Clinical trial NCT02132949: 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
Official title: A Multicenter, Multinational, Phase II Study to Evaluate Perjeta in Combination With Herceptin and Standard Neoadjuvant Anthracycline-Based Chemotherapy in Patients With HER2-Positive, Locally Advanced, Inflammatory, or Early-Stage Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2014-05-07
Enrollment: 401
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Percentage of Participants With at Least One Event of New York Heart Association (NYHA) Class III or IV Heart Failure During the Neoadjuvant Treatment Period
timeFrame: From day of first dose of pertuzumab or trastuzumab until the end of the neoadjuvant treatment period (as defined in the description; up to 25 weeks)
measure: Percentage of Participants With at Least One Left Ventricular Ejection Fraction (LVEF) Significant Decline, Defined as a Drop in LVEF of at Least 10 Percentage Points From Baseline and to Below 50%, During the Neoadjuvant Treatment Period
timeFrame: From day of first dose of pertuzumab or trastuzumab until the end of the neoadjuvant treatment period (as defined in the description; up to 25 weeks)
Secondary outcomes:
measure: Percentage of Participants With at Least One Event of New York Heart Association (NYHA) Class III or IV Heart Failure During the Adjuvant Treatment Period
timeFrame: From the first dose of any study drug after surgery through 42 days after the last dose of any study drug (during the adjuvant treatment period; up to approximately 39 weeks)
measure: Percentage of Participants With at Least One Left Ventricular Ejection Fraction (LVEF) Significant Decline, Defined as a Drop in LVEF of at Least 10 Percentage Points From Baseline and to Below 50%, During the Adjuvant Treatment Period
timeFrame: From the first dose of any study drug after surgery through 42 days after the last dose of any study drug (during the adjuvant treatment period; up to approximately 39 weeks)
measure: Percentage of Participants With at Least One Event of New York Heart Association (NYHA) Class III or IV Heart Failure During the Treatment-Free Follow-Up Period
timeFrame: From 42 days after the last dose of study treatment until the end of treatment-free follow-up (up to 5 years)
measure: Percentage of Participants With at Least One Left Ventricular Ejection Fraction (LVEF) Significant Decline, Defined as a Drop in LVEF of at Least 10 Percentage Points From Baseline and to Below 50%, During the Treatment-Free Follow-Up Period
timeFrame: From 42 days after the last dose of study treatment until the end of treatment-free follow-up (up to 5 years)
measure: Overview of the Number of Participants With at Least One Adverse Event During the Neoadjuvant Period
timeFrame: From first dose of any study drug prior to surgery through the day before the first dose of study drug after surgery (up to 25 weeks)
measure: Overview of the Number of Participants With at Least One Adverse Event During the Adjuvant Period
timeFrame: From the first dose of any study drug after surgery through 42 days after the last dose of any study drug (during the adjuvant treatment period; up to approximately 39 weeks)
measure: Overview of the Number of Participants With at Least One Adverse Event During the Treatment-Free Follow-Up Period
timeFrame: From 42 days after the last dose of study treatment until the end of treatment-free follow-up (TFFU; up to 5 years)
measure: Percentage of Participants Positive for Anti-Therapeutic Antibodies (ATAs) to Pertuzumab at Baseline and Anytime Post-Baseline
timeFrame: Screening (baseline) then prior to pertuzumab infusion (Hour 0) in Cycles 5, 14, 18 thereafter anytime between Cycle 8 Day 21 and surgery, up to treatment completion visit (cycle length=2-3 weeks; up to approximately 1 year, 3 months)
measure: Percentage of Participants With Total Pathologic Complete Response (tpCR), Evaluated After Surgery
timeFrame: After completion of neoadjuvant treatment and surgery (up to 25 weeks)
measure: Percentage of Participants With Clinical Response as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 During the Neoadjuvant Treatment Period
timeFrame: From Baseline until disease progression or death due to any cause up to 24 weeks (during the neoadjuvant treatment period; assessed on Day 1 of Cycles 1-8 [cycle length=2-3 weeks])
measure: Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Event-Free Survival (EFS) at 1 to 5 Years, Determined by the Investigator According to RECIST v1.1
timeFrame: At 1, 2, 3, 4, and 5 years
measure: Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Invasive Disease-Free Survival (iDFS) at 1 to 4 Years, Determined by the Investigator According to RECIST v1.1
timeFrame: At 1, 2, 3, and 4 years
measure: Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Overall Survival (OS) at 1 to 5 Years
timeFrame: At 1, 2, 3, 4, and 5 years
Other outcomes:
Locations:
city: Mobile
country: United States
facility: University of South Alabama; Mitchell Cancer Institute
state: Alabama
city: Greenbrae
country: United States
facility: Marin Specialty Care
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Washington
country: United States
facility: MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center)
state: District of Columbia
city: Washington
country: United States
facility: Washington Cancer Institute at MedStar Washington Hospital Center.
