Phase IIIb Study to Evaluate the Safety and Tolerability of Herceptin SC With Perjeta and Docetaxel in Patients With HER2-positive Advanced Breast Cancer

Breast Cancer Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02402712
• Other study ID #: BO29159
• Secondary ID: 2014-001458-40
• Status: Completed
• Phase: Phase 3
• Start date: May 6, 2015
• Est. completion date: February 22, 2019

Study information

• Verified date: September 2019
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 418
• Est. completion date: February 22, 2019
• Est. primary completion date: February 22, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Docetaxel
Intravenous administration according to local label/clinical practice, after Herceptin and Perjeta.
• pertuzumab [Perjeta]
Intravenous infusion every 3 weeks. First dose: 840 mg. Subsequent doses: 420 mg
• trastuzumab [Herceptin]
Subcutaneous administration of 600 mg/5 mL every 3 weeks

Locations

Country	Name	City	State
Belgium	AZ Sint Jan	Brugge
Belgium	UZ Brussel	Brussel
Belgium	Cliniques Universitaires St-Luc	Bruxelles
Belgium	CHU Sart-Tilman	Liège
Belgium	Clinique Saint-Joseph	Liège
Belgium	Sint Augustinus Wilrijk	Wilrijk
Bulgaria	Multiprofile Hospital For Active Treatment Dr. Tota Venkova JSC	Gabrovo
Bulgaria	Comprehensive Cancer Center-Plovdiv	Plovdiv
Bulgaria	Multiprofile Hospital for Active Treatment Central Onco Hospital OOD	Plovdiv
Bulgaria	University Multiprofile Hospital for Active Treatment Sveti Georgi EAD	Plovdiv
Bulgaria	Specialized Hospital for Active Treatment of Oncological Diseases - Sofia District EOOD	Sofia
Bulgaria	Specialized Hospital for Active Cancer Treatment, Dr. Mark Antonov Markov - Varna Ltd	Varna
Bulgaria	MDOZS Vrasta Ltd.	Vratsa
Canada	Royal Victoria Regional Health Centre	Barrie	Ontario
Canada	Moncton Hospital	Moncton	New Brunswick
France	Centre Hospitalier Regional Metz-Thionville - Hopital de Mercy	Ars-Laquenexy
France	Medipole De Savoie; Departement Oncologie	Challes Les Eaux
France	Hopital Prive Sainte Marie	Chalon sur Saone
France	Centre Hospitalier Louis Pasteur	Chartes Le Coudray
France	Pole Sante Republique; Pharmacie Oncologique	Clermont Ferrand
France	Centre Georges Francois Leclerc	Dijon
France	CHU de Grenoble	Grenoble
France	Groupe Hospitalier Mutualiste de Grenoble	Grenoble Cedex
France	Hopital Europeen	Marseille
France	Centre Hospitalier de Mont de Marsan - Hopital Layne	Mont De Marsan
France	Hopital Saint Joseph; Service de Rhumatologie	Paris
France	Centre Hospitalier Lyon Sud	Pierre Benite
France	Strasbourg Oncologie Libérale	Strasbourg
France	Gustave Roussy	Villejuif CEDEX
Germany	Studienzentrum Aschaffenburg	Aschaffenburg
Germany	Onkologische Schwerpunktpraxis Dr. Joerg Schilling	Berlin
Germany	Universitaetsklinikum Erlangen	Erlangen
Germany	Kliniken Essen-Mitte	Essen
Germany	Universitätsklinikum Essen	Essen
Germany	Praxis für Interdisziplinäre Onkologie und Hämatologie GbR	Freiburg
Germany	Universitatsklinikum Schleswig-Holstein; Klinik fuer Innere Medizin I	Lubeck
Germany	Onkologische Schwerpunktpraxis Lübeck	Lübeck
Germany	Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz	Mainz
Germany	Suedharz Klinikum Nordhausen gGmbH	Nordhausen
Germany	Sana Klinikum Offenbach GmbH; Klinik für Gynäkologie & Geburtshilfe	Offenbach
Germany	Johanniter-Krankenhaus Genthin - Stendal GmbH; Gynäkologie und gynäkologische Onkologie	Stendal
Germany	Klinikum Mutterhaus der Borromaeerinnen	Trier
Germany	Universitätsklinikum Würzburg	Wuerzburg
Hungary	Magyar Honvedseg Egeszsegugyi Kozpont; Fázis I-es Klinikai Farmakológiai Vizsgálóhely	Budapest
Hungary	Ogyi, Orszagos Gyogyszereszeti Intezet	Budapest
Hungary	Orszagos Onkologiai Intezet	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	Szent Imre Egyetemi Oktatokorhaz	Budapest
Hungary	Szent Margit Hospital; Dept. of Oncology	Budapest
Hungary	Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Oktatókórház	Miskolc
Italy	Ospedale Santa Maria Annunziata	Bagno A Ripoli	Toscana
Italy	Asst Papa Giovanni XXIII	Bergamo	Lombardia
Italy	Azienda Ospedaliero - Universitaria Policlinico - Vittorio Emanuele	Catania	Sicilia
Italy	Azienda Ospedaliero-Universitaria di Ferrara, Arcispedale Sant'Anna	Cona (Ferrara)	Veneto
Italy	Azienda Ospedaliera Universitaria Careggi	Firenze	Toscana
Italy	Ospedale Policlinico San Martino	Genova	Liguria
Italy	Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori	Meldola	Emilia-Romagna
