leon Berard; Departement Oncologie Medicale	Lyon
France	Institut Paoli Calmettes; Oncologie Medicale	Marseille
France	Institut régional du Cancer Montpellier	Montpellier
France	Polyclinique De Gentilly; Hemodialyse	Nancy
France	Centre Antoine Lacassagne; Hopital De Jour A2	Nice
France	Institut de cancerologie du Gard	Nimes
France	Ch Pitie Salpetriere; Cmrr Ile De France Salpetriere	Paris
France	Institut Curie; Oncologie Medicale	Paris
France	Polyclinique Francheville; MED CHIMIOTHERAPIE RADIOTHERAPIE	Perigueux
France	Clinique Armoricaine Radiologie; Hopital de Jour	Plerin
France	Chu De Poitiers; Chu La Miletrie	Poitiers
France	Institut Jean Godinot; Hopital De Jour	Reims
France	Centre Eugene Marquis; Unite Huguenin	Rennes
France	Centre Henri Becquerel; Oncologie Medicale	Rouen
France	Ico Rene Gauducheau; Oncologie	Saint Herblain
France	ICL; Hematologie	Saint-Priest en Jarez
France	Centre Rene Huguenin; CONSULT SPECIALISEES	St Cloud
France	Hopital Hautepierre; Hematologie Oncologie	Strasbourg
France	Institut d'oncologie de l'Orangerie; Chimiotherapie	Strasbourg
France	Clinique Pasteur; Pneumologie	Toulouse
France	Institut Claudius Regaud; Departement Oncologie Medicale	Toulouse
France	Centre Alexis Vautrin; Oncologie Medicale	Vandoeuvre-les-nancy
France	Institut Gustave Roussy; Oncologie Medicale	Villejuif
Germany	Gesundheitszentrum St. Marien GmbH; Med. II, Hämatologie/Onkologie	Amberg
Germany	Hochwaldkrankenhaus	Bad Nauheim
Germany	Evang. Krankenhaus Frauenklinik	Bergisch Gladbach
Germany	Frauenarzt-Zentrum Zehlendorf an der Teltower Eiche	Berlin
Germany	HELIOS Klinikum Berlin-Buch; Klinik für Gynäkologie und Geburtshilfe	Berlin
Germany	Praxis Dr. Schoenegg	Berlin
Germany	Praxisklinik Krebsheilkunde für Frauen / Brustzentrum (Dres. Kittel/Klare)	Berlin
Germany	Onkologische Schwerpunktpraxis Bielefeld; Haemotologie & Internistische onkologie	Bielefeld
Germany	Klinikum Sindelfingen-Böblingen; Frauenklinik	Böblingen
Germany	Universitätsklinikum Bonn; Zentrum für Geburtshilfe und Frauenheilkunde	Bonn
Germany	Praxis Dr. Ralf Lorenz	Braunschweig
Germany	Hämato-Onkologie im Medicum/Home	Bremen
Germany	Klinikum Chemnitz gGmbH; Frauen- und Kinderklinik	Chemnitz
Germany	DONAU ISAR Klinikum Deggendorf; Frauenklinik	Deggendorf
Germany	St. Johannes-Hospital	Dortmund
Germany	Universitätsklinikum "Carl Gustav Carus"; Frauenheilkunde und Geburtshilfe	Dresden
Germany	Luisenkrankenhaus GmbH & Co. KG., Brustzentrum	Düsseldorf
Germany	Universitätsklinikum Düsseldorf; Frauenklinik	Düsseldorf
Germany	Praxis für Hamatologie und Onkologie	Erfurt
Germany	Universitätsklinikum Erlangen; Frauenklinik	Erlangen
Germany	Klinikum Esslingen; Klinik für Frauenheilkunde und Geburtshilfe	Esslingen
Germany	Klinik Johann Wolfgang von Goethe Uni; Klinik für Frauenheilkunde und Geburtshilfe	Frankfurt
Germany	Städtische Kliniken Frankfurt am Main Höchst	Frankfurt
Germany	Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus	Frankfurt am Main
Germany	Praxis für Interdisziplinäre Onkologie und Hämatologie GbR	Freiburg
Germany	Dres.Jochen Wilke und Harald Wagner	Fürth
Germany	Universitätsklinikum Greifswald; Klinik für Frauenheilkunde und Brustzentrum	Greifswald
Germany	Universitätsklinikum Halle (Saale); Universitätsklinik Und Poliklinik Für Gynäkologie	Halle
Germany	Universitätsklinikum Hamburg-Eppendorf; Frauenklinik	Hamburg
Germany	SANA Klinikum Hameln-Pyrmont; Frauenklinik / Brustzentrum	Hameln
Germany	Diakovere Henriettenstift, Frauenklinik	Hannover
Germany	MVZ Onko Medical GmbH Hannover, Ralf Lohse (Geschäftsführer)	Hannover
Germany	Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg	Heidelberg
Germany	Praxisgemeinschaft; Frauenärzte am Bahnhofsplatz	Hildesheim
Germany	Universitätsklinikum des Saarlandes; Klinik f. Frauenheilkunden und Geburtshilfe	Homburg/Saar
Germany	ViDia Christliche Kliniken Karlsruhe, Vincentius-Diakonissen-Kliniken gAG; Frauenklinik	Karlsruhe
Germany	Elisabeth-Krankenhaus Brustzentrum	Kassel
Germany	Klinikum Kassel GmbH; Klinik für Frauenheilkunde und Geburtshilfe	Kassel
Germany	UNI-Klinikum Campus Kiel Klinik für Gynäkologie und Geburtshilfe	Kiel
Germany	St. Elisabeth Krankenhaus Köln GmbH; Gynäkologie und Geburtshilfe	Koeln
Germany	Uniklinik Köln, Klinik und Poliklinik und Geburtshilfe; Brustzentrum Köln	Köln
Germany	Klinikum Landshut Frauenklinik	Landshut
Germany	Sankt Elisabeth Krankenhaus; Gynaekology	Leipzig
Germany	Universitätsklinikum Schleswig-Holstein / Campus Lübeck; Klinik für Frauenheilkunde und Geburtshilfe	Lübeck
Germany	Evangelisches Krankenhaus; Abt. Gynäkologie und Geburtshilfe	Ludwigsfelde
Germany	Universitätsmedizin Mainz; Klinik u. Poliklinik f. Geburtshilfe u. Frauenheilkunde	Mainz
Germany	Brustzentrum Rhein-Ruhr Servicegesellschaft mbH	Mönchengladbach
Germany	Rotkreuzklinikum München; Frauenklinik	Muenchen
Germany	Klinikum der Universität München; Frauenklinik - Onkologie II	München
Germany	Klinikum rechts der Isar der TU München; Klinik und Poliklinik für Frauenheilkunde	München
Germany	Universitätsklinikum Münster; Klinik für Frauenheilkunde und Geburtshilfe	Münster
Germany	Sana Klinikum Offenbach GmbH; Klinik für Gynäkologie & Geburtshilfe	Offenbach
Germany	Medizinisches Versorgungszentrum am Klinikum Oldenburg GmbH	Oldenburg
Germany	Hämatologisch/Onkologische Praxis Prof. Dr. Decker, Studienzentrum	Ravensburg
Germany	Oncologianova GmbH	Recklinghausen
Germany	RoMed Klinikum Rosenheim; Klinik für Gynäkologie und Geburtshilfe	Rosenheim
Germany	Universitätsfrauen- und Poliklinik am Klinikum Suedstadt	Rostock
Germany	MVZ für Hämatologie, Onkologie, Strahlentherapie und Palliativmedizin -; Klinik Dr. Hancken	Stade
Germany	Klinikum Mutterhaus der Borromaeerinnen gGmbH; Haematologie/Onkologie	Trier
