A Study Evaluating Pertuzumab (Perjeta) Combined With Trastuzumab (Herceptin) and Standard Anthracycline-based Chemotherapy in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Locally Advanced, Inflammatory, or Early-stage Breast Cancer

NCT ID: NCT02132949

Last Updated: 2021-09-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 401 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-14
• Study Completion Date: 2020-08-25

Brief Summary

This multicenter, non-randomized, open-label, phase 2 study is designed to evaluate the safety and efficacy of pertuzumab (Perjeta) in combination with trastuzumab (Herceptin) and anthracycline-based chemotherapy as neoadjuvant treatment in participants with HER2-positive locally advanced, inflammatory, or early-stage breast cancer. Each investigator will choose a treatment regimen (A or B) for all of their participants to follow. Treatment regimen A (for Cohort A) will include dose-dense doxorubicin and cyclophosphamide (ddAC), followed by paclitaxel, with pertuzumab and trastuzumab given from the start of paclitaxel. Treatment regimen B (for Cohort B) will include 5-fluorouracil, epirubicin, and cyclophosphamide (FEC), followed by docetaxel, with pertuzumab and trastuzumab given from the start of docetaxel. Participants in both cohorts will subsequently undergo surgical treatment and then resume pertuzumab and trastuzumab treatment.

Conditions

Breast Cancer

Study Design

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

Study Groups

Cohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab

Participants received neoadjuvant treatment with dose-dense doxorubicin and cyclophosphamide (ddAC), with administration of doxorubicin 60 milligrams per square meter (mg/m\^2) intravenously (IV) once every 2 weeks (q2w) and cyclophosphamide 600mg/m\^2 IV q2w for 4 cycles, followed by paclitaxel 80mg/m\^2 IV once weekly (qw) for 12 weeks. Pertuzumab (840 milligrams \[mg\] IV loading dose then 420mg IV q3w) and trastuzumab (8 milligrams per kilogram \[mg/kg\] IV loading dose then 4mg/kg IV q3w) were administered along with paclitaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received adjuvant treatment with pertuzumab and trastuzumab IV q3w (up to 13 cycles), for a total of 17 cycles of pertuzumab and trastuzumab therapy during the study. Radiotherapy and adjuvant hormonal therapy were also given as clinically indicated. Following treatment completion/discontinuation, participants were followed for safety and efficacy for up to 5 years.

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

Participants will receive cyclophosphamide 600 milligrams per square meter (mg/m\^2) intravenous (IV) given on Day 1 of each cycle q2w.

Doxorubicin

Intervention Type: DRUG

Participants will receive doxorubicin 60 mg/m\^2 IV on Day 1 of each cycle q2w.

Paclitaxel

Intervention Type: DRUG

Participants will receive paclitaxel 80 mg/m\^2 IV given weekly.

Pertuzumab

Intervention Type: DRUG

Participants will receive pertuzumab at a loading dose of 840 milligrams (mg) IV loading dose, then 420 mg IV q3w.

Trastuzumab

Intervention Type: DRUG

Participants will receive trastuzumab at a loading dose of 8 milligrams per kilogram (mg/kg) IV, then 6 mg/kg IV q3w.

Cohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab

Participants received neoadjuvant treatment with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC), with administration of 5-fluorouracil 500mg/m\^2 intravenously (IV) q3w, epirubicin 100mg/m\^2 IV q3w, and cyclophosphamide 600mg/m\^2 IV q3w for 4 cycles, followed by docetaxel (with starting dose of 75mg/m\^2 in Cycle 5, then 100mg/m\^2 for Cycles 6-8) q3w for 4 cycles. Pertuzumab (840 mg IV loading dose then 420mg IV q3w) and trastuzumab (8 mg/kg IV loading dose then 4mg/kg IV q3w) were given along with doectaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received adjuvant treatment with pertuzumab and trastuzumab IV q3w (up to 13 cycles), for a total of 17 cycles of pertuzumab and trastuzumab therapy during the study. Radiotherapy and adjuvant hormonal therapy were also given as clinically indicated. Following treatment completion/discontinuation, participants were followed for safety and efficacy for up to 5 years.

