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

NCT02132949 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: WO292172014-000156-28
• Study Type: interventional
• Target: 401
• Locations: 12 countries
• Sites: 80

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

Outcome Measures

Primary Outcomes (2)

• 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

  Symptomatic left ventricular systolic dysfunction (otherwise referred to as heart failure) is a serious adverse event. The NYHA Functional Classification System for Heart Failure considers the patient's symptoms: Class III: Marked limitation of physical activity; Comfortable at rest, but less than ordinary activity causes fatigue, palpitation, or dyspnea. Class IV: Unable to carry on any physical activity without discomfort; Symptoms of heart failure at rest; If any physical activity is undertaken, discomfort increases. The 95% CIs were calculated with the Clopper-Pearson method. Results included events with onset from first dose of pertuzumab/trastuzumab prior to surgery through the day before the first dose of any study drug after surgery. If participant withdrew without entering adjuvant period, results included all events with onset from first dose of pertuzumab/trastuzumab through 42 days after last dose of any study drug or on the day of target surgery whichever was later.

  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)

• 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

  LVEF significant decline was defined as the decline in LVEF of \>/= 10%-points from baseline to an LVEF of \< 50%. A Confirmed LVEF Significant Decline was defined as at least two consecutive readings of significant declines in LVEF. A Single LVEF Significant Decline was defined as only one reading of a significant decline (no consecutive readings) in LVEF. The category of 'At Least one LVEF Significant Decline Event' was defined as the total of confirmed and single LVEF significant declines. The 95% confidence intervals (CIs) were calculated using the Clopper-Pearson method. Results include events with onset from the first dose of pertuzumab or trastuzumab prior to surgery through the day before the first dose of any study drug after surgery. If participant withdrew without entering adjuvant period, results included all events with onset from first dose of pertuzumab or trastuzumab through 42 days after last dose of any study drug or on the day of target surgery whichever is later.

  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 (13)

• 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

  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)

• 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

  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)

• 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

  From 42 days after the last dose of study treatment until the end of treatment-free follow-up (up to 5 years)

• 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

  From 42 days after the last dose of study treatment until the end of treatment-free follow-up (up to 5 years)

• Overview of the Number of Participants With at Least One Adverse Event During the Neoadjuvant Period

  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)

Study Arms (2)

Cohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab

EXPERIMENTAL

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.

Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Paclitaxel; Drug: Pertuzumab; Drug: Trastuzumab

Cohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab

EXPERIMENTAL

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.

Drug: 5-Fluorouracil; Drug: Cyclophosphamide; Drug: Docetaxel; Drug: Epirubicin; Drug: Pertuzumab; Drug: Trastuzumab

Interventions

5-Fluorouracil DRUG

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

Cohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab

Cyclophosphamide DRUG

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

Cohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab; Cohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab

Docetaxel 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.

Cohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab

Doxorubicin DRUG

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

Cohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab

Epirubicin DRUG

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

Cohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab

Paclitaxel DRUG

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

Cohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab

Pertuzumab DRUG

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

Also known as: Perjeta

Cohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab; Cohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab

Trastuzumab DRUG

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

Also known as: Herceptin

Cohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab; Cohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 \[excluding inhaled steroids\])

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (80)

University of South Alabama; Mitchell Cancer Institute

Mobile, Alabama, 36604, United States

Location

Marin Specialty Care

Greenbrae, California, 94904, United States

Location

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center)

Washington D.C., District of Columbia, 20007, United States

Location

Washington Cancer Institute at MedStar Washington Hospital Center.

Washington D.C., District of Columbia, 20010, United States

Location

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

Jacksonville, Florida, 32256, United States

Location

Northwest Georgia Oncology Centers PC - Marietta

Marietta, Georgia, 30060, United States

Location

Berkshire Medical Center

Pittsfield, Massachusetts, 01201, United States

Location

Allina Health, Virginia Piper Cancer Institute

Minneapolis, Minnesota, 55407, United States

Location

Saint Lukes Hospital Cancer Institute

Kansas City, Missouri, 64111, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Regional Cancer Care Associates LLC - Morristown