Germany	Universitätsklinik Tübingen; Frauenklinik	Tübingen
Germany	Universitätsklinikum Ulm Am Michelsberg; Frauenklinik	Ulm
Germany	Dres. Arnd Nusch Naser Ali-Mohammad Kalhori und Werner Langer	Velbert
Germany	Schwarzwald-Baar Klinikum Klinik für Frauenheilkunde und Geburtshilfe	Villingen-Schwenningen
Germany	St. Josefs-Hospital Wiesbaden	Wiesbaden
Germany	Marien-Hospital Witten; Frauenklinik Brustzentrum	Witten
Germany	Hämatologisch-Onkologische Schwerpunktpraxis Dres. Schlag & Schöttker	Würzburg
Guatemala	Centro Oncológico Sixtino / Centro Oncológico SA	Guatemala
Guatemala	Grupo Angeles	Guatemala City
Hong Kong	Queen Mary Hospital; Dept of Medicine	Hong Kong
Hong Kong	Queen Mary Hospital; Surgery	Hong Kong
Hungary	Magyar Honvedseg Egeszsegugyi Kozpont; Fázis I-es Klinikai Farmakológiai Vizsgálóhely	Budapest
Hungary	Orszagos Onkologiai Intezet; B Belgyogyaszati Osztaly	Budapest
Hungary	Semmelweis Egyetem Onkologiai Központ	Budapest
Hungary	Debreceni Egyetem, Klinikai Kozpont, Onkologiai Klinika	Debrecen
Hungary	Petz Aladar Megyei Oktato Korhaz; Oncoradiologia	Gyor
Hungary	Békés Megyei Pándy Kálmán Kórház; Onkologiai tanszek	Gyula
Hungary	Bács-Kiskun Vármegyei Oktatókórház	Kecskemet
Hungary	Szegedi Tudomanyegyetem, AOK, Szent-Gyorgyi Albert Klinikai Kozpont, Onkoterapias Klinika	Szeged
Hungary	Veszprem Megyei Csolnoky; Ferenc Korhaz	Veszprem
Ireland	Cork Uni Hospital; Oncology Dept	Cork
Ireland	Beaumont Hospital; Cancer Clinical Trials Unit	Dublin
Ireland	Mater Misericordiae Uni Hospital; Oncology	Dublin
Ireland	St Vincent'S Uni Hospital; Medical Oncology	Dublin
Ireland	St. James Hospital; Oncology	Dublin
Ireland	Galway University Hospital; Clinical Trials Department	Galway
Ireland	University Hospital Limerick - Oncology	Limerick
Israel	Rambam Medical Center; Oncology	Haifa
Israel	Rabin MC; Davidof Center - Oncology Institute	Petach Tikva
Israel	Chaim Sheba Medical Center; Oncology Dept	Ramat Gan
Israel	Kaplan Medical Center; Oncology Inst.	Rehovot
Israel	Sourasky / Ichilov Hospital; Oncology Department	Tel Aviv
Italy	AORN'S.G.Moscati; Oncologia	Avellino	Campania
Italy	Irccs Centro Di Riferimento Oncologico (CRO); Dipartimento Di Oncologia Medica	Aviano	Friuli-Venezia Giulia
Italy	Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica	Bologna	Emilia-Romagna
Italy	Ospedale Di Bolzano; Dept. Di Oncologia	Bolzano	Trentino-Alto Adige
Italy	ASST DEGLI SPEDALI CIVILI DI BRESCIA; Oncologia Medica	Brescia	Lombardia
Italy	Ospedale Antonio Perrino; Oncologia Medica	Brindisi	Puglia
Italy	Fondazione Del Piemonte Per L'oncologia Ircc Di Candiolo; Dipartimento Oncologico	Candiolo	Piemonte
Italy	Ospedale Ramazzini	Carpi	Emilia-Romagna
Italy	Campus Universitario S.Venuta; Centro Oncologico T.Campanella	Catanzaro	Calabria
Italy	Ospedale S. Croce Di Fano; Servizio Oncologia	Fano	Marche
Italy	Az. Osp. Uni Ria San Martino; Cliniche Uni Rie Convenzionate U.O. Oncologia Medical	Genova	Liguria
Italy	Ente Ospedaliero Ospedali Galliera; S.C. Oncologia Medica	Genova	Liguria
Italy	IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A	Genova	Liguria
Italy	ASST DI LECCO; Oncologia Medica	Lecco	Lombardia
Italy	Ospedale Mater Salutis; Dept of Oncology	Legnago	Veneto
Italy	Irccs Istituto Europeo Di Oncologia (IEO); Ricerca Di Senologia Medica	Milano	Lombardia
Italy	Policlinico di Monza; Istituto di Oncologia	Monza	Lombardia
Italy	IRCCS Istituto Nazionale Tumori Fondazione Pascale; Oncologia Medica A	Napoli	Campania
Italy	Ist. Uni Federico Ii; Divisione Di Oncologia Medica - Dpt. Di Medicina Interna	Napoli	Campania
Italy	IRCCS Fondazione Maugeri; Oncologia Medica I	Pavia	Lombardia
Italy	Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; Oncologia Medica	Perugia	Umbria
Italy	Nuovo Ospedale di Prato S. Stefano - Azienda USL Toscana Centro	Prato	Toscana
Italy	Arcispedale Santa Maria Nuova; Oncologia	Reggio Emilia	Emilia-Romagna
Italy	IRCCS Istituto Clinico Humanitas; Oncologia	Rozzano (MI)	Lombardia
Italy	Az. Osp. Di Busto P.O. Di Saronno; U.O. Di Oncologia Medica	Saronno	Lombardia
Italy	Azienda Ospedaliera S. Maria - Terni; Oncologia	Terni	Umbria
Italy	Divisione Onc Med dell'Azienda	Udine	Friuli-Venezia Giulia
Italy	Ospedale Belcolle Di Viterbo; Oncologia	Viterbo	Lazio
Japan	Aichi Cancer Center Hospital, Breast Oncology	Aichi
Japan	Chiba Cancer Center; Breast Surgical Oncology	Chiba
Japan	National Cancer Center Hospital East	Chiba
Japan	Natl Hosp Org Shikoku; Cancer Ctr, Surgery	Ehime
Japan	National Hospital Organization Kyushu Cancer Center;Breast Oncology	Fukuoka
Japan	Gunma University Hospital; Department of Thoracic and Visceral Organ Surgery	Gunma
Japan	Hiroshima City Hiroshima Citizens Hospital; Breast Surgery	Hiroshima
Japan	Iwate Med Univ School of Med; Surgery	Iwate
Japan	Sagara Hospital; Breast Surgery	Kagoshima
Japan	St. Marianna University School of Medicine Hospital, Breast and Endocrine Surgery	Kanagawa
Japan	Tokai University Hospital, Breast Surgery	Kanagawa
Japan	Kumamoto City Hospital, Breast and Endocrine Surgery	Kumamoto
Japan	Kumamoto Shinto General Hospital; Breast Cancer Center	Kumamoto
Japan	Kyoto University Hospital; Breast Surgery	Kyoto
Japan	Niigata Cancer Ctr Hospital; Breast Surgery	Niigata
Japan	National Hospital Organization Osaka National Hospital; Breast Surgery	Osaka
Japan	Osaka International Cancer Institute; Breast and Endocrine Surgery	Osaka
Japan	Saitama Cancer Center, Breast Oncology	Saitama
Japan	Saitama Medical University International Medical Center; Breast Oncology	Saitama
Japan	Shizuoka Cancer Center; Breast Surgery	Shizuoka
Japan	Shizuoka General Hospital; Breast Surgery	Shizuoka
Japan	Jichi Medical School ; Surgery	Tochigi
