Daily Everolimus in Combination With Trastuzumab and Vinorelbine in HER2/Neu Positive Women With Locally Advanced or Metastatic Breast Cancer (BOLERO-3)

A Randomized Phase III, Double-blind, Placebo-controlled Multicenter Trial of Daily Everolimus in Combination With Trastuzumab and Vinorelbine, in Pretreated Women With HER2/Neu Over-expressing Locally Advanced or Metastatic Breast Cancer.

This phase III, double-blind, placebo-controlled multinational study will assess the combination everolimus, vinorelbine, and trastuzumab compared to the combination vinorelbine and trastuzumab with respect to progressive-free survival and over survival in HER2/neu positive women with locally advanced or metastatic breast cancer who are resistant to trastuzumab and have been pre-treated with a taxane.

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer; HER2/Neu Over-expressing Locally Advanced Breast Cancer
• Intervention / Treatment: Drug: everolimus; Drug: vinorelbine; Drug: trastuzumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 569
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Cordoba, Argentina, X5002AOQ
    • Novartis Investigative Site
  • Tucuman, Argentina, T4000IAK
    • Novartis Investigative Site
  • Buenos Aires
    • C A B A, Buenos Aires, Argentina, C1019ABS
      • Novartis Investigative Site
    • Caba, Buenos Aires, Argentina, C1050AAK
      • Novartis Investigative Site
    • Mar del Plata, Buenos Aires, Argentina, 7600
      • Novartis Investigative Site
    • Quilmes, Buenos Aires, Argentina, B1878DVB
      • Novartis Investigative Site
  • Misiones
    • Posadas, Misiones, Argentina
      • Novartis Investigative Site
  • Sante Fe
    • Rosario, Sante Fe, Argentina, S200KZE
      • Novartis Investigative Site
  • Viedma
    • Rio Negro, Viedma, Argentina, 8500
      • Novartis Investigative Site
• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • Novartis Investigative Site
    • St. Leonards, New South Wales, Australia, 2065
      • Novartis Investigative Site
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Novartis Investigative Site
    • Southport, Queensland, Australia, 4215
      • Novartis Investigative Site
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Novartis Investigative Site
  • Victoria
    • East Bentleigh, Victoria, Australia, 3165
      • Novartis Investigative Site
• Belgium
  • Brussel, Belgium, 1090
    • Novartis Investigative Site
  • Bruxelles, Belgium, 1000
    • Novartis Investigative Site
  • Liège, Belgium, 4000
    • Novartis Investigative Site
  • Namur, Belgium, 5000
    • Novartis Investigative Site
  • Sint-Niklaas, Belgium, 9100
    • Novartis Investigative Site
• China
  • Beijing, China, 100021
    • Novartis Investigative Site
  • Beijing, China, 100039
    • Novartis Investigative Site
  • Guangzhou, China, 510060
    • Novartis Investigative Site
  • Shanghai, China, 200025
    • Novartis Investigative Site
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Novartis Investigative Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Novartis Investigative Site
• Czech Republic
  • Novy Jicin, Czech Republic, 741 01
    • Novartis Investigative Site
  • Olomouc, Czech Republic, 775 20
    • Novartis Investigative Site
  • Prague 5, Czech Republic, 150 00
    • Novartis Investigative Site
• France
  • Bayonne, France, 64100
    • Novartis Investigative Site
  • Besançon cedex, France, 25030
    • Novartis Investigative Site
  • Hyères, France, 83400
    • Novartis Investigative Site
  • La Chaussée St Victor, France, 41260
    • Novartis Investigative Site
  • La Roche sur Yon Cedex, France, 85925
    • Novartis Investigative Site
  • Nice Cedex 2, France, 06189
    • Novartis Investigative Site
  • Saint-Brieuc Cédex, France, 22015
    • Novartis Investigative Site
  • Villejuif Cedex, France, 94805
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 14195
    • Novartis Investigative Site
  • Frankfurt, Germany, 60590
    • Novartis Investigative Site
  • Gerlingen, Germany, 70839
    • Novartis Investigative Site
  • Halle/Saale, Germany, 06120
    • Novartis Investigative Site
  • Hamburg, Germany, 20249
    • Novartis Investigative Site
  • Homburg, Germany, 66421
    • Novartis Investigative Site
  • Kiel, Germany, 24105
    • Novartis Investigative Site
  • Magdeburg, Germany, 39108
    • Novartis Investigative Site
  • Mainz, Germany, 55131
    • Novartis Investigative Site
  • Minden, Germany, 32429
    • Novartis Investigative Site
  • München, Germany, 80638
    • Novartis Investigative Site
  • Recklinghausen, Germany, 45657
    • Novartis Investigative Site
  • Velbert, Germany, 42551
    • Novartis Investigative Site
• Greece
  • Athens, Greece, 18547
    • Novartis Investigative Site
  • Heraklion Crete, Greece, 711 10
    • Novartis Investigative Site
  • GR
    • Athens, GR, Greece, 151 23
      • Novartis Investigative Site
    • Patra - RIO, GR, Greece, 265 04
      • Novartis Investigative Site
    • Thessaloniki, GR, Greece, 546 45
      • Novartis Investigative Site
    • Thessaloniki, GR, Greece, 564 03
      • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, H-1122
    • Novartis Investigative Site
  • Budapest, Hungary, 1062
    • Novartis Investigative Site
  • Debrecen, Hungary, 4032
    • Novartis Investigative Site
  • Gyor, Hungary, H-9023
    • Novartis Investigative Site
• Israel
  • Jerusalem, Israel, 9112001
    • Novartis Investigative Site
  • Petach Tikva, Israel, 49100
    • Novartis Investigative Site
  • Ramat Gan, Israel, 5266202
    • Novartis Investigative Site
  • Tel Aviv, Israel, 6423906
    • Novartis Investigative Site
• Italy
  • CT
    • Catania, CT, Italy, 95125
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20133
      • Novartis Investigative Site
    • Milano, MI, Italy, 20132
      • Novartis Investigative Site
    • Milano, MI, Italy, 20157
      • Novartis Investigative Site
  • PV
    • Pavia, PV, Italy, 27100
      • Novartis Investigative Site
  • SO
    • Sondrio, SO, Italy, 23100
      • Novartis Investigative Site
• Japan
  • Fukuoka, Japan, 811-1395
    • Novartis Investigative Site
  • Osaka, Japan, 540-0006
    • Novartis Investigative Site
  • Osaka, Japan, 537-8511
    • Novartis Investigative Site
  • Aichi
    • Nagoya, Aichi, Japan, 464-8681
      • Novartis Investigative Site
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • Novartis Investigative Site
  • Gunma
    • Maebashi-city, Gunma, Japan, 371-8511
      • Novartis Investigative Site
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 003-0804
      • Novartis Investigative Site
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 241-8515
      • Novartis Investigative Site
  • Kumamoto
    • Kumamoto City, Kumamoto, Japan, 860-8556
      • Novartis Investigative Site
  • Kyoto
    • Kyoto-city, Kyoto, Japan, 606-8507
      • Novartis Investigative Site
  • Osaka
    • Suita-city, Osaka, Japan, 565-0871
      • Novartis Investigative Site
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8431
      • Novartis Investigative Site
    • Koto, Tokyo, Japan, 135-8550
      • Novartis Investigative Site
• Mexico
  • Distrito Federal
    • Ciudad De Mexico, Distrito Federal, Mexico, 04980
      • Novartis Investigative Site
  • Guanajuato
    • León, Guanajuato, Mexico, 37000
      • Novartis Investigative Site
• Poland
  • Lublin, Poland, 20-090
    • Novartis Investigative Site
  • Warszawa, Poland, 02-781
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 169610
    • Novartis Investigative Site
• Slovakia
  • Bratislava, Slovakia, 83310
    • Novartis Investigative Site
  • Kosice, Slovakia, 040 91
    • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08041
    • Novartis Investigative Site
  • Madrid, Spain, 28034
    • Novartis Investigative Site
  • Madrid, Spain, 28007
    • Novartis Investigative Site
  • Madrid, Spain, 28040
    • Novartis Investigative Site
  • Zaragoza, Spain, 50009
    • Novartis Investigative Site
  • Andalucia
    • Cordoba, Andalucia, Spain, 14004
      • Novartis Investigative Site
    • Jaen, Andalucia, Spain, 23007
      • Novartis Investigative Site
    • Sevilla, Andalucia, Spain, 41014
      • Novartis Investigative Site
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08036
      • Novartis Investigative Site
  • Comunidad Valenciana
    • Valencia, Comunidad Valenciana, Spain, 46009
      • Novartis Investigative Site
  • Galicia
    • A Coruna, Galicia, Spain, 15009
      • Novartis Investigative Site
    • La Coruna, Galicia, Spain, 15006
      • Novartis Investigative Site
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Novartis Investigative Site
  • Santa Cruz de Tenerife
    • La Laguna, Santa Cruz de Tenerife, Spain, 38320
      • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10330
    • Novartis Investigative Site
  • Bangkok, Thailand, 10400
    • Novartis Investigative Site
  • Songkla, Thailand, 90110
    • Novartis Investigative Site
• Turkey
  • Ankara, Turkey, 06100
    • Novartis Investigative Site
  • Fatih / Istanbul, Turkey, 34098
    • Novartis Investigative Site
  • Izmir, Turkey, 35040
    • Novartis Investigative Site
• United Kingdom
  • Bournemouth, United Kingdom, BH7 7DW
    • Novartis Investigative Site
  • Leeds, United Kingdom, LS9 7TF
    • Novartis Investigative Site
  • London, United Kingdom, EC1A 7BE
    • Novartis Investigative Site
  • Manchester, United Kingdom, M20 4BX
    • Novartis Investigative Site
  • Plymouth, United Kingdom, PL6 8DH
    • Novartis Investigative Site
  • Cornwall
    • Truro, Cornwall, United Kingdom, TR1 3LJ
      • Novartis Investigative Site
  • England
    • Surrey, England, United Kingdom, GU2 7XX
      • Novartis Investigative Site
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona / Cancer Center AZ Onc Assoc
    • Tucson, Arizona, United States, 85724
      • University of Arizona / Cancer Center Deptof Uof A/Arizona Cancer(3)
  • California
    • La Jolla, California, United States, 92093-0658
      • University of California San Diego - Moores Cancer Center La Jolla - UCSD Moores Cancer
  • Colorado
