A Study of a Combination of Trastuzumab and Capecitabine With or Without Pertuzumab in Patients With HER2-positive Metastatic Breast Cancer (PHEREXA)

NCT ID: NCT01026142

Last Updated: 2018-08-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 452 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-26
• Study Completion Date: 2017-08-07

Brief Summary

This randomized, two-arm study evaluated the efficacy and safety of a combination of trastuzumab and capecitabine with or without pertuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. The study population consisted of female patients, whose disease had progressed during or following previous trastuzumab therapy for metastatic disease. All patients in Arm A and Arm B received trastuzumab (8 mg/kg iv as loading dose and then 6 mg/kg iv every 3 weeks thereafter) and capecitabine oral twice daily for 14 days every 3 weeks (1250 mg/m2 twice daily in Arm A and 1000 mg/m2 twice daily in Arm B). In addition, patients in Arm B received pertuzumab (840 mg iv as loading dose and then 420 mg iv thereafter) every 3 weeks. Study treatment continued until disease progression or unacceptable toxicity.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A: Capecitabine + Trastuzumab

Group Type: ACTIVE_COMPARATOR

Capecitabine

Intervention Type: DRUG

1250 mg/m2 po twice daily for 14 days every 3 weeks

Trastuzumab

Intervention Type: DRUG

8 mg/kg iv loading, then 6 mg/kg iv every 3 weeks

B: Capecitabine + Trastuzumab + Pertuzumab

Group Type: EXPERIMENTAL

Capecitabine

Intervention Type: DRUG

1000 mg/m2 po twice daily for 14 days every 3 weeks

Pertuzumab

Intervention Type: DRUG

840 mg iv loading, then 420 mg iv every 3 weeks

Trastuzumab

Intervention Type: DRUG

8 mg/kg iv loading, then 6 mg/kg iv every 3 weeks

Interventions

Capecitabine

1000 mg/m2 po twice daily for 14 days every 3 weeks

Intervention Type: DRUG

Capecitabine

1250 mg/m2 po twice daily for 14 days every 3 weeks

Intervention Type: DRUG

Pertuzumab

840 mg iv loading, then 420 mg iv every 3 weeks

Intervention Type: DRUG

Trastuzumab

8 mg/kg iv loading, then 6 mg/kg iv every 3 weeks

Intervention Type: DRUG

Other Intervention Names

Xeloda; Xeloda; Perjeta; Herceptin

Eligibility Criteria

Inclusion Criteria

• Adult female patients >/=18 years of age
• Metastatic HER2 positive breast cancer
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Disease progression during or following trastuzumab-based therapy for 1st line metastatic breast cancer (trastuzumab must have been part of the last prior treatment regimen)
• Prior treatment with taxane-containing regimen
• Left ventricular ejection fraction (LVEF) >/=50 percent
• For women of childbearing potential agreement to use highly effective non-hormonal form of contraception or two effective forms of non-hormonal contraception by patient and/or partner. Contraception must continue for duration of study treatment and for at least 6 months after last dose of study drug treatment

Exclusion Criteria

• Prior treatment with pertuzumab or capecitabine
• Concurrent treatment with other experimental drug
• Concurrent immunotherapy or anticancer hormonal therapy
• Serious concurrent disease (e.g. active infection, uncontrolled hypertension, cardiovascular disease)
• Central nervous system (CNS) metastases, which are not well controlled
• History of exposure to anthracycline cumulative dose equivalent to 360mg/m2
• History of congestive heart failure of any New York Heart Association criteria, or serious cardiac arrhythmia requiring treatment
• History of myocardial infarction within 6 months prior to randomization
• History of LVEF decline to below 50% during or after prior trastuzumab therapy or other cardiac toxicity during previous trastuzumab treatment that necessitated discontinuation of trastuzumab
• History of another cancer which could affect compliance or result interpretation
• Inadequate organ function
• Pregnant or breastfeeding women
• life expectancy < 12 weeks

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Fundación Investigar

Buenos Aires, , Argentina

Hospital Britanico; Oncologia

Buenos Aires, , Argentina

Instituto FIDES

La Plata, , Argentina

Instituto de Investigaciones Clínicas Quilmes

Quilmes, , Argentina

Instituto de Oncología de Rosario

Rosario, , Argentina

ISIS Clinica Especializada

Santa Fe, , Argentina

A.Ö. Landesschwerpunktkrankenhaus Krems; Abtl. F. Innere Med.