Japan	National Cancer Center Hospital; Medical Oncology	Tokyo
Japan	The Cancer Inst. Hosp. of JFCR; Breast Oncology Center	Tokyo
Japan	Tokyo Medical Uni. Hospital; Breast Oncology	Tokyo
Japan	Tokyo Metropolitan; Komagome Hospital, Surgery	Tokyo
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Korea University Anam Hospital; Oncology Haemotology	Seoul
Korea, Republic of	Kyunghee University Hospital; Endocrinology	Seoul
Korea, Republic of	Samsung Medical Centre; Division of Hematology/Oncology	Seoul
Korea, Republic of	Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology	Seoul
Korea, Republic of	Yonsei University Severance Hospital; Medical Oncology	Seoul
Mexico	Médicos Especialistas en Cáncer SC	Aguascalientes
Mexico	Centro Estatal de Oncología de Campeche	Campehe	Campeche
Mexico	Centro Estatal De Cancerologia De Durango; Oncology	Durango
Mexico	Núcleo de Especialidades Oncológicas	Guadalajara	Jalisco
Mexico	Fundacion Rodolfo Padilla Padilla A.C.	León	Guanajuato
Mexico	Hospital Angeles Metropolitano; Room 220	Mexico City	Mexico CITY (federal District)
Mexico	Hospital General de México; Unidad de Oncologia	Mexico DF	Mexico CITY (federal District)
Mexico	Centro Universitario Contra El Cancer	Monterrey	Nuevo LEON
Mexico	Centro de Diagnóstico y Tratamiento Integral de Mama, Hospital San José Tec de Monterrey	Montrrey	Nuevo LEON
Mexico	Oaxaca Site Management Organization	Oaxaca de Juárez	Oaxaca
Mexico	Cancerologia de Queretaro; Oncologia	Queretaro, Queretaro	Queretaro
Mexico	Centro Regional de Enfermedades Oncológicas, S.A.	San Luis Potosi
Netherlands	Medisch Centrum Alkmaar	Alkmaar
Netherlands	Amphia ziekenhuis, locatie langendijk	Breda
Netherlands	Reinier de Graaf Gasthuis	Delft
Netherlands	Academish Ziekenhuis Maastricht (Azm); Inwendige Geneeskunde	Maastricht
Netherlands	Isala Klinieken	Zwolle
New Zealand	Waikato Hospital; Dept of Medical Oncology	Hamilton
New Zealand	Palmerston North Hospital; Regional Cancer Treatment Service	Palmerston North
Panama	Centro Oncologico America	Panama
Panama	The Panama Clinic	Panama
Peru	Clinica Anglo Americana - Centro de Investigacion Oncologia CAA	Lima
Peru	Instituto Nacional de Enfermedades Neoplasicas	Lima
Peru	Clinica El Golf	San Isidro
Peru	Clinica Peruana Americana	Trujillo
Philippines	University Of Santo Tomas; Oncology; Benavides Cancer Institute	Manila
Philippines	Rizal Medical Center	Pasig City
Philippines	Veterans Memorial Medical Ctr; Cancer Research Centre	Quezon City
Poland	Bialostockie Ctr Onkologii; Oddzial Chemioterapii Dziennej	Bialystok
Poland	Centrum Onkologii;Im. Franciszka Lukaszczyka;Onkologii	Bydgoszcz
Poland	Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii	Gdansk
Poland	Opolskie Centrum Onkologii;Oddzial Onkologii Klinicznej	Opole
Poland	Narodowy Inst.Onkologii im.Sklodowskiej-Curie Panstw.Inst.Bad; Klinika Nowtw.Piersi i Chir.Rekonstr	Warszawa
Poland	NZOZ Mazowiecki Szpital Onkologiczny Uczelni Warszawskiej im. M. Sk?odowskiej-Curie	Wieliszew
Romania	Emergency University Bucharest Hospital; Oncology Department	Bucharest
Romania	Prof. Dr. I. Chiricuta Institute of Oncology	Cluj Napoca
Romania	Oncology Inst. Cluj-Napoca; Cancer Dept	Cluj-Napoca
Romania	Euroclinic Center of Oncology SRL	Iasi
Russian Federation	Clinical Oncology Dispensary of Ministry of Health of Tatarstan	Kazan	Tatarstan
Russian Federation	S.I. Russian Oncological Research Center n.a. N.N. Blokhin	Moscow	Moskovskaja Oblast
Russian Federation	State Budget Institution of Healthcare of Stavropol region Pyatigorsk Oncology Dispensary	Pyatigorsk	Stavropol
Russian Federation	SBI of Healthcare Samara Regional Clinical Oncology Dispensary	Samara
Russian Federation	SBI of Healthcare of Stavropol region Stavropol Regional Clinical Oncology Dispensary	Stavropol
Russian Federation	Tula Regional Oncology Dispensary	Tula
Slovenia	Institute of Oncology Ljubljana	Ljubljana
South Africa	National Hospital; Oncotherapy Dept	Bloemfontein
South Africa	Wits Donald Gordon Clinical Trial Centre; Medical Oncology	Johannesburg
South Africa	Steve Biko Academic Hospital; Oncology	Pretoria
Spain	Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia	Badalona	Barcelona
Spain	Hospital Clínic i Provincial; Servicio de Hematología y Oncología	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia	Barcelona
Spain	Hospital del Mar; Servicio de Oncologia	Barcelona
Spain	Hospital Duran i Reynals; Oncologia	Barcelona
Spain	Hospital Provincial de Castellon; Servicio de Oncologia	Castellon de La Plana	Castellon
Spain	Hospital Universitario Reina Sofia; Servicio de Oncologia	Córdoba	Cordoba
Spain	Hospital General Universitario de Elche; Servicio de Oncologia	Elche	Alicante
Spain	Hospital Juan Ramon Jimenez;Servicio de Oncologia	Huelva
Spain	Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico; Servicio de Oncologia	Jaen
Spain	Centro Oncológico Gallego José Antonio Quiroga y Piñeiro, Servicio de Oncologia	La Coruña
Spain	Complejo Hospitalario Universitario A Coruña (CHUAC, Materno Infantil), Oncología	La Coruña
Spain	Hospital Universitario de Canarias;servicio de Oncologia	La Laguna	Tenerife
Spain	Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Oncologia	Lerida
Spain	Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica	Madrid
Spain	Centro Oncologico MD Anderson Internacional; Servicio de Oncologia	Madrid
Spain	Hospital General Universitario Gregorio Marañon; Servicio de Oncologia	Madrid
Spain	Hospital Ramon y Cajal; Servicio de Oncologia	Madrid
Spain	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid
Spain	Hospital Universitario Clínico San Carlos; Servicio de Oncologia	Madrid
Spain	Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia	Malaga
