A Study of Pertuzumab in Combination With Trastuzumab Plus an Aromatase Inhibitor in Participants With Metastatic Human Epidermal Growth Factor Receptor 2 (HER2)-Positive and Hormone Receptor-Positive Advanced Breast Cancer

NCT01491737 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: MO277752011-002132-10
• Study Type: interventional
• Target: 258
• Locations: 8 countries
• Sites: 82

Brief Summary

This randomized, open-label, two-arm, multi-center, Phase II study will evaluate the efficacy and safety of pertuzumab in combination with trastuzumab plus an aromatase inhibitor (AI) in first-line participants with HER2-positive and hormone receptor-positive advanced breast cancer. Participants will be randomized to one of two treatment arms; Arm A (pertuzumab in combination with trastuzumab plus an AI) or Arm B (trastuzumab plus an AI). Participants may also receive induction chemotherapy (a taxane, either docetaxel or paclitaxel) at the investigator's discretion in combination with the assigned treatment arm. The anticipated time on study treatment is until disease progression, unacceptable toxicity, withdrawal of consent, or death whichever occurs first.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  Progression-free survival (PFS) was defined as the time from randomization until the first radiographically documented progression of disease or death from any cause, whichever occurred first (either during study treatment or during follow-up). Progression of disease was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 and is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum of target lesion diameters must also demonstrate an absolute increase of at least 5 mm (Note: the appearance of one or more new lesions is also considered progression). Participants with no PFS events were censored at the time of the last evaluable tumor assessment. The primary analysis of PFS was planned to be performed when a total of 165 PFS events had occurred, and the final analysis after at least 60 months follow-up.

  Median [full range] of follow-up time on study for: Primary Analysis: 31.7 [0.0-44.3] months vs. 30.4 [0.0-45.8] months in Arm A vs. Arm B; Final Analysis: 73.20 [0.03-88.34] months vs. 71.06 [0.03-88.97] months in Arm A vs. Arm B

Secondary Outcomes (9)

• Overall Survival (OS)

  Median [full range] of follow-up time on study for: Primary Analysis: 31.7 [0.0-44.3] months vs. 30.4 [0.0-45.8] months in Arm A vs. Arm B; Final Analysis: 73.20 [0.03-88.34] months vs. 71.06 [0.03-88.97] months in Arm A vs. Arm B

• Overall Response Rate (ORR)

  Median [full range] of follow-up time on study for Primary Analysis: 31.7 [0.0-44.3] months vs. 30.4 [0.0-45.8] months in Arm A vs. Arm B

• Clinical Benefit Rate (CBR)

  Median [full range] of follow-up time on study for Primary Analysis: 31.7 [0.0-44.3] months vs. 30.4 [0.0-45.8] months in Arm A vs. Arm B

• Duration of Response (DOR)

  Median [full range] of follow-up time on study for: Primary Analysis: 31.7 [0.0-44.3] months vs. 30.4 [0.0-45.8] months in Arm A vs. Arm B; Final Analysis: 73.20 [0.03-88.34] months vs. 71.06 [0.03-88.97] months in Arm A vs. Arm B

• Time to Response (TTR)

  Median [full range] of follow-up time on study for Primary Analysis: 31.7 [0.0-44.3] months vs. 30.4 [0.0-45.8] months in Arm A vs. Arm B

Study Arms (2)

Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy

EXPERIMENTAL

Participants will receive pertuzumab in combination with trastuzumab plus aromatase inhibitor (AI) until pre-defined study end, disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first. Participants may also receive induction chemotherapy (docetaxel every 3 weeks or paclitaxel weekly) up to the first 18-24 weeks of the treatment period at the investigator's discretion.

Drug: Pertuzumab; Drug: Trastuzumab; Drug: Aromatase Inhibitor; Drug: Induction Chemotherapy

Arm B: Trastuzumab + AI +/- Chemotherapy

ACTIVE COMPARATOR

Participants will receive trastuzumab plus aromatase inhibitor (AI) until predefined study end, disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first. Participants may also receive induction chemotherapy (docetaxel every 3 weeks or paclitaxel weekly) up to the first 18-24 weeks of the treatment period at the investigator's discretion.

