Clinical trial NCT02402712: Phase IIIb Study to Evaluate the Safety and Tolerability of Herceptin SC With Perjeta and Docetaxel in Patients With HER2-positive Advanced Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2015-03-30
Enrollment: 418
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label, single-arm, multicenter, Phase IIIb study to evaluate the safety and tolerability of Herceptin SC in combination with Perjeta IV plus docetaxel in female patients with HER2-positive metastatic or locally recurrent breast cancer. Enrolled patients are to receive study medication until disease progression, unacceptable toxicity, withdrawal of consent, death, or predefined study end, whichever occurs first. The anticipated time on study treatment is approximately 24 months. The target sample size is 400.


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed and documented adenocarcinoma of the breast with metastatic or locally recurrent disease not amenable to curative resection. Patients with measurable and/or non-measurable disease evaluable according to Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 are eligible.
* HER2-positive disease (defined as either immunohistochemistry \[IHC\] 3 + or in situ hybridization \[ISH\] positive) as assessed by local laboratory on primary tumor or metastatic site if primary tumor not available
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
* Left ventricular ejection fraction (LVEF) of at least 50%
* Negative serum pregnancy test result at baseline and use of effective contraception as defined by the protocol

Exclusion Criteria:

* Previous systemic non-hormonal anti-cancer therapy for the metastatic or locally recurrent disease. Note: Prior to study entry, up to two lines of hormonal therapy for metastatic or locally recurrent disease are permitted, one of which may be in combination with everolimus.
* Disease-free interval of less than 6 months from completion of adjuvant or neoadjuvant systemic non-hormonal treatment to recurrence of breast cancer
* Previous approved or investigative anti-HER2 agents as neoadjuvant or adjuvant therapy for any breast cancer treatment, except Herceptin
* History of persistent Grade 2 or higher hematological toxicity resulting from previous adjuvant or neoadjuvant therapy
* Radiographic evidence of central nervous system (CNS) metastases as assessed by computed tomography (CT) or magnetic resonance imaging (MRI), unless they have been treated and have been stable for at least 3 months and do not require ongoing corticosteroid treatment
* Current peripheral neuropathy of Grade 3 or greater
* History of other malignancy within the last 5 years prior to first dose of study drug administration, except for carcinoma in situ of the cervix or basal cell carcinoma
* Inadequate organ function
* Uncontrolled hypertension with or without medication
* Clinically significant cardiovascular disease
* History of LVEF decline to below 50% during or after prior Herceptin neo-adjuvant or adjuvant therapy
* Current known infection with HIV, hepatitis B virus, or hepatitis C virus
* Severe uncontrolled concomitant disease that would contraindicate the use of any of the investigational drugs used in this study or that would put the patient at high risk for treatment-related complications, including severe pulmonary conditions/illness
* Pregnant or lactating women
* Dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy
* History of receiving any investigational treatment within 28 days prior to first dose of study drug administration (dosing) or concurrent participation in any interventional clinical trial

Primary outcomes:
measure: Incidence of adverse events (AEs)
timeFrame: Up to 24 months after the last patient has been enrolled, approximately 3.5 years
measure: Incidence and severity of adverse events Grade >/= 3, according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0
timeFrame: Up to 24 months after the last patient has been enrolled, approximately 3.5 years
measure: Incidence of cardiac events (composite outcome measure): congestive heart failure (CHF) and cardiac death
timeFrame: Up to 24 months after the last patient has been enrolled, approximately 3.5 years
Secondary outcomes:
measure: Progression-free survival, tumor assessments according to RECIST v1.1
timeFrame: Up to 3.5 years
measure: Overall survival
timeFrame: Up to 3.5 years
measure: Objective response rate, defined as a complete response (CR) or a partial response (PR)
timeFrame: Up to 3.5 years
measure: Incidence of anti-Herceptin, anti-rHuPH20 antibodies
timeFrame: Up to 3.5 years
Other outcomes:
Locations:
city: Brugge
country: Belgium
facility: AZ Sint Jan
city: Brussel
country: Belgium
facility: UZ Brussel
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires St-Luc
city: Liège
country: Belgium
facility: CHU Sart-Tilman
city: Liège
country: Belgium
facility: Clinique Saint-Joseph
city: Wilrijk
country: Belgium
facility: Sint Augustinus Wilrijk
city: Gabrovo
country: Bulgaria
facility: Multiprofile Hospital For Active Treatment Dr. Tota Venkova JSC
city: Plovdiv
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Central Onco Hospital OOD
city: Plovdiv
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Sveti Georgi EAD
city: Plovdiv
country: Bulgaria
facility: Comprehensive Cancer Center-Plovdiv
city: Sofia
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Oncological Diseases - Sofia District EOOD
city: Varna
country: Bulgaria
facility: Specialized Hospital for Active Cancer Treatment, Dr. Mark Antonov Markov - Varna Ltd
city: Vratsa
country: Bulgaria
facility: MDOZS Vrasta Ltd.