Krems, , Austria

Landeskrankenhaus Rankweil; Interne E

Rankweil, , Austria

Lkh Salzburg - Univ. Klinikum Salzburg; Iii. Medizinische Abt.

Salzburg, , Austria

Medizinische Universität Wien; Univ.Klinik für Innere Medizin I - Abt. für Onkologie

Vienna, , Austria

Imeldaziekenhuis

Bonheiden, , Belgium

AZ KLINA

Brasschaat, , Belgium

UZ Brussel

Brussels, , Belgium

GHdC Site Notre Dame

Charleroi, , Belgium

CH Jolimont - Lobbes (Jolimont)

Haine-Saint-Paul, , Belgium

Jessa Zkh (Campus Virga Jesse)

Hasselt, , Belgium

AZ Groeninge

Kortrijk, , Belgium

CHU Sart-Tilman

Liège, , Belgium

Clinique Saint-Joseph

Liège, , Belgium

Clinique Ste-Elisabeth

Namur, , Belgium

AZ Nikolaas (Lodewijk)

Sint-Niklaas, , Belgium

Oncologia Sul Capixaba Servicos Medicos - Oncosul

Cachoeiro de Itapemirim, Espírito Santo, Brazil

Hospital Sao Lucas - PUCRS

Porto Alegre, Rio Grande do Sul, Brazil

Hospital Perola Byington

São Paulo, São Paulo, Brazil

Hospital A. C. Camargo; Oncologia

São Paulo, São Paulo, Brazil

Centro Oncológico de Mogi das Cruzes

São Paulo- SP, São Paulo, Brazil

Durham Regional Cancer Centre

Oshawa, Ontario, Canada

Humber River Hospital

Toronto, Ontario, Canada

University Health Network; Princess Margaret Hospital; Medical Oncology Dept

Toronto, Ontario, Canada

Uni Hospital For Tumours; Dept of Medical Oncology

Zagreb, , Croatia

Masarykuv onkologicky ustav; Oncology II

Brno, , Czechia

University Hospital; Oncology and Radiotherapy

Hradec Králové, , Czechia

Fakultni Poliklinika Vseobecne Fakultni Niemocnice; Onkologicka Klinika

Prague, , Czechia

Lekarske Fakulty Univerzity Karlovy Fakultni Nemocnice Na Bulovce; Ustav Radiacni Onkologie

Prague, , Czechia

North Estonia Medical Centre Foundation; Oncology Centre

Tallinn, , Estonia

Tartu University Hospital; Clinic of Hematology and Oncology

Tartu, , Estonia

C.H. Du Pays D'aix En Provence Service du Dr Blanc

Aix-en-Provence, , France

Centre Oncologie Du Pays Basque

Bayonne, , France

Centre Hospitalier Fleyriat; Oncologie/Hematologie

Bourg-en-Bresse, , France

CHU Henri Mondor; Service d'Oncologie Medicale

Créteil, , France

Centre Georges Francois Leclerc; Oncologie 3

Dijon, , France

Centre Leon Berard; Oncologie Genetique

Lyon, , France

Centre Antoine Lacassagne; Hopital De Jour A2

Nice, , France

Institut Curie; Oncologie Medicale

Paris, , France

Hopital Saint Antoine; Sce Oncologie

Paris, , France

Institut Jean Godinot; Oncologie Medicale

Reims, , France

Centre Henri Becquerel; Oncologie Medicale

Rouen, , France

Centre Rene Huguenin; CONSULT SPECIALISEES

Saint-Cloud, , France

Hopital Hautepierre; Hematologie Oncologie

Strasbourg, , France

Institut Claudius Regaud; Departement Oncologie Medicale

Toulouse, , France

Clinique Pasteur; Oncologie Medicale

Toulouse, , France

CAMPUS CHARITÉ MITTE; Tagesklinik für Onkologie u.Hämatologie

Berlin, , Germany

Klinikum Sindelfinden Boblingen

Böblingen, , Germany

Klinikum Bremen-Mitte gGmbH; Frauenklinik

Bremen, , Germany

St. Elisabeth Krankenhaus Köln GmbH; Gynäkologie und Geburtshilfe

Cologne, , Germany

Klinikum Darmstadt GmbH; Med. Klinik V; Onkologie & Hämatologie

Darmstadt, , Germany

Klinikum Dortmund gGmbH Klinikzentrum Mitte

Dortmund, , Germany

Universitätsklinikum Essen; Zentrum Für Frauenheilkunde

Essen, , Germany

Klinikum Frankfurt Höchst GmbH; Klinik für Gynäkologie und Geburtshilfe

Frankfurt, , Germany

Klinik Fulda, Medizinisches Versorgungszentrum Osthessen GmbH

Fulda, , Germany

Universitätsklinikum Hamburg-Eppendorf; Zentrum für operative Medizin Klinik für Gynäkologie