Spain	Hospital General Universitario J.M Morales Meseguer; Servicio de Oncologia	Murcia
Spain	Hospital Son Llatzer; Servicio de Oncologia	Palma de Mallorca	Islas Baleares
Spain	Hospital Universitario Son Espases	Palma De Mallorca	Islas Baleares
Spain	Corporacio Sanitaria Parc Tauli; Servicio de Oncologia	Sabadell	Barcelona
Spain	Hospital Clinico Universitario de Salamanca; Servicio de Oncologia	Salamanca
Spain	Hospital de Donostia; Servicio de Oncologia Medica	San Sebastian	Guipuzcoa
Spain	IInstituto Oncologico de San Sebastian, Oncologikoa; Servicio de Oncologia	San Sebastian	Guipuzcoa
Spain	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Sant Andreu de La Barca	Barcelona
Spain	Hospital Universitario Marques de Valdecilla; Servicio de Oncologia	Santander	Cantabria
Spain	Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia	Santiago de Compostela	LA Coruña
Spain	Hospital Univ. Nuestra Señora de Valme; Servicio de Oncologia	Sevilla
Spain	Hospital Universitario Virgen del Rocio; Servicio de Oncologia	Sevilla
Spain	Hospital Universitario Virgen Macarena; Servicio de Oncologia	Sevilla
Spain	Complejo Hospitalario de Toledo- H. Virgen de la Salud; Servicio de Oncologia	Toledo
Spain	Hospital Arnau de Vilanova (Valencia) Servicio de Oncologia	Valencia
Spain	Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia	Valencia
Spain	Hospital Universitario la Fe; Servicio de Oncologia	Valencia
Spain	Instituto Valenciano Oncologia; Oncologia Medica	Valencia
Spain	Hospital Universitario Miguel Servet; Servicio Oncologia	Zaragoza
Sweden	Sahlgrenska Universitetssjukhuset; Onkology	Gothenburg
Sweden	Uni Hospital Linkoeping; Dept. of Oncology	Linköping
Sweden	Karolinska University Hospital; Department of General Oncology	Stockholm
Sweden	Norrlands Universitetssjukhus, Umeå, Cancercentrum; Dept of Oncology	Umea
Sweden	Akademiska sjukhuset, Onkologkliniken	Uppsala
Switzerland	Universitaetsspital Basel; Onkologie	Basel
Switzerland	Hôpitaux Universit. de Genève Gynécologique - Oncologie; Gynécologie	Genève 14
Switzerland	Luzerner Kantonsspital; Medizinische Onkologie	Luzern
Switzerland	Kantonsspital St. Gallen; Onkologie/Hämatologie	St. Gallen
Switzerland	Brust-Zentrum Zürich AG Seefeldstrasse 214 Zürich	Zürich
Taiwan	Changhua Christian Hospital; Dept of Surgery	Changhua
Taiwan	Kaohsiung Medical Uni Chung-Ho Hospital; Dept of Surgery	Kaohsiung
Taiwan	Taichung Veterans General Hospital; Dept of Surgery	Taichung
Taiwan	National Cheng Kung Uni Hospital; Surgery	Tainan
Taiwan	National Taiwan Uni Hospital; General Surgery	Taipei
Taiwan	Tri-Service General Hospital, Division of General Surgery	Taipei
Taiwan	VETERANS GENERAL HOSPITAL; Department of General Surgery	Taipei
Thailand	Chiang Rai Prachanukraw Hospital; Department of Pediatrics, Faculty of Medicine	Chiang Rai
Thailand	Lopburi Cancer Hospital; Chemotherpy Unit; Chemotherapy	Lopburi
Thailand	Buddhachinaraj Phitsanulok Hospital; Chemotherapy Unit ; Department of Medicine	Phitsanuok
Thailand	Songklanagarind Hospital; Department of Surgery	Songkla
Thailand	Surat Thani Hospital	Surat Thani
Ukraine	Cherkassy Regional Oncological Hospital	Cherkassy
Ukraine	State Medical Academy; Oncology	Dnipropetrovsk
Ukraine	Ivano-Frankivsk Regional Oncology Center	Ivano-Frankivsk
Ukraine	Kyiv City Clinical Oncological Center, Day Hospital Department for Oncological patients	Kiev
Ukraine	Volyn Regional Oncology Dispensary	Lutsk
Ukraine	Lvov State Regional Oncology Medical & Diagnostic Center	Lvov
Ukraine	Ternopil State Medical Academy	Ternopil
United Kingdom	Royal Berkshire Hospital; Berkshire Cancer Centre	Berkshire
United Kingdom	Velindre Cancer Centre; Oncology Dept	Cardiff
United Kingdom	Cheltenham General Hospital; Gloucestershire Oncology Centre	Cheltenham
United Kingdom	Colchester General Hospital	Colchester, Essex
United Kingdom	Royal Cornwall Hospital; Dept of Clinical Oncology	Cornwall
United Kingdom	University Hospital coventry; Oncology Department	Coventry
United Kingdom	Western General Hospital; Edinburgh Breast Unit	Edinburgh
United Kingdom	Royal Devon & Exeter Hospital; Oncology Centre	Exeter
United Kingdom	Ipswich Hospital; Oncology Pharmacy	Ipswich
United Kingdom	St James Uni Hospital; Icrf Cancer Medicine Research Unit	Leeds
United Kingdom	Royal Marsden Hospital; Dept of Med-Onc	London
United Kingdom	St. Bartholomew'S Hospital; Dept of Medical Oncology	London
United Kingdom	UCL Hospital NHS Trust	London
United Kingdom	Christie Hospital; Breast Cancer Research Office	Manchester
United Kingdom	Mount Vernon Hospital; Centre For Cancer Treatment	Northwood
United Kingdom	Nottingham City Hospital; Oncology	Nottingham
United Kingdom	Churchill Hospital; Oxford Cancer and Haematology Centre	Oxford
United Kingdom	Peterborough City Hospital, Edith Cavell Campus; Oncology Department	Peterborough
United Kingdom	Queen Alexandra Hospital; Haematology and Oncology Centre	Portsmouth
United Kingdom	Royal Preston Hosp; Rosemere Cancer Ctr	Preston
United Kingdom	Weston Park Hospital; Cancer Clinical Trials Centre	Sheffield
United Kingdom	Uni Hospital of North Staffordshire; Staffordshire Oncology Centre	Stoke-on-Trent
United Kingdom	Royal Marsden Hosp NHS Fnd; Medicine - Breast Unit	Sutton
United Kingdom	The Clatterbridge Cancer Ctr For Oncolgy	Wirral
United Kingdom	New Cross Hospital; Deansley Centre	Wolverhampton
United States	New York Oncology Hematology, P.C.	Albany	New York
United States	Phoebe Putney Memorial Hospital	Albany	Georgia
United States	Georgia Cancer Specialists	Atlanta	Georgia
United States	Mercy Medical Center	Baltimore	Maryland
United States	Weinberg CA Inst Franklin Sq	Baltimore	Maryland
United States	Maryland Oncology & Hematology, PA	Bethesda	Maryland