Group Type: EXPERIMENTAL

5-Fluorouracil

Intervention Type: DRUG

Participants will receive 5-fluorouracil 500 mg/m\^2 IV on Day 1 of each cycle q3w.

Cyclophosphamide

Intervention Type: DRUG

Participants will receive cyclophosphamide 600 milligrams per square meter (mg/m\^2) intravenous (IV) given on Day 1 of each cycle q2w.

Docetaxel

Intervention Type: DRUG

Participants will receive docetaxel at a starting dose of 75 mg/m\^2 IV for the first cycle and the dose may be escalated to 100 mg/m\^2 for subsequent cycles q3w.

Epirubicin

Intervention Type: DRUG

Participants will receive epirubicin 100 mg/m\^2 IV on Day 1 of each cycle q3w.

Pertuzumab

Intervention Type: DRUG

Participants will receive pertuzumab at a loading dose of 840 milligrams (mg) IV loading dose, then 420 mg IV q3w.

Trastuzumab

Intervention Type: DRUG

Participants will receive trastuzumab at a loading dose of 8 milligrams per kilogram (mg/kg) IV, then 6 mg/kg IV q3w.

Interventions

5-Fluorouracil

Participants will receive 5-fluorouracil 500 mg/m\^2 IV on Day 1 of each cycle q3w.

Intervention Type: DRUG

Cyclophosphamide

Participants will receive cyclophosphamide 600 milligrams per square meter (mg/m\^2) intravenous (IV) given on Day 1 of each cycle q2w.

Intervention Type: DRUG

Docetaxel

Participants will receive docetaxel at a starting dose of 75 mg/m\^2 IV for the first cycle and the dose may be escalated to 100 mg/m\^2 for subsequent cycles q3w.

Intervention Type: DRUG

Doxorubicin

Participants will receive doxorubicin 60 mg/m\^2 IV on Day 1 of each cycle q2w.

Intervention Type: DRUG

Epirubicin

Participants will receive epirubicin 100 mg/m\^2 IV on Day 1 of each cycle q3w.

Intervention Type: DRUG

Paclitaxel

Participants will receive paclitaxel 80 mg/m\^2 IV given weekly.

Intervention Type: DRUG

Pertuzumab

Participants will receive pertuzumab at a loading dose of 840 milligrams (mg) IV loading dose, then 420 mg IV q3w.

Intervention Type: DRUG

Trastuzumab

Participants will receive trastuzumab at a loading dose of 8 milligrams per kilogram (mg/kg) IV, then 6 mg/kg IV q3w.

Intervention Type: DRUG

Other Intervention Names

Perjeta; Herceptin

Eligibility Criteria

Inclusion Criteria

• Male and female participants with locally advanced, inflammatory, or early-stage, unilateral, and histologically confirmed invasive breast cancer. Participants with inflammatory breast cancer must be able to have a core needle biopsy
• Primary tumor greater than (>) 2 centimeters (cm) in diameter, or > 5 millimeters (mm) in diameter and node-positive
• HER2-positive breast cancer confirmed by a central laboratory
• Availability of tumor tissue specimen
• Baseline LVEF greater than or equal to (>/=) 55%
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (</=) 1
• At least 4 weeks since major unrelated surgery, with full recovery
• Women of childbearing potential and male participants with partners of childbearing potential must agree to use a "highly effective" non-hormonal form of contraception or two "effective" forms of non-hormonal contraception by the patient and/or partner. Contraception must continue for the duration of study treatment and for at least 7 months after the last dose of study treatment