    • Greenwood Village, Colorado, United States
      • Rocky Mountain Cancer Centers RMCC
  • District of Columbia
    • Washington, District of Columbia, United States, 20007-2197
      • Georgetown University/Lombardi Cancer Center Dept.of Lombardi CancerCtr (3)
  • Florida
    • Boca Raton, Florida, United States, 33248
      • Comprehensive Cancer Center - Boca Raton Deerfield Beach
    • Boca Raton, Florida, United States, 33248
      • Comprehensive Cancer Center - Boca Raton Dept.of BocaRatonCompCanCtr
    • Fort Myers, Florida, United States, 33916
      • Florida Cancer Specialists DeptofFloridaCancerSpecialists
    • Hollywood, Florida, United States, 33021
      • Memorial Hospital Memorial Cancer Institute
    • Orlando, Florida, United States, 32806
      • MD Anderson Cancer Center - Orlando Dept.ofMDACC-Orlando(2)
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine/Winship Cancer Institute Dept.of WinshipCancerInst. (2)
  • Illinois
    • Evanston, Illinois, United States, 60201
      • North Shore University Health System NSU
  • Kansas
    • Overland Park, Kansas, United States, 66210
      • Kansas City Cancer Center KCCC- South (2)
  • Maryland
    • Owning Mills, Maryland, United States, 21117,
      • Maryland Oncology Hematology
  • Minnesota
    • St. Louis Park, Minnesota, United States, 55416
      • Park Nicollet Institute Dept. of Park Nicollet
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • St. Louis University Cancer Center SLU Cancer Center
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center Unv Nebraska Med Ctr (2)
  • Nevada
    • Las Vegas, Nevada, United States, 89135
      • Nevada Cancer Institute Dept. of Nevada Cancer (3)
    • Las Vegas, Nevada, United States, 89109
      • Comprehensive Cancer Centers of Nevada CCC of Nevada Henderson (4)
  • New Jersey
    • Summit, New Jersey, United States, 07901
      • Overlook Hospital - Carol G Simon Cancer Center Carol G Simon
  • New York
    • Lake Success, New York, United States, 11042
      • Clinical Research Alliance Dept.ofArenaOncologyAssoc(2)
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center Dept. of DUMC (2)
  • Oregon
    • Portland, Oregon, United States, 97210
      • Northwest Cancer Specialists Tutlatin
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Cancer Institute DeptofMageeWomen'sHospital(2)
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • The Jones Clinic Dept .of The Jones Clinic (3)
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute Dept.ofSarahCannonCancerCtr(6)
  • Texas
    • Dallas, Texas, United States, 75246
      • Texas Oncology Texas Oncology - Sammons
    • Dallas, Texas, United States, 75246
      • Texas Oncology Texas Onc - Amarillo
    • Dallas, Texas, United States, 75230
      • Texas Cancer Center ( Medical City Dallas Hospital) Dept. of Texas Cancer Ctr. (2)
    • Dallas, Texas, United States, 75246
      • Texas Oncology Presbyterian Hospital (2)
    • Dallas, Texas, United States, 75251
      • Texas Oncology Midtown
    • Dallas, Texas, United States, 75390-8852
      • University of Texas Southwestern Medical Center University of TX SW Med Ctr(2)
    • Houston, Texas, United States, 77030-4009
      • University of Texas/MD Anderson Cancer Center SC-5
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine Baylor
    • Longview, Texas, United States, 75601
      • Longview Cancer Center Longview Cancer Center (2)
    • San Antonio, Texas, United States, 78258
      • South Texas Oncology and Hematology, PA South Texas Oncology (2)
    • San Antonio, Texas, United States, 78229
      • Cancer Care Centers of South Texas / HOAST CCC of So. TX- San Antonio(2)
    • Tyler, Texas, United States, 75702
      • Tyler Cancer Center Dept.ofTylerCancerCtr. (2)
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists Utah Cancer (2)
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists Fairfax No.VA (2)
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates Dept. of VOA (2)
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute Swedish Cancer Institute
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54301
      • Green Bay Oncology Green Bay Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Histologically or cytologically confirmed invasive breast carcinoma with locally recurrent or radiological evidence of metastatic disease. Locally recurrent disease must not be amenable to resection with curative intent.
• HER2+ status defined as IHC 3+ staining or in situ hybridization positive
• Patients with resistance to trastuzumab
• Prior taxane therapy
• Patients with an ECOG performance status of 0 - 2
• Patients with measurable disease as per RECIST criteria
• Documentation of negative pregnancy test for patients of child bearing potential prior to enrollment within 7 days prior to randomization. Sexually active pre-menopausal women must use adequate contraceptive measures, excluding estrogen containing contraceptives, while on study;
• Patients must meet laboratory criteria defined in the study within 21 days prior to randomization