state: District of Columbia
city: Jacksonville
country: United States
facility: Cancer Specialists; North Florida ;Jacksonville (AC Skinner Pkwy)
state: Florida
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers PC - Marietta
state: Georgia
city: Pittsfield
country: United States
facility: Berkshire Medical Center
state: Massachusetts
city: Minneapolis
country: United States
facility: Allina Health, Virginia Piper Cancer Institute
state: Minnesota
city: Kansas City
country: United States
facility: Saint Lukes Hospital Cancer Institute
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Morristown
country: United States
facility: Regional Cancer Care Associates LLC - Morristown
state: New Jersey
city: Farmington
country: United States
facility: San Juan Oncology Associates
state: New Mexico
city: Commack
country: United States
facility: MSKCC @ Commack
state: New York
city: Harrison
country: United States
facility: MSKCC @ West Harrison
state: New York
city: New York
country: United States
facility: Mount Sinai Beth Israel Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rockville Centre
country: United States
facility: MSKC @ Rockville
state: New York
city: Oklahoma City
country: United States
facility: Mercy Clinic Oklahoma Communties, Inc
state: Oklahoma
city: Amarillo
country: United States
facility: Harrington Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah; Huntsman Cancer Hospital
state: Utah
city: Roanoke
country: United States
facility: Blue Ridge Cancer Care
state: Virginia
city: Bellingham
country: United States
facility: PeaceHealth St. Joseph Cancer Center
state: Washington
city: Tacoma
country: United States
facility: Northwest Medical Specialties
state: Washington
city: Moncton
country: Canada
facility: Horizon Health Network
state: New Brunswick
city: Barrie
country: Canada
facility: Royal Victoria Hospital
state: Ontario
city: Laval
country: Canada
facility: Cite de La Sante de Laval; Hemato-Oncologie
state: Quebec
city: Montreal
country: Canada
facility: St Mary's Hospital Center
state: Quebec
city: Montreal
country: Canada
facility: Hopital Sacre-Coeur Research Centre
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
city: Herlev
country: Denmark
facility: Herlev Hospital; Afdeling for Kræftbehandling
city: København Ø
country: Denmark
facility: Rigshospitalet; Onkologisk Klinik
city: Vejle
country: Denmark
facility: Vejle Sygehus; Onkologisk Afdeling
city: Le Mans
country: France
facility: Clinique Victor Hugo; Chimiotherapie
city: Lille
country: France
facility: Centre Oscar Lambret; Cancerologie Gynecologique
city: Lyon
country: France
facility: Centre Leon Berard; Departement Oncologie Medicale
city: Montpellier
country: France
facility: Clinique Clementville; Hopital De Jour
city: Nancy
country: France
facility: Centre D'Oncologie de Gentilly; Oncology
city: Nice
country: France
facility: Centre Antoine Lacassagne; Hopital De Jour A2
city: Paris
country: France
facility: Institut Curie; Oncologie Medicale
city: Rennes
country: France
facility: Centre Eugene Marquis; Unite Huguenin
city: Villejuif
country: France
facility: Institut Gustave Roussy; Departement Oncologie Medicale
city: Dresden
country: Germany
facility: Universitätsklinikum "Carl Gustav Carus"; Frauenheilkunde und Geburtshilfe
city: Göttingen
country: Germany
facility: Dres.Andreas Ammon und Dirk Meyer
city: Langen
country: Germany
facility: Dres. Andreas Köhler und Roswitha Fuchs
city: München
country: Germany
