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

Breast Cancer Clinical Trial

— PERTAIN  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01491737
• Other study ID #: MO27775
• Secondary ID: 2011-002132-10
• Status: Completed
• Phase: Phase 2
• Start date: February 17, 2012
• Est. completion date: November 14, 2019

Study information

• Verified date: October 2020
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 258
• Est. completion date: November 14, 2019
• Est. primary completion date: March 17, 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Pertuzumab
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.
• Trastuzumab
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.
• Aromatase Inhibitor
Participants will receive 1 mg anastrozole or 2.5 mg letrozole orally once daily.
• Induction Chemotherapy
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.

Locations

Country	Name	City	State
Brazil	Hospital Perola Byington	Sao Paulo	SP
Brazil	Inst. Brasileiro de Controle Ao Cancer; Oncologia Clinica / Quimioterapia	Sao Paulo	SP
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP	Sao Paulo	SP
Brazil	Hospital Sao Jose	São Paulo	SP
France	HOPITAL JEAN MINJOZ; Oncologie	Besancon
France	Clinique Tivoli; Sce Radiotherapie	Bordeaux
France	Hopital Morvan; Oncologie - Radiotherapie	Brest
France	Centre Jean Perrin; Oncologie	Clermont Ferrand
France	Clinique De La Sauvegarde; Chimiotherapie	Lyon
France	Centre Catherine de Sienne; Chimiotherapie	Nantes
France	Centre Antoine Lacassagne; Hopital De Jour A2	Nice
France	CH De Senlis; Medecine 2	Senlis
France	Clinique Pasteur; Oncologie Medicale	Toulouse
France	Centre Alexis Vautrin; Oncologie Medicale	Vandoeuvre-les-nancy
India	Bangalore Institute of Oncology	Bangalore	Karnataka
India	Apollo Speciality Hospital	Chennai
India	Jaslok Hospital & Research Centre; Medical Oncology	Mumbai	Maharashtra
India	Indraprastha Apollo Hospitals	New Delhi	Delhi
India	Ruby Hall Clinic	Pune
Italy	Irccs Ist. Tumori Giovanni Paolo Ii; Dipartimento Oncologia Medica	Bari	Puglia
Italy	Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica	Bologna	Emilia-Romagna
Italy	Ospedale Antonio Perrino; Oncologia Medica	Brindisi	Puglia
Italy	Casa di Cura MultiMedica Ospedale di Castellanza; UO Senologia Medica	Castellanza	Lombardia
Italy	Az Ospedaliera Nuovo Garibaldi Quartiere Nesima; Oncologia Medica	Catania	Sicilia
Italy	A.O. Careggi; Radioterapia	Firenze	Toscana
Italy	Ospedale Vito Fazzi; Div. Oncoematologia	Lecce	Puglia
Italy	Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 1	Milano	Lombardia
Italy	Istituto Nazionale Tumori Fondazione G. Pascale	Napoli	Campania
Italy	Università degli Studi Federico II; Clinica di Oncologia Medica	Napoli	Campania
Italy	Ospedale Regionale Di Parma; Divisione Di Oncologia Medica	Parma	Emilia-Romagna
Italy	IRCCS Fondazione Maugeri; Oncologia Medica I	Pavia	Lombardia
Italy	A.O. Santa Maria Degli Angeli; U.O Di Oncologia Medica	Pordenone	Friuli-Venezia Giulia
Italy	Ospedale Misericordia E Dolce; Oncologia Medica	Prato	Toscana
Italy	Ospedale S.S. Trinità Nuovo; Divisione Oncologia	Sora	Lazio
Spain	Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia	Badalona	Barcelona
Spain	Hospital del Mar; Servicio de Oncologia	Barcelona
Spain	Hospital de San Pedro de Alcantara	Caceres
Spain	Hospital Provincial de Castellon; Servicio de Oncologia	Castellon de La Plana	Castellon
Spain	Hospital Universitario Reina Sofia; Servicio de Oncologia	Córdoba	Cordoba
Spain	Centro Oncológico Gallego José Antonio Quiroga y Piñeiro, Servicio de Oncologia	La Coruña
Spain	Complejo Hospitalario Universitario A Coruña (CHUAC, Materno Infantil), Oncología	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 de Donostia; Servicio de Oncologia Medica	San Sebastian	Guipuzcoa
Spain	IInstituto Oncologico de San Sebastian, Oncologikoa; Servicio de Oncologia	San Sebastian	Guipuzcoa
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
Turkey	Ankara City Hospital	Ankara
Turkey	Hacettepe Uni Medical Faculty Hospital; Oncology Dept	Ankara
Turkey	Ege Uni Medical Faculty Hospital; Oncology Dept	Izmir
Turkey	Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department	Malatya
United Kingdom	Brighton and Sussex Univ Hosp	Brighton
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	Queen Alexandra Hospital, Portsmouth	Portsmouth
United Kingdom	Scarborough General Hospital	Scarborough
United Kingdom	Weston Park Hospital; Cancer Clinical Trials Centre	Sheffield
United States	Georgia Cancer Specialists - Northside	Atlanta	Georgia
United States	Comprehensive Blood & CA Ctr; Research	Bakersfield	California
United States	Weinberg CA Inst Franklin Sq	Baltimore	Maryland
United States	Center For Cancer and Blood Disorders	Bethesda	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Ironwood Cancer TX & Rsch Ctrs	Chandler	Arizona
United States	Rocky Mountain Cancer Center - Denver	Denver	Colorado
United States	Genesis Cancer Center	Hot Springs	Arkansas
United States	Baylor College of Medicine; Lester & Sue Smith Breast Ctr	Houston	Texas
United States	NS-Long Island Jewish Hlth Sys	Lake Success	New York
United States	ProHEALTH Care Associates LLP	Lake Success	New York
United States	Northwest Georgia Oncology Centers, a Service of WellStar Cobb Hospital	Marietta	Georgia
United States	Crescent City Rsrch Cnsrtm, LLC	Marrero	Louisiana
United States	Advanced Medical Specialties	Miami	Florida
United States	Hematology Oncology Associates; Carol G. Simon Ctr	Morristown	New Jersey
United States	Norwalk Hospital	Norwalk	Connecticut
United States	UPMC Cancer Centers	Pittsburgh	Pennsylvania
United States	Washington University School of Medicine; Internal Medicine - Renal	Saint Louis	Missouri
United States	Scott and White Hospital; Cancer Center	Temple	Texas
United States	Cooper Hospital; Hematology & Oncology	Voorhees	New Jersey
United States	Cancer Center of Kansas	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Brazil,  France,  India,  Italy,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall Survival (OS)	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.	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	Overall Response Rate (ORR)	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.	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
Secondary	Clinical Benefit Rate (CBR)	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.	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
Secondary	Duration of Response (DOR)	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.	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	Time to Response (TTR)	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.	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
Secondary	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	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.	Baseline and every 3 cycles until treatment discontinuation (up to Cycle 120; 1 cycle is 21 days)
Secondary	Overview of the Number of Participants With Adverse Events, Severity Determined According to NCI-CTCAE Version 4.03	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.	From Baseline until the end of post-treatment follow-up (up to 89 months)
Secondary	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	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.	From Baseline until the end of post-treatment follow-up (up to 89 months)
Secondary	Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Values Over the Course of the Study	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.	Baseline and every 3 cycles until treatment discontinuation (up to Cycle 120; 1 cycle is 21 days)