Exclusion Criteria

• Metastatic disease (Stage IV) or bilateral breast cancer
• Participants who have had an incisional biopsy of the primary tumor or the primary tumor excised
• Prior breast or non-breast malignancy within 5 years prior to study entry, except for carcinoma in situ and basal cell and squamous cell carcinoma of the skin. Participants with malignancies occurring more than 5 years prior to study entry are permitted if curatively treated
• Any previous systemic therapy (including chemotherapy, immunotherapy, HER2 targeted agents, and antitumor vaccines) for cancer, or radiation therapy for cancer
• Participants with a past history of ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) are not allowed to enter the study if they have received any systemic therapy for its treatment or radiation therapy to the ipsilateral breast (they are allowed to enter the study if treated with surgery alone)
• High-risk participants who have received chemopreventive drugs in the past are not allowed to enter the study
• Inadequate bone marrow, renal, or liver function
• History or evidence of cardiovascular condition
• Dyspnea at rest or other diseases that require continuous oxygen therapy
• Severe, uncontrolled systemic disease
• Participants with poorly controlled diabetes or with evidence of clinically significant diabetic vascular complications
• Pregnancy or breast-feeding women
• Participants who received any investigational treatment within 4 weeks of study start
• Participants with known infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus
• Current chronic daily treatment with corticosteroids (dose >10 mg methylprednisolone or equivalent [excluding inhaled steroids])
• Known hypersensitivity to any of the study drugs or excipients

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• 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

University of South Alabama; Mitchell Cancer Institute

Mobile, Alabama, United States

Marin Specialty Care

Greenbrae, California, United States

California Pacific Medical Center

San Francisco, California, United States

MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center)

Washington D.C., District of Columbia, United States

Washington Cancer Institute at MedStar Washington Hospital Center.

Washington D.C., District of Columbia, United States

Cancer Specialists; North Florida ;Jacksonville (AC Skinner Pkwy)

Jacksonville, Florida, United States

Northwest Georgia Oncology Centers PC - Marietta

Marietta, Georgia, United States

Berkshire Medical Center

Pittsfield, Massachusetts, United States

Allina Health, Virginia Piper Cancer Institute

Minneapolis, Minnesota, United States

Saint Lukes Hospital Cancer Institute

Kansas City, Missouri, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Regional Cancer Care Associates LLC - Morristown

Morristown, New Jersey, United States

San Juan Oncology Associates

Farmington, New Mexico, United States

MSKCC @ Commack

Commack, New York, United States

MSKCC @ West Harrison

Harrison, New York, United States

Mount Sinai Beth Israel Comprehensive Cancer Center

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

MSKC @ Rockville

Rockville Centre, New York, United States

Mercy Clinic Oklahoma Communties, Inc

Oklahoma City, Oklahoma, United States

Harrington Cancer Center

Amarillo, Texas, United States

University of Utah; Huntsman Cancer Hospital

Salt Lake City, Utah, United States

Blue Ridge Cancer Care

Roanoke, Virginia, United States

PeaceHealth St. Joseph Cancer Center

Bellingham, Washington, United States

Northwest Medical Specialties

Tacoma, Washington, United States

Horizon Health Network

Moncton, New Brunswick, Canada

Royal Victoria Hospital

Barrie, Ontario, Canada

Cite de La Sante de Laval; Hemato-Oncologie

Laval, Quebec, Canada

St Mary's Hospital Center

Montreal, Quebec, Canada

Hopital Sacre-Coeur Research Centre

Montreal, Quebec, Canada

Allan Blair Cancer Centre

Regina, Saskatchewan, Canada

Herlev Hospital; Afdeling for Kræftbehandling

Herlev, , Denmark

Rigshospitalet; Onkologisk Klinik

København Ø, , Denmark

Vejle Sygehus; Onkologisk Afdeling

Vejle, , Denmark

Clinique Victor Hugo; Chimiotherapie

Le Mans, , France

Centre Oscar Lambret; Cancerologie Gynecologique

Lille, , France

Centre Leon Berard; Departement Oncologie Medicale

Lyon, , France

Clinique Clementville; Hopital De Jour

Montpellier, , France

Centre D'Oncologie de Gentilly; Oncology

Nancy, , France

Centre Antoine Lacassagne; Hopital De Jour A2

Nice, , France

Institut Curie; Oncologie Medicale

Paris, , France

Centre Eugene Marquis; Unite Huguenin

Rennes, , France

Institut Gustave Roussy; Departement Oncologie Medicale

Villejuif, , France

Universitätsklinikum "Carl Gustav Carus"; Frauenheilkunde und Geburtshilfe

Dresden, , Germany

Dres.Andreas Ammon und Dirk Meyer

Göttingen, , Germany

Dres. Andreas Köhler und Roswitha Fuchs

Langen, , Germany

Klinikum rechts der Isar der TU München; Klinik und Poliklinik für Frauenheilkunde