Morristown, New Jersey, 07962, United States

Location

San Juan Oncology Associates

Farmington, New Mexico, 87401, United States

Location

MSKCC @ Commack

Commack, New York, 11725, United States

Location

MSKCC @ West Harrison

Harrison, New York, 10604, United States

Location

Mount Sinai Beth Israel Comprehensive Cancer Center

New York, New York, 10011, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

MSKC @ Rockville

Rockville Centre, New York, 11570, United States

Location

Mercy Clinic Oklahoma Communties, Inc

Oklahoma City, Oklahoma, 73120, United States

Location

Harrington Cancer Center

Amarillo, Texas, 79106, United States

Location

University of Utah; Huntsman Cancer Hospital

Salt Lake City, Utah, 84112, United States

Location

Blue Ridge Cancer Care

Roanoke, Virginia, 24014, United States

Location

PeaceHealth St. Joseph Cancer Center

Bellingham, Washington, 98225, United States

Location

Northwest Medical Specialties

Tacoma, Washington, 98405, United States

Location

Horizon Health Network

Moncton, New Brunswick, E1C 6Z8, Canada

Location

Royal Victoria Hospital

Barrie, Ontario, L4M 6M2, Canada

Location

Cite de La Sante de Laval; Hemato-Oncologie

Laval, Quebec, H7M 3L9, Canada

Location

St Mary's Hospital Center

Montreal, Quebec, H3T1M5, Canada

Location

Hopital Sacre-Coeur Research Centre

Montreal, Quebec, H4J 1C5, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

Location

Herlev Hospital; Afdeling for Kræftbehandling

Herlev, 2730, Denmark

Location

Rigshospitalet; Onkologisk Klinik

København Ø, 2100, Denmark

Location

Vejle Sygehus; Onkologisk Afdeling

Vejle, 7100, Denmark

Location

Clinique Victor Hugo; Chimiotherapie

Le Mans, 72015, France

Location

Centre Oscar Lambret; Cancerologie Gynecologique

Lille, 59020, France

Location

Centre Leon Berard; Departement Oncologie Medicale

Lyon, 69373, France

Location

Clinique Clementville; Hopital De Jour

Montpellier, 34070, France

Location

Centre D'Oncologie de Gentilly; Oncology

Nancy, 54100, France

Location

Centre Antoine Lacassagne; Hopital De Jour A2

Nice, 06189, France

Location

Institut Curie; Oncologie Medicale

Paris, 75231, France

Location

Centre Eugene Marquis; Unite Huguenin

Rennes, 35042, France

Location

Institut Gustave Roussy; Departement Oncologie Medicale

Villejuif, 94805, France

Location

Universitätsklinikum "Carl Gustav Carus"; Frauenheilkunde und Geburtshilfe

Dresden, 01307, Germany

Location

Dres.Andreas Ammon und Dirk Meyer

Göttingen, 37073, Germany

Location

Dres. Andreas Köhler und Roswitha Fuchs

Langen, 63225, Germany

Location

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

München, 81675, Germany

Location

Ruppiner Kliniken, Klinik fuer Gynaekologie und Geburtshilfe

Neuruppin, 16816, Germany

Location

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

Lecce, Apulia, 73100, Italy

Location

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

Rome, Lazio, 00161, Italy

Location

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

Turin, Piedmont, 10126, Italy

Location

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

Palermo, Sicily, 90146, Italy

Location

Ospedale Santa Maria Annunziata; Oncologia

Bagno a Ripoli, Tuscany, 50012, Italy

Location

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

Grosseto, Tuscany, 58100, Italy

Location

Iem-Fucam

D.F., 04980, Mexico

Location

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

Monterrey, 64710, Mexico

Location

Haukeland Universitetssjukehus; Klinisk forskningspost

Bergen, 5021, Norway

Location

Oslo universitetssykehus HF, Ullevål, Kreftsenteret

Oslo, 0450, Norway

Location

Bialostockie Centrum Onkologii; Oddzial Onkologii Klinicznej

Bialystok, 15-027, Poland

Location

Szpital Uniwersytecki w Krakowie, Oddział Kliniczny Kliniki Onkologii

Krakow, 30-688, Poland

Location

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

Otwock, 05-400, Poland

Location

Wielkopolskie Centrum Onkologii; im. Marii Skłodowskiej-Curie

Poznan, 61-866, Poland

Location

Centro Clinico Champalimaud; Oncologia Medica

Lisbon, 1400-038, Portugal

Location

Hospital de Santa Maria; Servico de Oncologia Medica

Lisbon, 1649-035, Portugal

Location

Hospital Beatriz Angelo; Departamento de Oncologia

Loures, 2674-514, Portugal

Location

IPO do Porto; Servico de Oncologia Medica

Porto, 4200-072, Portugal

Location

Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia

Badalona, Barcelona, 08916, Spain

Location

Hospital Universitario Reina Sofia; Servicio de Oncologia

Córdoba, Cordoba, 14004, Spain

Location

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

A Coruña, 15009, Spain

Location

Hospital Universitario de la Princesa; Servicio de Oncologia

Madrid, 28006, Spain

Location

Hospital Ramon y Cajal; Servicio de Oncologia

Madrid, 28034, Spain

Location

Hospital Universitario Virgen Macarena; Servicio de Oncologia

Seville, 41009, Spain

Location

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

Toledo, 45004, Spain

Location

Royal United Hospital; Oncology Department

Bath, BA1 3NG, United Kingdom

Location

Royal Bournemouth Hospital; Oncology

Bournemouth, BH7 7DW, United Kingdom

Location

Guys & St Thomas Hospital; Department of Oncology

London, SE1 9RT, United Kingdom

Location

Royal Marsden Hospital - Fulham; Oncology Department

London, SW3 6JJ, United Kingdom

Location

Freeman Hospital; Northern Centre For Cancer Care

New Castle Upon Tyne, NE7 7DN, United Kingdom

Location

Churchill Hospital; Oxford Cancer and Haematology Centre

Oxford, OX3 7LJ, United Kingdom

Location

Peterborough City Hospital, Edith Cavell Campus; Oncology Department

Peterborough, PE3 9GZ, United Kingdom

Location

Royal Marsden Hospital; Dept of Medical Oncology

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 29253081 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Fluorouracil; Cyclophosphamide; Docetaxel; Doxorubicin; Epirubicin; Paclitaxel; pertuzumab; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Diterpenes; Terpenes; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2014
• First Posted: May 7, 2014
• Study Start: July 14, 2014
• Primary Completion: March 3, 2016
• Study Completion: August 25, 2020
• Last Updated: September 17, 2021
• Results First Posted: April 13, 2017

Record last verified: 2021-08

Locations

NO (2); DK (3); ES (7); DE (5); PL (4); ME (2); US (24); PT (4); GB (8); FR (9); IT (6); CA (6)