Exclusion Criteria:

• Prior mTOR inhibitors or vinca alkaloid agents for the treatment of cancer
• More than three prior chemotherapy lines for advanced disease.
• Symptomatic CNS metastases or evidence of leptomeningeal disease. Previously treated asymptomatic CNS metastases are allowed provided that the last treatment for CNS metastases was completed >8 weeks prior to randomization
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus
• Peripheral neuropathy ≥ grade 2 at randomization
• Active cardiac disease
• History of cardiac dysfunction
• Any malignancy within 5 years prior to randomization, with the exception of adequately treated in-situ carcinoma of the cervix uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer
• Known hypersensitivity to any study medication
• Breastfeeding or pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Everolimus + vinorelbine + trastuzumab; Oral everolimus (5 mg/day) + intravenous vinorelbine (25 mg/m2 weekly) + intravenous trastuzumab (2 mg/kg weekly following a 4 mg/kg loading dose on Day 1 of Cycle 1 only)	Drug: everolimus; Oral everolimus was taken once 5 mg/day (2 × 2.5 mg tablets) and were packaged into blister packs.; Other Names: RAD001; Drug: vinorelbine; intravenous vinorelbine (25 mg/m2 weekly); Drug: trastuzumab; intravenous trastuzumab (2 mg/kg weekly following a 4 mg/kg loading dose on Day 1 of Cycle 1 only)
PLACEBO_COMPARATOR: placebo + vinorelbine + trastuzumab; Oral daily matching placebo + intravenous vinorelbine (25 mg/m2 weekly) + intravenous trastuzumab (2 mg/kg weekly following a 4 mg/kg loading dose on Day 1 of Cycle 1 only	Drug: vinorelbine; intravenous vinorelbine (25 mg/m2 weekly); Drug: trastuzumab; intravenous trastuzumab (2 mg/kg weekly following a 4 mg/kg loading dose on Day 1 of Cycle 1 only); Drug: Placebo; Oral everolimus placebo was taken once 5 mg/day (2 × 2.5 mg tablets) and were packaged into blister packs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progressive-free Survival (PFS) Per Investigator Assessment	PFS was defined as the time from the date of randomization to the date of first radiologically documented tumor progression or death from any cause, whichever occurs first. PFS primary analysis performed when 415 events were reached. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	Every 6 weeks until disease progression or death which ever occurred first up to about 41 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS was defined as the time from date of randomization to the date of death from any cause. Final OS was conducted when 388 deaths occurred.	Every 3 months until death up to 41 months
Overall Response Rate (ORR)	ORR was defined as the percentage of participants whose best overall response was either complete response (CR) or partial response (PR) according to RECIST version 1.0. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	Every 6 weeks until disease progression or death which ever occurred first up to about 41 months
Clinical Benefit Rate (CBR)	CBR was defined as the percentage of participants whose best overall response, according to RECIST, was either complete response (CR), a partial response (PR) or stable disease (SD) lasting for at least 24 weeks. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; SD = Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD; PD = At least a 20% increase in the sum of the longest diameter of all measured target lesions, taking as reference the smallest sum of longest diameter of all target lesions recorded at or after baseline.	Every 6 weeks until disease progression or death which ever occurred first up to about 41 months
Median Time to Deterioration of the ECOG Performance Status Score	Time to deterioration of ECOG performance status score was summarized at time of assessment. ECOG (Eastern Cooperative Oncology Group)performance scale is a standard criteria for measuring how treatment of cancer impacts their level of functioning in terms of their ability to care for themselves, daily activity, & physical ability (walking, working, etc.). Scale score ranges from 0 to 5, 5 being the worst. ECOG scale index: 0 - Fully active, able to carry on all pre-disease performance without restriction. 1 - Restricted in physically strenuous activity but ambulatory & able to carry out work of a light or sedentary nature, e.g., light housework, office work. 2 - Ambulatory & capable of all self-care but unable to carry out any work activities. Up & about more than 50% of waking hours. 3 - Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4 - Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5 - Dead	baseline, until disease progression or death up to about 41 months
PRO: Time to Deterioration in Global Health Status/QoL Domain Score of the European Organization for the Research and Treatment of Cancer (EORTC)-Core Quality of Life Questionnaire (QLQ-C30) (by at Least 10%)	PRO = patient reported outcomes; Time to deterioration (≥ 10% worsening from baseline), in the global health status of EORTC QLQ-C30 scale was done in the 3 functional scales (emotional, physical, & social functioning [EF, PF, & SF]). It contains 30 items & is composed of multi-item scales & single-item measures. These include 5 functional scales (physical, role, emotional, social & cognitive functioning), 3 symptom scales (fatigue, pain, nausea, & vomiting), a global health status/QoL scale, and 6 single items (dyspnea, diarrhea, constipation, anorexia, insomnia & financial impact). Each of the multi-item scale includes a different set of items - no item occurs in more than 1 scale. Each item in the EORTC QLQ-C30 has 4 response categories (1=Not at all, 2= A little, 3= Quite a bit, 4= Very much) with the higher number representing a worse outcome. The global health domain score of the QLQ-C30 questionnaire was pre-specified as the primary QoL domain of interest & disclosed here.	Baseline, until disease progression or death up to about 41 months
Everolimus Blood Concentrations by Leading Dose and Time Point	Pre-dose (Cmin) and 2 hours post-dose (C2h) everolimus PK blood samples were collected at Cycle 2 Day 1. Only valid everolimus PK blood samples collected at steady state were used in the analyses.	Cycle 2, Day 1
Vinorelbine Blood Concentrations by Leading Dose and Time Point	Pre-infusion (Cmin) and end of infusion (C2h) vinorelbine PK blood samples were collected at Cycle 2 Day 1. Only valid vinorelbine PK blood samples collected at steady state were used in the analyses.	Cycle 2, Day 1
Trastuzumab Blood Concentrations by Leading Dose and Time Point	Pre-infusion (Cmin) and end of infusion (C2h) trastuzumab PK blood samples were collected at Cycle 3 Day 1. Only valid trastuzumab PK blood samples collected at steady state were used in the analyses.	Cycle 3, Day 1