Hamburg, , Germany

HOPA MVZ GmbH

Hamburg, , Germany

Diakovere Henriettenstift, Frauenklinik

Hanover, , Germany

Medizinische Hochschule Zentrum Frauenheilkunde Abt.Gynäkologische Onkologie

Hanover, , Germany

ViDia Christliche Kliniken Karlsruhe, Vincentius-Diakonissen-Kliniken gAG; Frauenklinik

Karlsruhe, , Germany

Systemedic Frauenarzte Pruener Gang

Kiel, , Germany

Institut für Versorgungsforschung in der Onkologie GbR Koblenz

Koblenz, , Germany

Universitätsklinikum Schleswig-Holstein / Campus Lübeck; Klinik für Frauenheilkunde und Geburtshilfe

Lübeck, , Germany

St. Vincenz-Elisabeth-Hospital; Katholisches Klinikum Mainz

Mainz, , Germany

Klinikum rechts der Isar der TU München; Frauenklinik & Poliklinik

München, , Germany

Universitätsklinikum Münster; Klinik für Frauenheilkunde und Geburtshilfe

Münster, , Germany

St. Josefs Klinik; Medizinische Klinik

Offenburg, , Germany

Praxis für Onkologie und Hämatologie

Recklinghausen, , Germany

Johanniter Klinik

Stendal, , Germany

Klinikum Mutterhaus der Borromaeerinnen gGmbH; Haematologie/Onkologie

Trier, , Germany

GRN Klinik Weinheim

Weinheim, , Germany

Queen Mary Hospital; Surgery

Hong Kong, , Hong Kong

Queen Elizabeth Hospital; Clinical Oncology

Hong Kong, , Hong Kong

Tuen Mun Hospital; Clinical Oncology

Hong Kong, , Hong Kong

Ogyi, Orszagos Gyogyszereszeti Intezet

Budapest, , Hungary

Semmelweis Egyetem Onkologiai Központ

Budapest, , Hungary

Fövárosi Önkormányzat Bajcsy-Zsilinszky Kórház; Onkológiai Osztály

Budapest, , Hungary

Orszagos Onkologiai Intezet; B Belgyogyaszati Osztaly

Budapest, , Hungary

Semmelweis Egyetem Aok; Iii.Sz. Belgyogyaszati Klinika

Budapest, , Hungary

Municipal Hospital of Uzsoki Utca; Centre of Oncoradiology

Budapest, , Hungary

Hospital of Aladar Petz; Dept of Oncoradiology

Győr, , Hungary

Békés Megyei Pándy Kálmán Kórház; Onkologiai tanszek

Gyula, , Hungary

Kaposi Mor County Hospital; Dept. of Oncology

Kaposvár, , Hungary

Borsod-Abauj-Zemplen Megyei Korhaz Es Egyetemi Oktato Korhaz; Onkologiai Osztaly

Miskolc, , Hungary

Josa Andras Korhaz; Dept of Oncoradiology

Nyíregyháza, , Hungary

Pécsi Tudományegyetem Áok; Onkoterapias Intezet

Pécs, , Hungary

Szegedi Tudomanyegyetem, AOK, Szent-Gyorgyi Albert Klinikai Kozpont, Onkoterapias Klinika