city: Moncton
country: Canada
facility: Moncton Hospital
state: New Brunswick
city: Barrie
country: Canada
facility: Royal Victoria Regional Health Centre
state: Ontario
city: Ars-Laquenexy
country: France
facility: Centre Hospitalier Regional Metz-Thionville - Hopital de Mercy
city: Challes Les Eaux
country: France
facility: Medipole De Savoie; Departement Oncologie
city: Chalon sur Saone
country: France
facility: Hopital Prive Sainte Marie
city: Chartes Le Coudray
country: France
facility: Centre Hospitalier Louis Pasteur
city: Clermont Ferrand
country: France
facility: Pole Sante Republique; Pharmacie Oncologique
city: Dijon
country: France
facility: Centre Georges Francois Leclerc
city: Grenoble Cedex
country: France
facility: Groupe Hospitalier Mutualiste de Grenoble
city: Grenoble
country: France
facility: CHU de Grenoble
city: Marseille
country: France
facility: Hopital Europeen
city: Mont De Marsan
country: France
facility: Centre Hospitalier de Mont de Marsan - Hopital Layne
city: Paris
country: France
facility: Hopital Saint Joseph; Service de Rhumatologie
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud
city: Strasbourg
country: France
facility: Strasbourg Oncologie Libérale
city: Villejuif CEDEX
country: France
facility: Gustave Roussy
city: Aschaffenburg
country: Germany
facility: Studienzentrum Aschaffenburg
city: Berlin
country: Germany
facility: Onkologische Schwerpunktpraxis Dr. Joerg Schilling
city: Erlangen
country: Germany
facility: Universitaetsklinikum Erlangen
city: Essen
country: Germany
facility: Kliniken Essen-Mitte
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Freiburg
country: Germany
facility: Praxis für Interdisziplinäre Onkologie und Hämatologie GbR
city: Lubeck
country: Germany
facility: Universitatsklinikum Schleswig-Holstein; Klinik fuer Innere Medizin I
city: Lübeck
country: Germany
facility: Onkologische Schwerpunktpraxis Lübeck
city: Mainz
country: Germany
facility: Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
city: Nordhausen
country: Germany
facility: Suedharz Klinikum Nordhausen gGmbH
city: Offenbach
country: Germany
facility: Sana Klinikum Offenbach GmbH; Klinik für Gynäkologie & Geburtshilfe
city: Stendal
country: Germany
facility: Johanniter-Krankenhaus Genthin - Stendal GmbH; Gynäkologie und gynäkologische Onkologie
city: Trier
country: Germany
facility: Klinikum Mutterhaus der Borromaeerinnen
city: Wuerzburg
country: Germany
facility: Universitätsklinikum Würzburg
city: Budapest
country: Hungary
facility: Szent Margit Hospital; Dept. of Oncology
city: Budapest
country: Hungary
facility: Ogyi, Orszagos Gyogyszereszeti Intezet
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Budapest
country: Hungary
facility: Szent Imre Egyetemi Oktatokorhaz
city: Budapest
country: Hungary
facility: Orszagos Onkologiai Intezet
city: Budapest
country: Hungary
facility: Magyar Honvedseg Egeszsegugyi Kozpont; Fázis I-es Klinikai Farmakológiai Vizsgálóhely
city: Miskolc
country: Hungary
facility: Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Oktatókórház
city: Potenza
country: Italy
facility: Azienda Ospedaliera Regionale San Carlo
state: Basilicata
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori
state: Emilia-Romagna
city: Modena
country: Italy
facility: Azienda Ospedaliero - Universitaria di Modena Policlinico
state: Emilia-Romagna
city: Reggio Emilia
country: Italy
facility: Azienda Ospedaliera di Reggio Emilia - Arcispedale Santa Maria Nuova
state: Emilia-Romagna
city: Rimini
country: Italy
facility: Ospedale Infermi di Rimini
state: Emilia-Romagna
city: Roma
country: Italy
facility: Istituti Fisioterapici Ospitalieri
state: Lazio
city: Genova
country: Italy
facility: Ospedale Policlinico San Martino
state: Liguria
city: Bergamo
country: Italy
facility: Asst Papa Giovanni XXIII
state: Lombardia
city: Milano
country: Italy
facility: Istituto Europeo Di Oncologia
state: Lombardia
city: Rozzano (MI)
country: Italy
facility: Istituto Clinico Humanitas
state: Lombardia
city: Sondrio
country: Italy
facility: Asst Della Valtellina E Dell'Alto Lario
state: Lombardia
city: Catania
country: Italy
facility: Azienda Ospedaliero - Universitaria Policlinico - Vittorio Emanuele
state: Sicilia
city: Bagno A Ripoli
country: Italy
facility: Ospedale Santa Maria Annunziata
state: Toscana
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
state: Toscana
city: Pisa
country: Italy
facility: Azienda USL 5 di Pisa
state: Toscana
city: Prato
country: Italy
facility: Ospedale Santo Stefano, Azienda USL Centro Prato
state: Toscana
city: Terni
country: Italy
facility: Azienda Ospedaliera Santa Maria di Terni
state: Umbria
city: Cona (Ferrara)
country: Italy
facility: Azienda Ospedaliero-Universitaria di Ferrara, Arcispedale Sant'Anna
state: Veneto
city: Negrar
country: Italy
facility: Ospedale Sacro Cuore Don Calabria
state: Veneto
city: Padova
country: Italy
facility: IOV - Istituto Oncologico Veneto IRCCS
state: Veneto
city: Verona
country: Italy
facility: "Azienda Ospedaliera Universitaria Integrata Verona Ospedale Borgo Trento"
state: Veneto
city: Mexico
country: Mexico
facility: Consultorio de Medicina Especializada
state: Mexico CITY (federal District)
city: DF
country: Mexico
facility: Grupo Medico Camino
city: Mexico
country: Mexico
facility: Superare Centro de Infusion S.A. de C.V.
