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
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT01491737
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 258
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B: Trastuzumab + AI +/- Chemotherapy Aromatase Inhibitor 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. Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy Induction Chemotherapy 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. Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy Aromatase Inhibitor 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. Arm B: Trastuzumab + AI +/- Chemotherapy Induction Chemotherapy 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. Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy Pertuzumab 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. Arm A: Pertuzumab + Trastuzumab + AI +/- Chemotherapy Trastuzumab 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. Arm B: Trastuzumab + AI +/- Chemotherapy Trastuzumab 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.
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) 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 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.
- Secondary Outcome Measures
Name Time Method 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 survival (OS) was defined as the time from the date of randomization to the date of death, regardless of the cause of death. Participants who were alive at the time of the analysis were censored at the date of the last follow-up assessment. Participants without follow-up assessment were censored at the day of last study medication (pertuzumab, trastuzumab, AI or induction chemotherapy), and participants with no post-baseline information were censored at the date of randomization. The primary analysis of OS was planned to be performed at the same time as for PFS (when a total of 165 PFS events had occurred), and the final analysis was planned after at least 60 months follow-up for all participants.
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 Baseline and every 3 cycles until treatment discontinuation (up to Cycle 120; 1 cycle is 21 days) The EQ-5D VAS is a participant-rated questionnaire to assess health-related quality of life (QoL) in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state.
Overview of the Number of Participants With Adverse Events, Severity Determined According to NCI-CTCAE Version 4.03 From Baseline until the end of post-treatment follow-up (up to 89 months) All adverse events (AEs) occurring during the study and until the post-treatment safety follow-up visit approximately 28 days after last study medication were recorded; thereafter, only study drug-related serious adverse events (SAEs) continued to be collected. The investigator graded all AEs for severity per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03; if not listed, the AE was assessed as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening/disabling; Grade 5 = death. The investigator determined whether an AE was related to study drug and independently assessed severity and seriousness of each AE. AEs suggestive of congestive heart failure (CHF) were identified by the SMQ (wide) "Cardiac Failure" with a status of "serious", which included the preferred terms cardiac failure, left ventricular dysfunction, and pulmonary oedema.
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 Time to Response (TTR) was defined as the time from the date of randomization to the date of first complete response (CR) or partial response (PR). According to RECIST version 1.1, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm; PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. For participants who did not have a confirmed response, a censored TTR was calculated at the date of the last adequate tumor assessment. If no tumor assessment is performed for the participant (or all post-baseline assessments are not evaluable or PD) the censoring day would be set to day 1 (date of randomization). Analysis of this outcome measure was only planned to occur at the time of primary analysis.
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 From Baseline until the end of post-treatment follow-up (up to 89 months) The causes of death over the course of the study, regardless of whether the death was related to study treatment, are listed by preferred term according to the Medical Dictionary for Regulatory Activities (MedDRA), version 22.1.
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Values Over the Course of the Study Baseline and every 3 cycles until treatment discontinuation (up to Cycle 120; 1 cycle is 21 days) Left ventricular ejection fraction (LVEF) is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction. A normal LVEF ranges from 55% to 70%, as measured by echocardiogram or multiple-gated acquisition (MUGA) scan. All participants must have had a baseline LVEF of at least (≥)50% to enroll in the study; patients with clinically significant cardiovascular disease or baseline LVEF below 50% were not eligible for this study.
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 Duration of response (DOR) was defined as the period from the date of initial confirmed partial response (PR) or complete response (CR) until the date of progressive disease or death from any cause. According to RECIST version 1.1, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm; PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Participants with no documented progression after CR or PR were censored at the last date at which they were known to have had the CR or PR, respectively. The primary analysis of DOR was planned to be performed at the same time as for PFS (when a total of 165 PFS events had occurred), and the final analysis was planned after at least 60 months follow-up for all participants.
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 The overall response rate (ORR) was defined as the percentage of participants with best (confirmed) overall response (BOR) of either complete response (CR) or partial response (PR) from start of study treatment until progressive disease (PD)/recurrence or death, as assessed by the investigator according to RECIST version 1.1. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm; PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference baseline sum diameters; stable disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Participants needed to have two consecutive assessments of PR or CR at least 4 weeks apart to be a responder. Analysis of this outcome measure was only planned to occur at the time of primary analysis.