Szeged, , Hungary

Fejér Megyei Szent György Kórház; Onkológiai Osztály

Székesfehérvár, , Hungary

Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház; Onkológiai Osztály

Szolnok, , Hungary

Istituto Tumori Fondazione Pascale; Endocrinologia Oncologica

Napoli, Campania, Italy

Az. Osp. S. Orsola Malpighi; Istituto Di Oncologia Seragnoli

Bologna, Emilia-Romagna, Italy

Ospedale Cervesi di Cattolica ; Unità Operativa di Oncologia ed Oncoematologia

Cattalica, Emilia-Romagna, Italy

AUSL Cesena; Servizio di Oncologia

Cesena, Emilia-Romagna, Italy

Ausl Ravenna-Osp.Infermi; Day Hospital Oncologia Medica

Faenza, Emilia-Romagna, Italy

Ospedale Umberto I ASL di Ravenna Presidio Ospedaliero di Lugo

Lugo, Emilia-Romagna, Italy

Azienda USL di Ravenna; Unità Operativa di Oncologia Medica

Ravenna, Emilia-Romagna, Italy

Ospedale Infermi Di Rimini; Unità Operativa di Oncologia e Oncoematologia

Rimini, Emilia-Romagna, Italy

Istituto Regina Elena; Oncologia Medica A

Rome, Lazio, Italy

Uni Cattolica Policlinico Gemelli; Oncologia Medica Ist. Medicina Interna

Rome, Lazio, Italy

Asst Papa Giovanni XXIII; Oncologia Medica

Bergamo, Lombardy, Italy

ASST DI CREMONA; Dipartimento Aziendale Oncologico

Cremona, Lombardy, Italy

Ospedale Mater Salutis; Dept of Oncology

Legnago, Lombardy, Italy

ASST DI MONZA; Oncologia Medica

Monza, Lombardy, Italy

IRCCS Fondazione Maugeri; Oncologia Medica II

Pavia, Lombardy, Italy

ASST LARIANA; Oncologia

S. Fermo Della Battaglia (CO), Lombardy, Italy

A.O. Città della Salute e della Scienza - Presidio Molinette; divisione oncologia medica

Turin, Piedmont, Italy

Ospedale Civile; Oncologia Medica

Sassari, Sardinia, Italy

ARNAS-Ospedale Civico Maurizio Ascoli; Unità Operativa di Oncologia Medica

Palermo, Sicily, Italy

Azienda ospedaliero-universitaria careggi, Sezione di radioterapia del dipartimento di fisiopatolo

Florence, Tuscany, Italy

A.O. Universitaria Pisana; Oncologia

Pisa, Tuscany, Italy

Oaxaca Site Management Organization

Oaxaca City, , Mexico

Centro Oncológico Estatal; ISSSEMYM Oncología

Toluca, , Mexico

Vu Medisch Centrum; Afdeling Maag-, Darm- En Leverziekte

Amsterdam, , Netherlands

Hospital Nacional Carlos Alberto Seguin Escobedo-Essalud; Oncology & Haemathology

Arequipa, , Peru

Hospital Nacional Edgardo Rebagliati Martins

Jesus Maria, , Peru

Clinica Anglo Americana - Centro de Investigacion Oncologia CAA

Lima, , Peru

Unidad de Investigacion Oncologia Clinica - Piura; Unidad de Oncología Clínica

Piura, , Peru

Szpital Specjalistyczny Podkarpacki Ośrodek Onkologiczny

Brzozów, , Poland

Wojewodzki Szpital Zespolony; Oddzial Chemioterapii

Elblag, , Poland

Wojewodzkie Centrum Onkologii

Gdansk, , Poland

COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej

Lublin, , Poland

Wojewodzki Sziptal Specjalistyczny Im. Janusza Korczaka; Oddzial Onkologiczny, Oddzial Chemioterapii

Słupsk, , Poland

Spitalul Clinic Sf. Maria; Departmental De Oncologie

Bucharest, , Romania

Institut of Oncology Al. Trestioreanu Bucharest; Oncology Department

Bucharest, , Romania

Institute Of Oncology Bucharest; Medical Oncology

Bucharest, , Romania

Cluj Clinical County Hospital; Oncology Dept

Cluj-Napoca, , Romania

Prof. Dr. I. Chiricuta Institute of Oncology

Cluj-Napoca, , Romania

Medisprof SRL

Cluj-Napoca, , Romania

Municipal Clinical Hospital Filantropia; Oncology

Craiova, , Romania

Euroclinic Center of Oncology SRL

Iași, , Romania

Regional Oncology Hospital of Krasnodar; Oncology

Krasnodar, , Russia

Blokhin Cancer Research Center; Combined Treatment

Moscow, , Russia

Semashko Central Clinical Hospital; Dept of Chemotherapy

Moscow, , Russia

GUZ Perm Region Oncology Dispensary

Perm, , Russia

S.-Peterburg Pavlov State Medical University ; Haematology

Saint Petersburg, , Russia

Saint-Petersburg City Clinical Oncology Dispensary

Saint Petersburg, , Russia

SBI of Healthcare of Stavropol region Stavropol Regional Clinical Oncology Dispensary