facility: Klinikum rechts der Isar der TU München; Klinik und Poliklinik für Frauenheilkunde
city: Neuruppin
country: Germany
facility: Ruppiner Kliniken, Klinik fuer Gynaekologie und Geburtshilfe
city: Roma
country: Italy
facility: Policlinico Umberto i di Roma; dip. Scienze Radiologiche, Oncologiche, Anatomopatologiche
state: Lazio
city: Torino
country: Italy
facility: A.O. Città della Salute e della Scienza - Presidio Molinette; divisione oncologia medica
state: Piemonte
city: Lecce
country: Italy
facility: Asl Le-Ospedale "Vito Fazzi";U.O. Oncologia
state: Puglia
city: Palermo
country: Italy
facility: Casa Di Cura Di Alta Specialita La Maddalena; Dept. Oncologico Di Iii Livello
state: Sicilia
city: Bagno a Ripoli
country: Italy
facility: Ospedale Santa Maria Annunziata; Oncologia
state: Toscana
city: Grosseto
country: Italy
facility: Ospedale Della Misericordia; U.O. Di Medicina Ia - Oncologia Medica
state: Toscana
city: D.f.
country: Mexico
facility: Iem-Fucam
city: Monterrey
country: Mexico
facility: Centro de Diagnóstico y Tratamiento Integral de Mama, Hospital San José Tec de Monterrey
city: Bergen
country: Norway
facility: Haukeland Universitetssjukehus; Klinisk forskningspost
city: Oslo
country: Norway
facility: Oslo universitetssykehus HF, Ullevål, Kreftsenteret
city: Bialystok
country: Poland
facility: Bialostockie Centrum Onkologii; Oddzial Onkologii Klinicznej
city: Kraków
country: Poland
facility: Szpital Uniwersytecki w Krakowie, Oddział Kliniczny Kliniki Onkologii
city: Otwock
country: Poland
facility: Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina, Klinika Onkologii
city: Poznan
country: Poland
facility: Wielkopolskie Centrum Onkologii; im. Marii Skłodowskiej-Curie
city: Lisboa
country: Portugal
facility: Centro Clinico Champalimaud; Oncologia Medica
city: Lisboa
country: Portugal
facility: Hospital de Santa Maria; Servico de Oncologia Medica
city: Loures
country: Portugal
facility: Hospital Beatriz Angelo; Departamento de Oncologia
city: Porto
country: Portugal
facility: IPO do Porto; Servico de Oncologia Medica
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia
state: Barcelona
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia; Servicio de Oncologia
state: Cordoba
city: La Coruña
country: Spain
facility: Centro Oncológico Gallego José Antonio Quiroga y Piñeiro, Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario de la Princesa; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal; Servicio de Oncologia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena; Servicio de Oncologia
city: Toledo
country: Spain
facility: Complejo Hospitalario de Toledo- H. Virgen de la Salud; Servicio de Oncologia
city: Bath
country: United Kingdom
facility: Royal United Hospital; Oncology Department
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital; Oncology
city: London
country: United Kingdom
facility: Guys & St Thomas Hospital; Department of Oncology
city: London
country: United Kingdom
facility: Royal Marsden Hospital - Fulham; Oncology Department
city: New Castle Upon Tyne
country: United Kingdom
facility: Freeman Hospital; Northern Centre For Cancer Care
city: Oxford
country: United Kingdom
facility: Churchill Hospital; Oxford Cancer and Haematology Centre
city: Peterborough
country: United Kingdom
facility: Peterborough City Hospital, Edith Cavell Campus; Oncology Department
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital; Dept of Medical Oncology
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.