Drug: Trastuzumab; Drug: Aromatase Inhibitor; Drug: Induction Chemotherapy

Interventions

Pertuzumab DRUG

Participants will receive a loading dose of 840 milligrams (mg) as an intravenous infusion on Day 1 of first treatment cycle, followed by 420 mg on Day 1 or Day 2 of each subsequent 3-week cycle until disease progression or unacceptable toxicity.

Also known as: Perjeta®, rhuMAb 2C4

Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy

Trastuzumab DRUG

Participants will receive a loading dose of 8 milligrams per kilogram (mg/kg) as an intravenous infusion on Day 1 or 2 of first treatment cycle, followed by 6 mg/kg on Day 1 or Day 2 of each subsequent treatment 3-week cycles until disease progression or unacceptable toxicity.

Also known as: Herceptin®, rhuMAb HER2

Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy; Arm B: Trastuzumab + AI +/- Chemotherapy

Aromatase Inhibitor DRUG

Participants will receive 1 mg anastrozole or 2.5 mg letrozole orally once daily.

Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy; Arm B: Trastuzumab + AI +/- Chemotherapy

Induction Chemotherapy DRUG

Participants receiving induction chemotherapy up to the first 18-24 weeks of the treatment period will receive a taxane (docetaxel every 3 weeks or paclitaxel weekly), administered in line with the respective pertuzumab and/or trastuzumab infusions at the investigator's discretion.

Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy; Arm B: Trastuzumab + AI +/- Chemotherapy

Eligibility Criteria

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

You may qualify if:

• Participants with HER2-positive and hormone receptor-positive advanced metastatic or locally advanced breast cancer
• Post-menopausal status over 1 year
• HER2-positive as assessed by local laboratory on primary or metastatic tumor
• Hormone-receptor positive defined as estrogen receptor-positive and/or progesterone receptor-positive
• At least one measurable lesion and/or non-measurable disease evaluable according to Response Evaluation Criteria In Solid Tumors Version 1.1

You may not qualify if:

• Previous systemic non-hormonal anticancer therapy in the metastatic or locally advanced breast cancer setting
• Previous treatment with anti-HER2 agents for breast cancer, except trastuzumab and/or lapatinib in the neoadjuvant or adjuvant setting
• Disease progression while receiving adjuvant trastuzumab and/or lapatinib treatment
• History of persistent Grade 2 or higher hematological toxicity according to National Cancer Institute-Common Toxicity Criteria Version 4.0
• Disease-free interval from completion of adjuvant/neo-adjuvant systemic non-hormonal treatment to recurrence of within 6 months
• Other malignancies within the last 5 years, except for carcinoma in situ of the cervix or basal cell carcinoma
• Clinical or radiographic evidence of central nervous system metastases or significant cardiovascular disease

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (82)