United States	Beth Israel Deac Med Ctr; East Campus Rsch Pharmacy	Boston	Massachusetts
United States	Boston Medical Center	Boston	Massachusetts
United States	Dana Farber Can Ins	Boston	Massachusetts
United States	Dana Farber Cancer Institute at Faulkner Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital.	Boston	Massachusetts
United States	Cancer Care of Maine	Brewer	Maine
United States	Wellmonth Physician Services	Bristol	Virginia
United States	Montefiore Medical Center	Bronx	New York
United States	Roswell Park Cancer Inst.	Buffalo	New York
United States	Dayton Clinical Oncology Prog	Centerville	Ohio
United States	University of North Carolina-Chapel Hill	Chapel Hill	North Carolina
United States	Charleston Oncology, P .A	Charleston	South Carolina
United States	Roper Bon Secours St. Francis Cancer Center	Charleston	South Carolina
United States	Tennessee Oncology , PLLC - Chattanooga	Chattanooga	Tennessee
United States	Rush University Medical Center	Chicago	Illinois
United States	Uni of Chicago	Chicago	Illinois
United States	Oncology Hematology Care Inc	Cincinnati	Ohio
United States	South Carolina Oncology Associates - SCRI	Columbia	South Carolina
United States	The Mark H. Zangmeister Ctr; Mid Ohio Onc/Hem Inc.	Columbus	Ohio
United States	Texas Oncology - DFW	Dallas	Texas
United States	Texas Oncology - DFW at Dallas Presbyterian Hospital	Dallas	Texas
United States	Texas Oncology-Medical City Dallas	Dallas	Texas
United States	Southdale Cancer Clinic	Edina	Minnesota
United States	Texas Oncology-El Paso Cancer Treatment Center Grandview	El Paso	Texas
United States	Providence Regional Medical Center	Everett	California
United States	Florida Cancer Specialists; SCRI	Fort Myers	Florida
United States	Texas Oncology - DFW Fort Worth	Fort Worth	Texas
United States	The Center for Cancer and Blood Disorders - Fort Worth	Fort Worth	Texas
United States	Texas Oncology, P.A. - Garland	Garland	Texas
United States	Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan
United States	Green Bay Oncology/St. Mary?s Hospital	Green Bay	Wisconsin
United States	Marin Cancer Care Inc	Greenbrae	California
United States	Cancer Centers of the Carolina; Eastside Medical Center	Greenville	South Carolina
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	Kaiser Permanente - Hayward	Hayward	California
United States	Carolina Oncology Specialists, PA - Hickory	Hickory	North Carolina
United States	Memorial Cancer Institute	Hollywood	Florida
United States	Texas Oncology - Houston (Gessner)	Houston	Texas
United States	University of Iowa	Iowa City	Iowa
United States	Texas Oncology-Tyler	Irving	Texas
United States	Jackson Oncology Associates, PLLC	Jackson	Mississippi
United States	Cancer Specialists; North Florida ;Jacksonville (AC Skinner Pkwy)	Jacksonville	Florida
United States	Mayo Clinic-Jacksonville	Jacksonville	Florida
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	University of Missouri-Columbia; Ellis Fischel Cancer Center	Kansas City	Missouri
United States	UCSD Moores Cancer Center	La Jolla	California
United States	Cancer Center of Acadiana at Lafayette General	Lafayette	Louisiana
United States	Dartmouth Hitchcock Med Center	Lebanon	New Hampshire
United States	Cancer Alliance of Nebraska	Lincoln	Nebraska
United States	Rocky Mountain Cancer Center - Denver	Littleton	Colorado
United States	Saint Barnabas Medical Center	Livingston	New Jersey
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Northwest Georgia Oncology Centers PC - Marietta	Marietta	Georgia
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	Loyola University Med Center	Maywood	Illinois
United States	West Virginia University Hospitals Inc	Morgantown	West Virginia
United States	Edward Cancer Center Naperville	Naperville	Illinois
United States	Tennessee Oncology - Nashville	Nashville	Tennessee
United States	Vanderbilt Breast Center at One Hundred Oaks	Nashville	Tennessee
United States	Cancer Care Centers of South Texas-HOAST - San Antonio	New Braunfels	Texas
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mount Sinai Beth Israel Comprehensive Cancer Center	New York	New York
United States	Mount Sinai Beth Israel Medical Center	New York	New York
United States	Mount Sinai West	New York	New York
United States	Eastern Ct Hema/Onco Assoc; Dept of Oncology	Norwich	Connecticut
United States	Kaiser Permanente - Oakland	Oakland	California
United States	Ocala Oncology Center	Ocala	Florida
United States	Community Cancer Trials of Utah	Ogden	Utah
United States	Cancer Alliance of Nebraska	Omaha	Nebraska
United States	Memorial Breast Cancer Center	Pembroke Pines	Florida
United States	Illinois Cancer Care	Peoria	Illinois
United States	Abramson Cancer Center; Univ of Pennsylvania	Philadelphia	Pennsylvania
United States	Albert Einstein Healthcare Network ; Cancer Center	Philadelphia	Pennsylvania
United States	Magee Womens Hospital	Pittsburgh	Pennsylvania
United States	Berkshire Hematology, Oncology Pc	Pittsfield	Massachusetts
United States	Edward Cancer Center Plainfield	Plainfield	Illinois
United States	Texas Oncology - DFW Plano	Plano	Texas
United States	Hematology Oncology Associates of the Treasure Coast	Port Saint Lucie	Florida
United States	Northwest Cancer Specialists - Portland (NE Hoyt St)	Portland	Oregon
United States	Kootenai Cancer Center	Post Falls	Idaho
United States	Quincy Medical Group; Canc Ctr at Blessing Hosp	Quincy	Illinois
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Kaiser Permanente - Roseville	Roseville	California
United States	Kaiser Permanente Sacramento Medical Center	Sacramento	California
United States	Sutter Cancer Center	Sacramento	California
United States	Coborn Cancer Center	Saint Cloud	Minnesota