Stavropol, , Russia

Severance Hospital

Seoul, , South Korea

Seoul National University Hosp; Dept Internal Med Hem Onc

Seoul, , South Korea

Asan Medical Center, Uni Ulsan Collegemedicine; Dept.Internal Medicine / Divisionhematology/Oncology

Seoul, , South Korea

Korea University Guro Hospital; Oncology

Seoul, , South Korea

Hospital Clinica Benidorm

Benidorm, Alicante, Spain

Complejo Hospitalario Torrecardenas; Servicio de Oncologia

Almería, Almeria, Spain

Consorci Hospitalari de Terrassa

Terrassa, Barcelona, Spain

Hospital Provincial de Castellón

Castellon, Castellon, Spain

Fundacion Hospital de Alcorcon; Servicio de Oncologia

Alcorcón, Madrid, Spain

Hospital Universitario Puerta de Hierro

Majadahonda, Madrid, Spain

Hospital Universitario de Canarias;servicio de Oncologia

San Cristóbal de La Laguna, Tenerife, Spain

Complejo Hospitalario Nuestra Señora de la Candelaria; Servicio de Oncologia

Santa Cruz de Tenerife, Tenerife, Spain

Hospital de Sagunto; Servicio de Oncologia

Sagunto, Valencia, Spain

Hospital de Basurto; Servicio de Oncologia

Bilbao, Vizcaya, Spain

Hospital Clinic i Provincial; Servicio de Farmacia

Barcelona, , Spain

Institut Catala d Oncologia Hospital Duran i Reynals

Barcelona, , Spain

Hospital Juan Ramon Jimenez;Servicio de Oncologia

Huelva, , Spain

Complejo Asistencial Universitario de Leon; Servicio de Oncologia

León, , Spain

Hospital General Universitario Gregorio Marañon; Servicio de Oncologia

Madrid, , Spain

Hospital Ruber Internacional;Servicio de Oncologia

Madrid, , Spain

Fundacion Jimenez Diaz; Servicio de Oncologia

Madrid, , Spain

Hospital La Paz

Madrid, , Spain

Complejo Hospitalario de Pontevedra; Servicio de Oncologia

Pontevedra, , Spain

Hospital Clinico Universitario de Salamanca; Servicio de Oncologia

Salamanca, , Spain

Hospital Universitario Virgen Macarena; Servicio de Oncologia

Seville, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

Hospital Univ. Nuestra Señora de Valme;

Seville, , Spain

Hospital Sant Pau i Santa Tecla

Tarragona, , Spain

Complejo Hospitalario de Toledo- H. Virgen de la Salud; Servicio de Oncologia

Toledo, , Spain

Instituto Valenciano Oncologia; Oncologia Medica

Valencia, , Spain

Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

Valencia, , Spain

Hospital Universitario la Fe; Servicio de Oncologia

Valencia, , Spain

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Phramongkutklao Hospital;Dept Surgery/Surgical Oncology Unit

Bangkok, , Thailand

Ramathibodi Hospital; Department of Surgery/Breast and Endocrine Unit

Bangkok, , Thailand

Maharaj Nakorn Chiang Mai Hospital; Department of Surgery/Head Neck and Breast Unit; Clinical Trial

Chiang Mai, , Thailand

Srinagarind Hospital; Department of Surgery

Khon Kaen, , Thailand

Songklanagarind Hospital; Department of Surgery

Songkhla, , Thailand

Royal Bournemouth General Hospital; Oncology

Bournemouth, , United Kingdom

Velindre Cancer Centre; Oncology Dept

Cardiff, , United Kingdom

Broomfield Hospital

Chelmsford, , United Kingdom

University Hospital of North Durham; Oncology

Durham, , United Kingdom

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Christie Hospital; Breast Cancer Research Office

Manchester, , United Kingdom

Nottingham City Hospital

Nottingham, , United Kingdom

Peterborough City Hospital, Edith Cavell Campus; Oncology Department

Peterborough, , United Kingdom

Great Western Hospital; Clinical Oncology

Swindon, , United Kingdom

Royal Cornwall Hospital; Dept of Clinical Oncology

Truro, , United Kingdom

Countries

Argentina; Austria; Belgium; Brazil; Canada; Croatia; Czechia; Estonia; France; Germany; Hong Kong; Hungary; Italy; Mexico; Netherlands; Peru; Poland; Romania; Russia; South Korea; Spain; Thailand; United Kingdom

Other Identifiers

2008-006801-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MO22324

Identifier Type: -

Identifier Source: org_study_id