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 Clinical Benefit Rate (CBR) was defined as the percentage of participants with best (confirmed) partial response (PR) or complete response (CR) or stable disease (SD) for at least 6 months. According to RECIST version 1.1, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm; PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Analysis of this outcome measure was only planned to occur at the time of primary analysis.
Trial Locations
- Locations (82)
Ankara City Hospital
🇹🇷Ankara, Turkey
Washington University School of Medicine; Internal Medicine - Renal
🇺🇸Saint Louis, Missouri, United States
Ironwood Cancer TX & Rsch Ctrs
🇺🇸Chandler, Arizona, United States
Norwalk Hospital
🇺🇸Norwalk, Connecticut, United States
Georgia Cancer Specialists - Northside
🇺🇸Atlanta, Georgia, United States
Cancer Center of Kansas
🇺🇸Wichita, Kansas, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Weinberg CA Inst Franklin Sq
🇺🇸Baltimore, Maryland, United States
Rocky Mountain Cancer Center - Denver
🇺🇸Denver, Colorado, United States
Comprehensive Blood & CA Ctr; Research
🇺🇸Bakersfield, California, United States
NS-Long Island Jewish Hlth Sys
🇺🇸Lake Success, New York, United States
UPMC Cancer Centers
🇺🇸Pittsburgh, Pennsylvania, United States
Baylor College of Medicine; Lester & Sue Smith Breast Ctr
🇺🇸Houston, Texas, United States
Instituto do Cancer do Estado de Sao Paulo - ICESP
🇧🇷Sao Paulo, SP, Brazil
Scott and White Hospital; Cancer Center
🇺🇸Temple, Texas, United States
Inst. Brasileiro de Controle Ao Cancer; Oncologia Clinica / Quimioterapia
🇧🇷Sao Paulo, SP, Brazil
Clinique Tivoli; Sce Radiotherapie
🇫🇷Bordeaux, France
HOPITAL JEAN MINJOZ; Oncologie
🇫🇷Besancon, France
Clinique Pasteur; Oncologie Medicale
🇫🇷Toulouse, France
Centre Antoine Lacassagne; Hopital De Jour A2
🇫🇷Nice, France
Bangalore Institute of Oncology
🇮🇳Bangalore, Karnataka, India
Centre Alexis Vautrin; Oncologie Medicale
🇫🇷Vandoeuvre-les-nancy, France
Jaslok Hospital & Research Centre; Medical Oncology
🇮🇳Mumbai, Maharashtra, India
Università degli Studi Federico II; Clinica di Oncologia Medica
🇮🇹Napoli, Campania, Italy
Ospedale S.S. Trinità Nuovo; Divisione Oncologia
🇮🇹Sora, Lazio, Italy
Casa di Cura MultiMedica Ospedale di Castellanza; UO Senologia Medica
🇮🇹Castellanza, Lombardia, Italy
Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 1
🇮🇹Milano, Lombardia, Italy
A.O. Careggi; Radioterapia
🇮🇹Firenze, Toscana, Italy
Ospedale Misericordia E Dolce; Oncologia Medica
🇮🇹Prato, Toscana, Italy
Hospital Universitario Reina Sofia; Servicio de Oncologia
🇪🇸Córdoba, Cordoba, Spain
Hospital Provincial de Castellon; Servicio de Oncologia
🇪🇸Castellon de La Plana, Castellon, Spain
IInstituto Oncologico de San Sebastian, Oncologikoa; Servicio de Oncologia
🇪🇸San Sebastian, Guipuzcoa, Spain
Hospital de Donostia; Servicio de Oncologia Medica
🇪🇸San Sebastian, Guipuzcoa, Spain
Hospital del Mar; Servicio de Oncologia
🇪🇸Barcelona, Spain
Hospital de San Pedro de Alcantara
🇪🇸Caceres, Spain
Complejo Hospitalario Universitario A Coruña (CHUAC, Materno Infantil), Oncología
🇪🇸La Coruña, Spain
Centro Oncológico Gallego José Antonio Quiroga y Piñeiro, Servicio de Oncologia