United States	Heartland CCOP/Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Metro-Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota
United States	Florida Cancer Specialists; Saint Petersburg	Saint Petersburg	Florida
United States	Southern California Kaiser Permanente	San Diego	California
United States	K. Permanente - San Fransisco	San Francisco	California
United States	K. Permanente - San Jose	San Jose	California
United States	K. Permanente - Santa Clara	Santa Clara	California
United States	New England Cancer Specialists	Scarborough	Maine
United States	HonorHealth Research Institute ? Bisgrove	Scottsdale	Arizona
United States	Sanford USD School of Medicine	Sioux Falls	South Dakota
United States	K. Permanente - S. San Fran	South San Francisco	California
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Toledo Clinic Cancer Center	Toledo	Ohio
United States	Carle Foundation	Urbana	Illinois
United States	Kaiser Permanente; Oncology Clinical Trials	Vallejo	California
United States	Providence St. Mary Regional Cancer Center	Walla Walla	Washington
United States	K. Permanente - Walnut Creek	Walnut Creek	California
United States	Georgetown U; Lombardi Comp Can	Washington	District of Columbia
United States	Washington Cancer Institute at MedStar Washington Hospital Center.	Washington	District of Columbia
United States	Florida Cancer Specialists, Research Department	West Palm Beach	Florida
United States	Lutheran Hematology &Oncology	Wheat Ridge	Colorado
United States	Cancer Center of Kansas	Wichita	Kansas

Sponsors (3)

Lead Sponsor	Collaborator
Hoffmann-La Roche	Breast International Group, Genentech, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Bulgaria,  Canada,  Chile,  China,  Colombia,  Croatia,  Czechia,  Denmark,  El Salvador,  France,  Germany,  Guatemala,  Hong Kong,  Hungary,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  New Zealand,  Panama,  Peru,  Philippines,  Poland,  Romania,  Russian Federation,  Slovenia,  South Africa,  Spain,  Sweden,  Switzerland,  Taiwan,  Thailand,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Invasive Disease-Free Survival (IDFS) Event (Excluding Second Primary Non-Breast Cancer [SPNBC]), as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings	Percentage of participants with IDFS events (excluding SPNBC) is reported. IDFS event was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (that is [i.e.], an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer. All SPNBCs and in situ carcinomas (including ductal carcinoma in situ [DCIS] and lobular carcinoma in situ [LCIS]) and non-melanoma skin cancer were excluded as an event.	Randomization to the first occurrence of IDFS event (excluding SPNBC) (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months)
Primary	Kaplan-Meier Estimate of the Percentage of Participants Who Were IDFS Event-Free (Excluding SPNBC) at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings	Kaplan-Meier estimate of the percentage of participants who were IDFS event-free (excluding SPNBC) at Year 3 is reported. IDFS event was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer. All SPNBCs and in situ carcinomas (including DCIS and LCIS) and non-melanoma skin cancer were excluded as an event.	3 years
Secondary	Percentage of Participants With IDFS Event (Including SPNBC), as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings	Percentage of participants with IDFS events (including SPNBC) is reported. IDFS-SPNBC event was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer; SPNBC (with the exception of non-melanoma skin cancers and in situ carcinoma of any site).	Randomization to the first occurrence of IDFS event (including SPNBC) (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months)
Secondary	Kaplan-Meier Estimate of the Percentage of Participants Who Were IDFS Event-Free (Including SPNBC) at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings	Kaplan-Meier estimate of the percentage of participants who were IDFS event-free (including SPNBC) at Year 3 is reported. IDFS-SPNBC was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer; SPNBC (with the exception of non-melanoma skin cancers and in situ carcinoma of any site).	3 years
Secondary	Percentage of Participants With Disease-Free Survival (DFS) Event, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings	Percentage of participants with DFS event is reported. DFS event was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer; SPNBC or contralateral or ipsilateral DCIS.	Randomization to the first occurrence of DFS event (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months)
Secondary	Kaplan-Meier Estimate of the Percentage of Participants Who Were DFS Event-Free at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings	Kaplan-Meier estimate of the percentage of participants who were DFS event-free at Year 3 is reported. DFS was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer; SPNBC or contralateral or ipsilateral DCIS.	3 years
Secondary	Percentage of Participants Who Died	Percentage of participants who died due to any cause is reported.	Randomization until death due to any cause (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months)
Secondary	Kaplan-Meier Estimate of the Percentage of Participants Who Were Alive at Year 3	The Kaplan-Meier approach was used to estimate the percentage of participants who were alive at 3 years.	3 years
Secondary	Percentage of Participants With Recurrence-Free Interval (RFI) Event, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings	Percentage of participants with RFI event is reported. RFI event was defined as local, regional or distant breast cancer recurrence.	Randomization until local, regional or distant breast cancer recurrence (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months)