Italy	Istituto Europeo Di Oncologia	Milano	Lombardia
Italy	Azienda Ospedaliero - Universitaria di Modena Policlinico	Modena	Emilia-Romagna
Italy	Ospedale Sacro Cuore Don Calabria	Negrar	Veneto
Italy	IOV - Istituto Oncologico Veneto IRCCS	Padova	Veneto
Italy	Azienda USL 5 di Pisa	Pisa	Toscana
Italy	Azienda Ospedaliera Regionale San Carlo	Potenza	Basilicata
Italy	Ospedale Santo Stefano, Azienda USL Centro Prato	Prato	Toscana
Italy	Azienda Ospedaliera di Reggio Emilia - Arcispedale Santa Maria Nuova	Reggio Emilia	Emilia-Romagna
Italy	Ospedale Infermi di Rimini	Rimini	Emilia-Romagna
Italy	Istituti Fisioterapici Ospitalieri	Roma	Lazio
Italy	Istituto Clinico Humanitas	Rozzano (MI)	Lombardia
Italy	Asst Della Valtellina E Dell'Alto Lario	Sondrio	Lombardia
Italy	Azienda Ospedaliera Santa Maria di Terni	Terni	Umbria
Italy	"Azienda Ospedaliera Universitaria Integrata Verona Ospedale Borgo Trento"	Verona	Veneto
Mexico	Grupo Medico Camino	DF
Mexico	Consultorio de Medicina Especializada	Mexico	Mexico CITY (federal District)
Mexico	Fundacion de Cancer de Mama.A.C.	Mexico
Mexico	Superare Centro de Infusion S.A. de C.V.	Mexico
Mexico	Centro Medico San Jose	Monterrey, Nuevo Leon
Mexico	Cancerología	Queretaro
Poland	Bialostockie Centrum Onkologii im. Marii Sklodowskiej - Curie	Bialystok
Poland	Copernicus Podmiot Medyczny Sp. z o.o. Wojewodzkie Centrum Onkologii	Gdansk
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Szpitale Pomorskie Sp. z o. o.	Gdynia
Poland	Przychodnia Lekarska KOMED	Konin
Poland	Szpital Uniwersytecki w Krakowie	Krakow
Poland	Centrum Onkologii Ziemi Lubelskiej im. sw. Jana z Dukli	Lublin
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej MSW z W-MCO w Olsztynie	Olsztyn
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej Opolskie Centrum Onkologii	Opole
Poland	Szpital Kliniczny; Przemienienia Panskiego;Uniwersytetu Medyczny im.; Karola Marcinkowskiego w Pozna	Poznan
Poland	Wielkopolskie Centrum Onkologii	Poznan
Poland	Centrum Onkologii - Instytut im. Marii Sklodowskiej-Curie; Klinika Onkologiczna	Warsaw
Poland	MAGODENT Sp. z o.o.	Warsaw
Portugal	Hospital de Braga	Braga
Portugal	Instituto Portugues Oncologia de Coimbra Francisco Gentil, EPE	Coimbra
Portugal	Centro Hospitalar de Lisboa Norte, EPE - Hospital Santa Maria	Lisboa
Portugal	Hospital da Luz	Lisboa
Portugal	IPO do Porto; Servico de Oncologia Medica	Porto
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario Reina Sofia	Cordoba
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario Puerta de Hierro - Majadahonda	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Complexo Hospitalario Universitario de Santiago (CHUS) - Hospital Clinico Universitario	Santiago de Compostela	LA Coruña
Spain	Fundacion Instituto Valenciano de Oncologia (IVO)	Valencia
United Kingdom	Betsi Cadwaladr University Health Board	Bangor Gwynedd
United Kingdom	Velindre Cancer Centre	Cardiff
United Kingdom	Dorset County Hospital	Dorchester
United Kingdom	University Hospitals of Leicester NHS Trust - Leicester Royal Infirmary	Leicester
United Kingdom	Guys and St Thomas NHS Foundation Trust, Guys Hospital	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Mount Vernon Cancer Centre	Northwood
United Kingdom	Peterborough City Hospital	Peterborough
United Kingdom	Portsmouth Hospitals NHS Trust - Queen Alexandra Hospital	Portsmouth
United Kingdom	Royal Cornwall Hospitals NHS Trust	Truro

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Belgium,  Bulgaria,  Canada,  France,  Germany,  Hungary,  Italy,  Mexico,  Poland,  Portugal,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse events (AEs)		Up to 24 months after the last patient has been enrolled, approximately 3.5 years
Primary	Incidence and severity of adverse events Grade >/= 3, according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0		Up to 24 months after the last patient has been enrolled, approximately 3.5 years
Primary	Incidence of cardiac events (composite outcome measure): congestive heart failure (CHF) and cardiac death		Up to 24 months after the last patient has been enrolled, approximately 3.5 years
Secondary	Progression-free survival, tumor assessments according to RECIST v1.1		Up to 3.5 years
Secondary	Overall survival		Up to 3.5 years
Secondary	Objective response rate, defined as a complete response (CR) or a partial response (PR)		Up to 3.5 years
Secondary	Incidence of anti-Herceptin, anti-rHuPH20 antibodies		Up to 3.5 years