Clinical trial NCT01491737: 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
Official title: A Randomized, Two-Arm, Open-Label, Multicenter Phase II Trial Assessing the Efficacy and Safety of Pertuzumab Given in Combination With Trastuzumab Plus an Aromatase Inhibitor in First Line Patients With HER2-Positive and Hormone Receptor-Positive Advanced (Metastatic or Locally Advanced) Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2011-12-14
Enrollment: 258
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: 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:
measure: Overall Survival (OS)
timeFrame: 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
measure: Overall Response Rate (ORR)
timeFrame: 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
measure: Clinical Benefit Rate (CBR)
timeFrame: 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
measure: Duration of Response (DOR)
timeFrame: 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
measure: Time to Response (TTR)
timeFrame: 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
measure: Change From Baseline in Health-Related Quality of Life as Determined by European Quality of Life 5-Dimension (EQ-5D) Visual Analog Scale (VAS) Scores
timeFrame: Baseline and every 3 cycles until treatment discontinuation (up to Cycle 120; 1 cycle is 21 days)
measure: Overview of the Number of Participants With Adverse Events, Severity Determined According to NCI-CTCAE Version 4.03
timeFrame: From Baseline until the end of post-treatment follow-up (up to 89 months)
measure: Number of Participants Who Died Over the Course of the Study by Reported Cause of Death and Time of Death Relative to First or Last Dose of Study Treatment
timeFrame: From Baseline until the end of post-treatment follow-up (up to 89 months)
measure: Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Values Over the Course of the Study
timeFrame: Baseline and every 3 cycles until treatment discontinuation (up to Cycle 120; 1 cycle is 21 days)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Chandler
country: United States
facility: Ironwood Cancer TX & Rsch Ctrs
state: Arizona
city: Hot Springs
country: United States
facility: Genesis Cancer Center
state: Arkansas
city: Bakersfield
country: United States
facility: Comprehensive Blood & CA Ctr; Research
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Center - Denver
state: Colorado
city: Norwalk
country: United States
facility: Norwalk Hospital
state: Connecticut
city: Miami
country: United States
facility: Advanced Medical Specialties
state: Florida
city: Atlanta
country: United States
facility: Georgia Cancer Specialists - Northside
state: Georgia
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers, a Service of WellStar Cobb Hospital
state: Georgia
city: Wichita
country: United States
facility: Cancer Center of Kansas
state: Kansas
city: Marrero
country: United States
facility: Crescent City Rsrch Cnsrtm, LLC
state: Louisiana
city: Baltimore
country: United States
facility: Weinberg CA Inst Franklin Sq
state: Maryland
city: Bethesda
country: United States
facility: Center For Cancer and Blood Disorders
state: Maryland
city: Saint Louis
country: United States
facility: Washington University School of Medicine; Internal Medicine - Renal
state: Missouri
city: Morristown
country: United States
facility: Hematology Oncology Associates; Carol G. Simon Ctr
state: New Jersey
city: Voorhees
country: United States
facility: Cooper Hospital; Hematology & Oncology
state: New Jersey
city: Lake Success
country: United States
facility: NS-Long Island Jewish Hlth Sys
state: New York
city: Lake Success
country: United States
facility: ProHEALTH Care Associates LLP
state: New York
city: Pittsburgh
country: United States
facility: UPMC Cancer Centers
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College of Medicine; Lester & Sue Smith Breast Ctr
state: Texas
city: Temple
country: United States
facility: Scott and White Hospital; Cancer Center
state: Texas
city: Sao Paulo
country: Brazil
facility: Instituto do Cancer do Estado de Sao Paulo - ICESP
state: SP
city: Sao Paulo
country: Brazil
facility: Hospital Perola Byington
state: SP
city: Sao Paulo
country: Brazil
facility: Inst. Brasileiro de Controle Ao Cancer; Oncologia Clinica / Quimioterapia
state: SP
city: São Paulo
country: Brazil
facility: Hospital Sao Jose
state: SP
city: Besancon
country: France
facility: HOPITAL JEAN MINJOZ; Oncologie
city: Bordeaux
country: France
facility: Clinique Tivoli; Sce Radiotherapie
city: Brest
country: France
facility: Hopital Morvan; Oncologie - Radiotherapie
city: Clermont Ferrand
country: France
facility: Centre Jean Perrin; Oncologie