University of Alabama at Birmingham

Birmingham, Alabama, 35249, United States

Location

Ironwood Cancer TX & Rsch Ctrs

Chandler, Arizona, 85224, United States

Location

Genesis Cancer Center

Hot Springs, Arkansas, 71913, United States

Location

Comprehensive Blood & CA Ctr; Research

Bakersfield, California, 93309, United States

Location

Rocky Mountain Cancer Center - Denver

Denver, Colorado, 80220, United States

Location

Norwalk Hospital

Norwalk, Connecticut, 06856, United States

Location

Advanced Medical Specialties

Miami, Florida, 33176, United States

Location

Georgia Cancer Specialists - Northside

Atlanta, Georgia, 30341, United States

Location

Northwest Georgia Oncology Centers, a Service of WellStar Cobb Hospital

Marietta, Georgia, 30060, United States

Location

Cancer Center of Kansas

Wichita, Kansas, 67214-3728, United States

Location

Crescent City Rsrch Cnsrtm, LLC

Marrero, Louisiana, 70072, United States

Location

Weinberg CA Inst Franklin Sq

Baltimore, Maryland, 21237, United States

Location

Center For Cancer and Blood Disorders

Bethesda, Maryland, 20817, United States

Location

Washington University School of Medicine; Internal Medicine - Renal

St Louis, Missouri, 63110, United States

Location

Hematology Oncology Associates; Carol G. Simon Ctr

Morristown, New Jersey, 07960, United States

Location

Cooper Hospital; Hematology & Oncology

Voorhees Township, New Jersey, 08043, United States

Location

NS-Long Island Jewish Hlth Sys

Lake Success, New York, 11042, United States

Location

ProHEALTH Care Associates LLP

Lake Success, New York, 11042, United States

Location

UPMC Cancer Centers

Pittsburgh, Pennsylvania, 15232, United States

Location

Baylor College of Medicine; Lester & Sue Smith Breast Ctr

Houston, Texas, 77030, United States

Location

Scott and White Hospital; Cancer Center

Temple, Texas, 76508, United States

Location

Instituto do Cancer do Estado de Sao Paulo - ICESP

São Paulo, São Paulo, 01246-000, Brazil

Location

Hospital Perola Byington

São Paulo, São Paulo, 01317-904, Brazil

Location

Inst. Brasileiro de Controle Ao Cancer; Oncologia Clinica / Quimioterapia

São Paulo, São Paulo, 03102-002, Brazil

Location

Hospital Sao Jose

São Paulo, São Paulo, CEP 01321-001, Brazil

Location

HOPITAL JEAN MINJOZ; Oncologie

Besançon, 25030, France

Location

Clinique Tivoli; Sce Radiotherapie

Bordeaux, 33000, France

Location

Hopital Morvan; Oncologie - Radiotherapie

Brest, 29609, France

Location

Centre Jean Perrin; Oncologie

Clermont-Ferrand, 63011, France

Location

Clinique De La Sauvegarde; Chimiotherapie

Lyon, 69337, France

Location

Centre Catherine de Sienne; Chimiotherapie

Nantes, 44202, France

Location

Centre Antoine Lacassagne; Hopital De Jour A2

Nice, 06189, France

Location

CH De Senlis; Medecine 2

Senlis, 60309, France

Location

Clinique Pasteur; Oncologie Medicale

Toulouse, 31076, France

Location

Centre Alexis Vautrin; Oncologie Medicale

Vandœuvre-lès-Nancy, 54519, France

Location

Bangalore Institute of Oncology

Bangalore, Karnataka, 560027, India

Location

Jaslok Hospital & Research Centre; Medical Oncology

Mumbai, Maharashtra, 400026, India

Location

Indraprastha Apollo Hospitals

New Delhi, National Capital Territory of Delhi, 110076, India

Location

Apollo Speciality Hospital

Chennai, 600035, India

Location

Ruby Hall Clinic

Pune, 411 001, India

Location

Irccs Ist. Tumori Giovanni Paolo Ii; Dipartimento Oncologia Medica

Bari, Apulia, 70124, Italy

Location

Ospedale Antonio Perrino; Oncologia Medica

Brindisi, Apulia, 72100, Italy

Location

Ospedale Vito Fazzi; Div. Oncoematologia

Lecce, Apulia, 73100, Italy

Location

Istituto Nazionale Tumori Fondazione G. Pascale

Napoli, Campania, 80131, Italy

Location

Università degli Studi Federico II; Clinica di Oncologia Medica

Napoli, Campania, 80131, Italy

Location

Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica

Bologna, Emilia-Romagna, 40138, Italy

Location

Ospedale Regionale Di Parma; Divisione Di Oncologia Medica

Parma, Emilia-Romagna, 43100, Italy

Location

A.O. Santa Maria Degli Angeli; U.O Di Oncologia Medica

Pordenone, Friuli Venezia Giulia, 33170, Italy

Location

Ospedale S.S. Trinità Nuovo; Divisione Oncologia