München, , Germany

Ruppiner Kliniken, Klinik fuer Gynaekologie und Geburtshilfe

Neuruppin, , Germany

Asl Le-Ospedale "Vito Fazzi";U.O. Oncologia

Lecce, Apulia, Italy

Policlinico Umberto i di Roma; dip. Scienze Radiologiche, Oncologiche, Anatomopatologiche

Rome, Lazio, Italy

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

Turin, Piedmont, Italy

Casa Di Cura Di Alta Specialita La Maddalena; Dept. Oncologico Di Iii Livello

Palermo, Sicily, Italy

Ospedale Santa Maria Annunziata; Oncologia

Bagno a Ripoli, Tuscany, Italy

Ospedale Della Misericordia; U.O. Di Medicina Ia - Oncologia Medica

Grosseto, Tuscany, Italy

Iem-Fucam

D.F., , Mexico

Centro de Diagnóstico y Tratamiento Integral de Mama, Hospital San José Tec de Monterrey

Monterrey, , Mexico

Haukeland Universitetssjukehus; Klinisk forskningspost

Bergen, , Norway

Oslo universitetssykehus HF, Ullevål, Kreftsenteret

Oslo, , Norway

Bialostockie Centrum Onkologii; Oddzial Onkologii Klinicznej

Bialystok, , Poland

Szpital Uniwersytecki w Krakowie, Oddział Kliniczny Kliniki Onkologii

Krakow, , Poland

Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina, Klinika Onkologii

Otwock, , Poland

Wielkopolskie Centrum Onkologii; im. Marii Skłodowskiej-Curie

Poznan, , Poland

Centro Clinico Champalimaud; Oncologia Medica

Lisbon, , Portugal

Hospital de Santa Maria; Servico de Oncologia Medica

Lisbon, , Portugal

Hospital Beatriz Angelo; Departamento de Oncologia

Loures, , Portugal

IPO do Porto; Servico de Oncologia Medica

Porto, , Portugal

Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia

Badalona, Barcelona, Spain

Hospital Universitario Reina Sofia; Servicio de Oncologia

Córdoba, Cordoba, Spain

Centro Oncológico Gallego José Antonio Quiroga y Piñeiro, Servicio de Oncologia

A Coruña, , Spain

Hospital Universitario de la Princesa; Servicio de Oncologia

Madrid, , Spain

Hospital Ramon y Cajal; Servicio de Oncologia

Madrid, , Spain

Hospital Universitario Virgen Macarena; Servicio de Oncologia

Seville, , Spain

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

Toledo, , Spain

Royal United Hospital; Oncology Department

Bath, , United Kingdom

Royal Bournemouth Hospital; Oncology

Bournemouth, , United Kingdom

Guys & St Thomas Hospital; Department of Oncology

London, , United Kingdom

Royal Marsden Hospital - Fulham; Oncology Department

London, , United Kingdom

Freeman Hospital; Northern Centre For Cancer Care

New Castle Upon Tyne, , United Kingdom

Churchill Hospital; Oxford Cancer and Haematology Centre

Oxford, , United Kingdom

Peterborough City Hospital, Edith Cavell Campus; Oncology Department

Peterborough, , United Kingdom

Royal Marsden Hospital; Dept of Medical Oncology

Sutton, , United Kingdom

Countries

United States; Canada; Denmark; France; Germany; Italy; Mexico; Norway; Poland; Portugal; Spain; United Kingdom

References

Swain SM, Ewer MS, Viale G, Delaloge S, Ferrero JM, Verrill M, Colomer R, Vieira C, Werner TL, Douthwaite H, Bradley D, Waldron-Lynch M, Kiermaier A, Eng-Wong J, Dang C; BERENICE Study Group. Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer (BERENICE): a phase II, open-label, multicenter, multinational cardiac safety study. Ann Oncol. 2018 Mar 1;29(3):646-653. doi: 10.1093/annonc/mdx773.

Reference Type: DERIVED

PMID: 29253081 (View on PubMed)

Other Identifiers

2014-000156-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

WO29217

Identifier Type: -

Identifier Source: org_study_id