city: Lyon
country: France
facility: Clinique De La Sauvegarde; Chimiotherapie
city: Nantes
country: France
facility: Centre Catherine de Sienne; Chimiotherapie
city: Nice
country: France
facility: Centre Antoine Lacassagne; Hopital De Jour A2
city: Senlis
country: France
facility: CH De Senlis; Medecine 2
city: Toulouse
country: France
facility: Clinique Pasteur; Oncologie Medicale
city: Vandoeuvre-les-nancy
country: France
facility: Centre Alexis Vautrin; Oncologie Medicale
city: New Delhi
country: India
facility: Indraprastha Apollo Hospitals
state: Delhi
city: Bangalore
country: India
facility: Bangalore Institute of Oncology
state: Karnataka
city: Mumbai
country: India
facility: Jaslok Hospital & Research Centre; Medical Oncology
state: Maharashtra
city: Chennai
country: India
facility: Apollo Speciality Hospital
city: Pune
country: India
facility: Ruby Hall Clinic
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione G. Pascale
state: Campania
city: Napoli
country: Italy
facility: Università degli Studi Federico II; Clinica di Oncologia Medica
state: Campania
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica
state: Emilia-Romagna
city: Parma
country: Italy
facility: Ospedale Regionale Di Parma; Divisione Di Oncologia Medica
state: Emilia-Romagna
city: Pordenone
country: Italy
facility: A.O. Santa Maria Degli Angeli; U.O Di Oncologia Medica
state: Friuli-Venezia Giulia
city: Sora
country: Italy
facility: Ospedale S.S. Trinità Nuovo; Divisione Oncologia
state: Lazio
city: Castellanza
country: Italy
facility: Casa di Cura MultiMedica Ospedale di Castellanza; UO Senologia Medica
state: Lombardia
city: Milano
country: Italy
facility: Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 1
state: Lombardia
city: Pavia
country: Italy
facility: IRCCS Fondazione Maugeri; Oncologia Medica I
state: Lombardia
city: Bari
country: Italy
facility: Irccs Ist. Tumori Giovanni Paolo Ii; Dipartimento Oncologia Medica
state: Puglia
city: Brindisi
country: Italy
facility: Ospedale Antonio Perrino; Oncologia Medica
state: Puglia
city: Lecce
country: Italy
facility: Ospedale Vito Fazzi; Div. Oncoematologia
state: Puglia
city: Catania
country: Italy
facility: Az Ospedaliera Nuovo Garibaldi Quartiere Nesima; Oncologia Medica
state: Sicilia
city: Firenze
country: Italy
facility: A.O. Careggi; Radioterapia
state: Toscana
city: Prato
country: Italy
facility: Ospedale Misericordia E Dolce; Oncologia Medica
state: Toscana
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia
state: Barcelona
city: Castellon de La Plana
country: Spain
facility: Hospital Provincial de Castellon; Servicio de Oncologia
state: Castellon
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia; Servicio de Oncologia
state: Cordoba
city: San Sebastian
country: Spain
facility: IInstituto Oncologico de San Sebastian, Oncologikoa; Servicio de Oncologia
state: Guipuzcoa
city: San Sebastian
country: Spain
facility: Hospital de Donostia; Servicio de Oncologia Medica
state: Guipuzcoa
city: Barcelona
country: Spain
facility: Hospital del Mar; Servicio de Oncologia
city: Caceres
country: Spain
facility: Hospital de San Pedro de Alcantara
city: La Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña (CHUAC, Materno Infantil), Oncología
city: La Coruña
country: Spain
facility: Centro Oncológico Gallego José Antonio Quiroga y Piñeiro, Servicio de Oncologia
city: Lerida
country: Spain
facility: Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario Clínico San Carlos; Servicio de Oncologia
city: Murcia
country: Spain
facility: Hospital Universitario Virgen de Arrixaca; Servicio de Oncologia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena; Servicio de Oncologia
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet; Servicio Oncologia
city: Ankara
country: Turkey
facility: Hacettepe Uni Medical Faculty Hospital; Oncology Dept
city: Ankara
country: Turkey
facility: Ankara City Hospital
city: Izmir
country: Turkey
facility: Ege Uni Medical Faculty Hospital; Oncology Dept
city: Malatya
country: Turkey
facility: Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department
city: Brighton
country: United Kingdom
facility: Brighton and Sussex Univ Hosp
city: Coventry
country: United Kingdom
facility: University Hospital coventry; Oncology Department
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: London
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Portsmouth
country: United Kingdom
facility: Queen Alexandra Hospital, Portsmouth
city: Scarborough
country: United Kingdom
facility: Scarborough General Hospital
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital; Cancer Clinical Trials Centre
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.