city: Mexico
country: Mexico
facility: Fundacion de Cancer de Mama.A.C.
city: Monterrey, Nuevo Leon
country: Mexico
facility: Centro Medico San Jose
city: Queretaro
country: Mexico
facility: Cancerología
city: Bialystok
country: Poland
facility: Bialostockie Centrum Onkologii im. Marii Sklodowskiej - Curie
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Gdansk
country: Poland
facility: Copernicus Podmiot Medyczny Sp. z o.o. Wojewodzkie Centrum Onkologii
city: Gdynia
country: Poland
facility: Szpitale Pomorskie Sp. z o. o.
city: Konin
country: Poland
facility: Przychodnia Lekarska KOMED
city: Krakow
country: Poland
facility: Szpital Uniwersytecki w Krakowie
city: Lublin
country: Poland
facility: Centrum Onkologii Ziemi Lubelskiej im. św. Jana z Dukli
city: Olsztyn
country: Poland
facility: Samodzielny Publiczny Zakład Opieki Zdrowotnej MSW z W-MCO w Olsztynie
city: Opole
country: Poland
facility: Samodzielny Publiczny Zakład Opieki Zdrowotnej Opolskie Centrum Onkologii
city: Poznan
country: Poland
facility: Szpital Kliniczny; Przemienienia Panskiego;Uniwersytetu Medyczny im.; Karola Marcinkowskiego w Pozna
city: Poznan
country: Poland
facility: Wielkopolskie Centrum Onkologii
city: Warsaw
country: Poland
facility: Centrum Onkologii - Instytut im. Marii Sklodowskiej-Curie; Klinika Onkologiczna
city: Warsaw
country: Poland
facility: MAGODENT Sp. z o.o.
city: Braga
country: Portugal
facility: Hospital de Braga
city: Coimbra
country: Portugal
facility: Instituto Portugues Oncologia de Coimbra Francisco Gentil, EPE
city: Lisboa
country: Portugal
facility: Hospital da Luz
city: Lisboa
country: Portugal
facility: Centro Hospitalar de Lisboa Norte, EPE - Hospital Santa Maria
city: Porto
country: Portugal
facility: IPO do Porto; Servico de Oncologia Medica
city: Santiago de Compostela
country: Spain
facility: Complexo Hospitalario Universitario de Santiago (CHUS) - Hospital Clinico Universitario
state: LA Coruña
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro - Majadahonda
city: Valencia
country: Spain
facility: Fundacion Instituto Valenciano de Oncologia (IVO)
city: Bangor Gwynedd
country: United Kingdom
facility: Betsi Cadwaladr University Health Board
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
city: Dorchester
country: United Kingdom
facility: Dorset County Hospital
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester NHS Trust - Leicester Royal Infirmary
city: London
country: United Kingdom
facility: Guys and St Thomas NHS Foundation Trust, Guys Hospital
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre
city: Peterborough
country: United Kingdom
facility: Peterborough City Hospital
city: Portsmouth
country: United Kingdom
facility: Portsmouth Hospitals NHS Trust - Queen Alexandra Hospital
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospitals NHS Trust
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Kuemmel S, Tondini CA, Abraham J, Nowecki Z, Itrych B, Hitre E, Karaszewska B, Juarez-Ramiro A, Morales-Vasquez F, Perez-Garcia JM, Cardona-Huerta S, Monturus E, Sequi M, Restuccia E, Benyunes M, Martin M. Subcutaneous trastuzumab with pertuzumab and docetaxel in HER2-positive metastatic breast cancer: Final analysis of MetaPHER, a phase IIIb single-arm safety study. Breast Cancer Res Treat. 2021 Jun;187(2):467-476. doi: 10.1007/s10549-021-06145-3. Epub 2021 Mar 21.