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Andre F, O'Regan R, Ozguroglu M, Toi M, Xu B, Jerusalem G, Masuda N, Wilks S, Arena F, Isaacs C, Yap YS, Papai Z, Lang I, Armstrong A, Lerzo G, White M, Shen K, Litton J, Chen D, Zhang Y, Ali S, Taran T, Gianni L. Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2014 May;15(6):580-91. doi: 10.1016/S1470-2045(14)70138-X. Epub 2014 Apr 14.

Helpful Links

• Visit BOLERO-3 NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (ACTUAL): June 1, 2015
• Study Completion (ACTUAL): June 1, 2015

Study Registration Dates

• First Submitted: November 2, 2009
• First Submitted That Met QC Criteria: November 3, 2009
• First Posted (ESTIMATE): November 4, 2009

Study Record Updates

• Last Update Posted (ACTUAL): April 5, 2017
• Last Update Submitted That Met QC Criteria: February 20, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Breast cancer; trastuzumab; Metastatic breast cancer; everolimus; herceptin; RAD001; vinorelbine; locally advanced breast cancer; HER2/neu positive breast cancer; HER2/neu over-expressing; progressive-free survival (PFS); over survival (OS); bolero; bolero 3; HER+
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Trastuzumab; Vinorelbine; Everolimus
• Other Study ID Numbers: CRAD001W2301; 2008-008697-31 (EUDRACT_NUMBER)