Everolimus in Combination With Trastuzumab and Paclitaxel in the Treatment of HER2 Positive Locally Advanced or Metastatic Breast Cancer (BOLERO-1)

A Randomized Phase III, Double-Blind, Placebo-Controlled Multicenter Trial of Everolimus in Combination With Trastuzumab and Paclitaxel, as First Line Therapy in Women With HER2 Positive Locally Advanced or Metastatic Breast Cancer

The purpose of this Phase III study was to confirm the value of adding everolimus to weekly paclitaxel and trastuzumab as treatment of HER2-overexpressing metastatic breast cancer.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Everolimus; Drug: Trastuzumab; Drug: Paclitaxel; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 719
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Capital Federal, Argentina, 1417
    • Novartis Investigative Site
  • Cordoba, Argentina, X5004BAL
    • Novartis Investigative Site
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1050AAK
      • Novartis Investigative Site
    • Mar del Plata, Buenos Aires, Argentina, B7600CTO
      • 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
  • Queensland
    • Southport, Queensland, Australia, 4215
      • Novartis Investigative Site
  • Victoria
    • East Bentleigh, Victoria, Australia, 3165
      • Novartis Investigative Site
• Belgium
  • Charleroi, Belgium, 6000
    • Novartis Investigative Site
  • Hasselt, Belgium, 3500
    • Novartis Investigative Site
  • Verviers, Belgium, 4800
    • Novartis Investigative Site
  • Wilrijk, Belgium, 2610
    • Novartis Investigative Site
  • Yvoir, Belgium, 5530
    • Novartis Investigative Site
• Brazil
  • MG
    • Belo Horizonte, MG, Brazil, 30130-100
      • Novartis Investigative Site
    • Belo Horizonte, MG, Brazil, 30380-490
      • Novartis Investigative Site
  • RJ
    • Rio de Janeiro, RJ, Brazil, 20230-130
      • Novartis Investigative Site
  • SP
    • Sao Paulo, SP, Brazil, 01246 000
      • Novartis Investigative Site
    • São Paulo, SP, Brazil, 04038-001
      • Novartis Investigative Site
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2W 1S6
      • Novartis Investigative Site
    • Montreal, Quebec, Canada, H4J 1C5
      • Novartis Investigative Site
    • St-Jerome, Quebec, Canada, J7Z 5T3
      • 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
  • Guangdong
    • Guangzhou, Guangdong, China, 51000
      • Novartis Investigative Site
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Novartis Investigative Site
  • Jiangsu
    • Nanjing, Jiangsu, China, 210002
      • Novartis Investigative Site
    • Nanjing, Jiangsu, China, 210009
      • Novartis Investigative Site
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Novartis Investigative Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Novartis Investigative Site
• Colombia
  • Bogota, Colombia
    • Novartis Investigative Site
  • Florida Blanca, Colombia
    • Novartis Investigative Site
  • Monteria, Colombia
    • Novartis Investigative Site
  • Cundinamarca
    • Bogota, Cundinamarca, Colombia, 0000
      • Novartis Investigative Site
• Egypt
  • Alexandria, Egypt
    • Novartis Investigative Site
  • Cairo, Egypt
    • Novartis Investigative Site
• France
  • Limoges, France, 87000
    • Novartis Investigative Site
  • Rouen, France, 76000
    • Novartis Investigative Site
  • Saint-Herblain Cédex, France, 44805
    • Novartis Investigative Site
  • Strasbourg Cedex, France, F 67098
    • Novartis Investigative Site
  • Thonon-les-Bains Cedex, France, 74203
    • Novartis Investigative Site
  • Toulouse Cedex 9, France, 31059
    • Novartis Investigative Site
  • Villejuif Cedex, France, 94805
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 10098
    • Novartis Investigative Site
  • Chemnitz, Germany, 09113
    • Novartis Investigative Site
  • Esslingen, Germany, 73730
    • Novartis Investigative Site
  • Kiel, Germany, 24105
    • Novartis Investigative Site
  • Muenster, Germany, 48149
    • Novartis Investigative Site
• Greece
  • Athens, Greece, 18547
    • Novartis Investigative Site
  • Athens, Greece, 115 28
    • Novartis Investigative Site
  • Heraklion Crete, Greece, 711 10
    • Novartis Investigative Site
  • GR
    • Athens, GR, Greece, 151 23
      • Novartis Investigative Site
    • Thessaloniki, GR, Greece, 564 03
      • Novartis Investigative Site
• Hong Kong
  • Hong Kong SAR, Hong Kong
    • Novartis Investigative Site
  • Shatin, New Territories, Hong Kong
    • Novartis Investigative Site
  • Tuen Mun, Hong Kong
    • Novartis Investigative Site
• Ireland
  • Dublin 4, Ireland
    • Novartis Investigative Site
  • Dublin 8, Ireland
    • Novartis Investigative Site
  • Dublin 9, Ireland
    • Novartis Investigative Site
  • Cork
    • Wilton, Cork, Ireland
      • Novartis Investigative Site
• Italy
  • Napoli, Italy, 80131
    • Novartis Investigative Site
  • MB
    • Monza, MB, Italy, 20900
      • Novartis Investigative Site
  • MO