Secondary	Kaplan-Meier Estimate of the Percentage of Participants Who Were RFI Event-Free at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings	Kaplan-Meier estimate of the percentage of participants who were RFI event-free at Year 3 is reported. RFI event was defined as local, regional or distant breast cancer recurrence.	3 years
Secondary	Percentage of Participants With Distant Recurrence-Free Interval (DRFI) Event, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings	Percentage of participants with DRFI event is reported. DRFI event was defined as distant breast cancer recurrence.	Randomization until distant breast cancer recurrence (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months)
Secondary	Kaplan-Meier Estimate of the Percentage of Participants Who Were DRFI Event-Free at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings	Kaplan-Meier estimate of the percentage of participants who were DRFI event-free at Year 3 is reported. DRFI event was defined as distant breast cancer recurrence.	3 years
Secondary	Percentage of Participants With Primary Cardiac Event	Primary cardiac event was defined as either: Heart Failure (New York Heart Association [NYHA] Class III or IV) and a drop in left ventricular ejection fraction (LVEF) of at least 10 ejection fraction (EF) points from baseline and to below 50 percent (%); or cardiac death. Cardiac death was defined as either definite cardiac death: due to heart failure, myocardial infarction, or documented primary arrhythmia; or probable cardiac death: sudden unexpected death within 24 hours of a definite or probable cardiac event (e.g., syncope, cardiac arrest, chest pain, infarction, arrhythmia) without documented etiology.	Baseline until data cut-off date 19 December 2016 (up to maximum length of follow-up of 59 months)
Secondary	Percentage of Participants With Secondary Cardiac Event	Secondary cardiac event was defined as asymptomatic or mildly symptomatic (NYHA Class II) significant drop in LVEF (defined as an absolute decrease of at least 10 EF points from baseline and to below 50%), confirmed by a second LVEF assessment within approximately three weeks of the first significant LVEF assessment or confirmed by the Cardiac Advisory Board (CAB).	Baseline until data cut-off date 19 December 2016 (up to maximum length of follow-up of 59 months)
Secondary	Change From Baseline in LVEF to Worst Post-Baseline Value	LVEF is the fraction of blood (in percent) pumped out of the heart's left ventricular chamber with each heart beat, and is a measure of cardiac output for the heart. Baseline LVEF value and the maximum absolute decrease (worst value) in LVEF measurement from baseline were reported. LVEF was measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan.	Baseline until data cut-off date 19 December 2016 (up to maximum length of follow-up of 59 months)
Secondary	Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) Global Health Status (GHS) Scale Score	EORTC QLQ-C30 is a cancer-specific instrument with 30 questions used to assess the overall quality of life (QOL) in cancer participants. First 28 questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, social, cognitive, emotional), 8 symptom scales/items (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea and vomiting [N/V], constipation, and pain) and a single item (financial difficulties). Last 2 questions represented participant's assessment of overall health and quality of life, used 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 global scores were linearly transformed on a scale of 0 to 100, with a high score indicating better GHS/QOL. Negative change from Baseline values indicated deterioration in QOL or functioning and positive values indicated improvement.	Baseline, Weeks 13, 25; end of treatment (EOT, 28 days after the last dose, up to Week 56); Follow-up (FU) Months 18, 24, 36
Secondary	Change From Baseline in EORTC QLQ-C30 Functioning Subscale Scores	EORTC QLQ-C30 is a cancer-specific instrument with 30 questions used to assess the overall QOL in cancer participants. First 28 questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, social, cognitive, emotional), 8 symptom scales/items (diarrhea, fatigue, dyspnea, appetite loss, insomnia, N/V, constipation, and pain) and a single item (financial difficulties). Last 2 questions represented participant's assessment of overall health and quality of life, coded on 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 functioning scores were linearly transformed on a scale of 0 to 100, with a high score indicating better functioning/support. Negative change from Baseline values indicated deterioration in functioning and positive values indicated improvement.	Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36
Secondary	Change From Baseline in EORTC QLQ-C30 Disease/Treatment-Related Symptoms Subscale Scores	EORTC QLQ-C30 is a cancer-specific instrument with 30 questions used to assess the overall QOL in cancer participants. First 28 questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, social, cognitive, emotional), 8 symptom scales/items (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea and vomiting [N/V], constipation, and pain) and a single item (financial difficulties). Last 2 questions represented participant's assessment of overall health and quality of life, coded on 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 disease/treatment-related symptom scores were linearly transformed on a scale of 0 to 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicated improvement in symptoms and positive values indicated worsening of symptoms.	Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36