🇪🇸La Coruña, Spain
Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Oncologia
🇪🇸Lerida, Spain
Hospital Ramon y Cajal; Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital Universitario Clínico San Carlos; Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital Universitario Virgen de Arrixaca; Servicio de Oncologia
🇪🇸Murcia, Spain
Hospital Universitario Virgen Macarena; Servicio de Oncologia
🇪🇸Sevilla, Spain
Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
🇪🇸Valencia, Spain
Hospital Universitario Miguel Servet; Servicio Oncologia
🇪🇸Zaragoza, Spain
Ege Uni Medical Faculty Hospital; Oncology Dept
🇹🇷Izmir, Turkey
Brighton and Sussex Univ Hosp
🇬🇧Brighton, United Kingdom
Queen Alexandra Hospital, Portsmouth
🇬🇧Portsmouth, United Kingdom
Scarborough General Hospital
🇬🇧Scarborough, United Kingdom
Weston Park Hospital; Cancer Clinical Trials Centre
🇬🇧Sheffield, United Kingdom
University Hospital coventry; Oncology Department
🇬🇧Coventry, United Kingdom
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
Queen Elizabeth Hospital
🇬🇧London, United Kingdom
Centre Jean Perrin; Oncologie
🇫🇷Clermont Ferrand, France
CH De Senlis; Medecine 2
🇫🇷Senlis, France
Genesis Cancer Center
🇺🇸Hot Springs, Arkansas, United States
Crescent City Rsrch Cnsrtm, LLC
🇺🇸Marrero, Louisiana, United States
Centre Catherine de Sienne; Chimiotherapie
🇫🇷Nantes, France
Advanced Medical Specialties
🇺🇸Miami, Florida, United States
A.O. Santa Maria Degli Angeli; U.O Di Oncologia Medica
🇮🇹Pordenone, Friuli-Venezia Giulia, Italy
Ospedale Antonio Perrino; Oncologia Medica
🇮🇹Brindisi, Puglia, Italy
Cooper Hospital; Hematology & Oncology
🇺🇸Voorhees, New Jersey, United States
Clinique De La Sauvegarde; Chimiotherapie
🇫🇷Lyon, France
Hopital Morvan; Oncologie - Radiotherapie
🇫🇷Brest, France
Irccs Ist. Tumori Giovanni Paolo Ii; Dipartimento Oncologia Medica
🇮🇹Bari, Puglia, Italy
Center For Cancer and Blood Disorders
🇺🇸Bethesda, Maryland, United States
Hospital Perola Byington
🇧🇷Sao Paulo, SP, Brazil
IRCCS Fondazione Maugeri; Oncologia Medica I
🇮🇹Pavia, Lombardia, Italy
Az Ospedaliera Nuovo Garibaldi Quartiere Nesima; Oncologia Medica
🇮🇹Catania, Sicilia, Italy
Ospedale Regionale Di Parma; Divisione Di Oncologia Medica
🇮🇹Parma, Emilia-Romagna, Italy
Apollo Speciality Hospital
🇮🇳Chennai, India
Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica
🇮🇹Bologna, Emilia-Romagna, Italy
Ospedale Vito Fazzi; Div. Oncoematologia
🇮🇹Lecce, Puglia, Italy
Hacettepe Uni Medical Faculty Hospital; Oncology Dept
🇹🇷Ankara, Turkey
Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department
🇹🇷Malatya, Turkey
ProHEALTH Care Associates LLP
🇺🇸Lake Success, New York, United States
Istituto Nazionale Tumori Fondazione G. Pascale
🇮🇹Napoli, Campania, Italy
Northwest Georgia Oncology Centers, a Service of WellStar Cobb Hospital
🇺🇸Marietta, Georgia, United States
Indraprastha Apollo Hospitals
🇮🇳New Delhi, Delhi, India
Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia
🇪🇸Badalona, Barcelona, Spain
Hematology Oncology Associates; Carol G. Simon Ctr
🇺🇸Morristown, New Jersey, United States
Ruby Hall Clinic
🇮🇳Pune, India
Hospital Sao Jose
🇧🇷São Paulo, SP, Brazil