Sora, Lazio, 03039, Italy

Location

Casa di Cura MultiMedica Ospedale di Castellanza; UO Senologia Medica

Castellanza, Lombardy, 21053, Italy

Location

Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 1

Milan, Lombardy, 20133, Italy

Location

IRCCS Fondazione Maugeri; Oncologia Medica I

Pavia, Lombardy, 27100, Italy

Location

Az Ospedaliera Nuovo Garibaldi Quartiere Nesima; Oncologia Medica

Catania, Sicily, 95122, Italy

Location

A.O. Careggi; Radioterapia

Florence, Tuscany, 50139, Italy

Location

Ospedale Misericordia E Dolce; Oncologia Medica

Prato, Tuscany, 59100, Italy

Location

Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia

Badalona, Barcelona, 08916, Spain

Location

Hospital Provincial de Castellon; Servicio de Oncologia

Castellon, Castellon, 12002, Spain

Location

Hospital Universitario Reina Sofia; Servicio de Oncologia

Córdoba, Cordoba, 14004, Spain

Location

IInstituto Oncologico de San Sebastian, Oncologikoa; Servicio de Oncologia

Donostia / San Sebastian, Guipuzcoa, 20014, Spain

Location

Hospital de Donostia; Servicio de Oncologia Medica

Donostia / San Sebastian, Guipuzcoa, 20080, Spain

Location

Complejo Hospitalario Universitario A Coruña (CHUAC, Materno Infantil), Oncología

A Coruña, 15006, Spain

Location

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

A Coruña, 15009, Spain

Location

Hospital del Mar; Servicio de Oncologia

Barcelona, 08003, Spain

Location

Hospital de San Pedro de Alcantara

Cáceres, 10003, Spain

Location

Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Oncologia

Lleida, 25198, Spain

Location

Hospital Ramon y Cajal; Servicio de Oncologia

Madrid, 28034, Spain

Location

Hospital Universitario Clínico San Carlos; Servicio de Oncologia

Madrid, 28040, Spain

Location

Hospital Universitario Virgen de Arrixaca; Servicio de Oncologia

Murcia, 30120, Spain

Location

Hospital Universitario Virgen Macarena; Servicio de Oncologia

Seville, 41009, Spain

Location

Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

Valencia, 46010, Spain

Location

Hospital Universitario Miguel Servet; Servicio Oncologia

Zaragoza, 50009, Spain

Location

Hacettepe Uni Medical Faculty Hospital; Oncology Dept

Ankara, 06100, Turkey (Türkiye)

Location

Ankara City Hospital

Ankara, 06490, Turkey (Türkiye)

Location

Ege Uni Medical Faculty Hospital; Oncology Dept

Izmir, 35100, Turkey (Türkiye)

Location

Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department

Malatya, 44280, Turkey (Türkiye)

Location

Brighton and Sussex Univ Hosp

Brighton, BN2 5BE, United Kingdom

Location

University Hospital coventry; Oncology Department

Coventry, CV2 2DX, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

Queen Elizabeth Hospital

London, SE18 4QH, United Kingdom

Location

Queen Alexandra Hospital, Portsmouth

Portsmouth, PO6 3LY, United Kingdom

Location

Scarborough General Hospital

Scarborough, YO12 6QL, United Kingdom

Location

Weston Park Hospital; Cancer Clinical Trials Centre

Sheffield, S10 2SJ, United Kingdom

Location

Related Publications (1)

• Rimawi M, Ferrero JM, de la Haba-Rodriguez J, Poole C, De Placido S, Osborne CK, Hegg R, Easton V, Wohlfarth C, Arpino G; PERTAIN Study Group. First-Line Trastuzumab Plus an Aromatase Inhibitor, With or Without Pertuzumab, in Human Epidermal Growth Factor Receptor 2-Positive and Hormone Receptor-Positive Metastatic or Locally Advanced Breast Cancer (PERTAIN): A Randomized, Open-Label Phase II Trial. J Clin Oncol. 2018 Oct 1;36(28):2826-2835. doi: 10.1200/JCO.2017.76.7863. Epub 2018 Aug 14.

  PMID: 30106636 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pertuzumab; Trastuzumab; Aromatase Inhibitors; Induction Chemotherapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Drug Therapy; Therapeutics; Remission Induction

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: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2011
• First Posted: December 14, 2011
• Study Start: February 17, 2012
• Primary Completion: March 17, 2016
• Study Completion: November 14, 2019
• Last Updated: October 28, 2020
• Results First Posted: June 7, 2017

Record last verified: 2020-10

Locations

ES (16); BR (4); FR (10); TU (4); US (21); GB (7); IN (5); IT (15)