Secondary	Change From Baseline in EORTC QLQ-C30 Financial Difficulties Subscale Scores	EORTC QLQ-C30 is a cancer-specific instrument with 30 questions used to assess the overall QOL in cancer participants. First 28 questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, social, cognitive, emotional), 8 symptom scales/items (diarrhea, fatigue, dyspnea, appetite loss, insomnia, N/V, constipation, and pain) and a single item (financial difficulties). Last 2 questions represented participant's assessment of overall health and quality of life, coded on 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 financial difficulties scores were linearly transformed on a scale of 0 and 100, with a high score indicating a higher level of financial difficulties. Negative change from Baseline values indicated improvement in financial difficulties and positive values indicated worsening of financial difficulties.	Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36
Secondary	Change From Baseline in European Organisation for Research and Treatment of Cancer - Breast Cancer Module Quality of Life (EORTC QLQ-BR23) Functional Scale Score	EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of 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. Negative change from Baseline indicated deterioration in QOL and positive change from Baseline indicated an improvement in QOL.	Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36
Secondary	Change From Baseline in EORTC QLQ-BR23 Symptom Scale Score	EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of 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 symptom scale indicated high level of symptomatology/problems/greater degree of symptoms. Negative change from Baseline indicated deterioration in QOL and positive change from Baseline indicated an improvement in QOL.	Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36
Secondary	Percentage of Participants With Response for European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Domain	EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions/domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems [scored as 1], some or moderate problems [scored as 2], and extreme problems [scored as 3]). Percentage of participants with each of the following responses in mobility domain was reported: I have no problems in walking about; I have some problems in walking about; and I am confined to bed. Response percentages may not add up to 100% due to data rounding.	Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36
Secondary	Percentage of Participants With Response for EQ-5D-3L Questionnaire: Self-Care Domain	EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions/domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems [scored as 1], some or moderate problems [scored as 2], and extreme problems [scored as 3]). Percentage of participants with each of the following responses in self-care domain was reported: I have no problems with self-care; I have some problems washing or dressing myself; and I am unable to wash or dress myself. Response percentages may not add up to 100% due to data rounding.	Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36
Secondary	Percentage of Participants With Response for EQ-5D-3L Questionnaire: Usual Activities Domain	EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions/domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems [scored as 1], some or moderate problems [scored as 2], and extreme problems [scored as 3]). Percentage of participants with each of the following responses in usual activities domain was reported: I have no problems with performing my usual activities; I have some problems with performing my usual activities; and I am unable to perform my usual activities. Response percentages may not add up to 100% due to data rounding.	Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36
Secondary	Percentage of Participants With Response for EQ-5D-3L Questionnaire: Pain/Discomfort Domain	EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions/domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems [scored as 1], some or moderate problems [scored as 2], and extreme problems [scored as 3]). Percentage of participants with each of the following responses in pain/discomfort domain was reported: I have no pain or discomfort; I have moderate pain or discomfort; and I have extreme pain or discomfort. Response percentages may not add up to 100% due to data rounding.	Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36
Secondary	Percentage of Participants With Response for EQ-5D-3L Questionnaire: Anxiety/Depression Domain	EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions/domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems [scored as 1], some or moderate problems [scored as 2], and extreme problems [scored as 3]). Percentage of participants with each of the following responses in anxiety/depression domain was reported: I am not anxious or depressed; I am moderately anxious or depressed; and I am extremely anxious or depressed. Response percentages may not add up to 100% due to data rounding.	Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36
Secondary	Trough Serum Concentration (Cmin) of Pertuzumab		Cycles 1, 10 and 15 (Cycle length=21 days)
Secondary	Cmin of Trastuzumab		Cycles 1, 10 and 15 (Cycle length=21 days)
Secondary	Peak Serum Concentration (Cmax) of Pertuzumab		Cycles 1, 10 and 15 (Cycle length=21 days)
Secondary	Cmax of Trastuzumab		Cycles 1, 10 and 15 (Cycle length=21 days)