    • Modena, MO, Italy, 41124
      • Novartis Investigative Site
  • PD
    • Camposampiero, PD, Italy, 35012
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00128
      • Novartis Investigative Site
• Japan
  • 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
  • Fukuoka
    • Fukuoka-city, Fukuoka, Japan, 811-1395
      • Novartis Investigative Site
    • Kitakyushu, Fukuoka, Japan, 802-0077
      • Novartis Investigative Site
  • Gunma
    • Maebashi city, Gunma, Japan, 371 8511
      • Novartis Investigative Site
  • Hokkaido
    • Sapporo city, Hokkaido, Japan, 060 8648
      • Novartis Investigative Site
  • Kanagawa
    • Isehara-city, Kanagawa, Japan, 259-1193
      • Novartis Investigative Site
  • Kumamoto
    • Kumamoto City, Kumamoto, Japan, 860-8556
      • Novartis Investigative Site
  • Kyoto
    • Sakyo-ku, Kyoto, Japan, 606 8507
      • Novartis Investigative Site
  • Osaka
    • Osaka-city, Osaka, Japan, 540-0006
      • Novartis Investigative Site
    • Suita-city, Osaka, Japan, 565 0871
      • Novartis Investigative Site
  • Saitama
    • Kitaadachi-gun, Saitama, Japan, 362-0806
      • Novartis Investigative Site
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8677
      • Novartis Investigative Site
    • Chuo-ku, Tokyo, Japan, 104-8560
      • Novartis Investigative Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 02841
    • Novartis Investigative Site
  • Korea
    • Gyeonggi-do, Korea, Korea, Republic of, 10408
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 06351
      • Novartis Investigative Site
• Lebanon
  • Ashrafieh, Lebanon, 166830
    • Novartis Investigative Site
  • Beirut, Lebanon, 1107 2020
    • Novartis Investigative Site
• Mexico
  • Distrito Federal
    • Ciudad De Mexico, Distrito Federal, Mexico, 04980
      • Novartis Investigative Site
  • Veracruz
    • Zaragoza, Veracruz, Mexico, 91910
      • Novartis Investigative Site
• Peru
  • Lima
    • San Borja, Lima, Peru, 41
      • Novartis Investigative Site
    • Surquillo, Lima, Peru, 34
      • Novartis Investigative Site
• Puerto Rico
  • San Juan, Puerto Rico, 00921
    • San Juan VA Hospital San Juan Hospital
• Russian Federation
  • Moscow, Russian Federation, 115478
    • Novartis Investigative Site
  • Moscow, Russian Federation, 143423
    • Novartis Investigative Site
  • Moscow, Russian Federation, 129128
    • Novartis Investigative Site
  • St Petersburg, Russian Federation, 197758
    • Novartis Investigative Site
  • St. Petersburg, Russian Federation, 198255
    • Novartis Investigative Site
  • Tatarstan Republic
    • Kazan, Tatarstan Republic, Russian Federation, 420029
      • Novartis Investigative Site
• South Africa
  • Bloemfontein, South Africa, 9301
    • Novartis Investigative Site
  • Durban, South Africa, 4091
    • Novartis Investigative Site
  • Pretoria, South Africa, 0002
    • Novartis Investigative Site
• Switzerland
  • Genève, Switzerland, 1211
    • Novartis Investigative Site
  • Zuerich, Switzerland, 8038
    • Novartis Investigative Site
• Taiwan
  • Kaohsiung, Taiwan, 80756
    • Novartis Investigative Site
  • Taichung, Taiwan, 40447
    • Novartis Investigative Site
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
  • Taoyuan, Taiwan, 33305
    • Novartis Investigative Site
  • Taiwan, ROC
    • Taipei, Taiwan, ROC, Taiwan, 11217
      • Novartis Investigative Site
• Turkey
  • Altunizade, Turkey, 34662
    • Novartis Investigative Site
  • Ankara, Turkey, 06100
    • Novartis Investigative Site
  • Izmir, Turkey, 35040
    • Novartis Investigative Site
  • Izmir, Turkey, 35340
    • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • Novartis Investigative Site
  • Sutton, United Kingdom, SM2 5PT
    • Novartis Investigative Site
  • Cornwall
    • Truro, Cornwall, United Kingdom, TR1 3LJ
      • Novartis Investigative Site
• United States
  • Alabama
    • Mobile, Alabama, United States, 36688
      • University of South Alabama / Mitchell Cancer Institute Dept. of Mitchell Cancer Inst.
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Ironwood Cancer and Research Centers
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group
  • California
    • Bakersfield, California, United States, 93309
      • Comprehensive Blood and Cancer Center Dept. of CBCC (2)
    • Fullerton, California, United States, 92835
      • St. Jude Heritage Medical Group Virginia Crosson Cancer Center
    • Los Angeles, California, United States, 90095
      • University of California at Los Angeles Dept. of UCLA
    • Oxnard, California, United States, 93030
      • Ventura County Hematology and Oncology
    • Redondo Beach, California, United States, 90277
      • Cancer Care Associates Medical Group Dept. of CCA
    • Santa Barbara, California, United States, 93105
      • Santa Barbara Hematolgy Oncology Medical Group Dept.ofSantaBarbaraHem/Onc
    • Santa Maria, California, United States, 93454
      • Central Coast Medical Oncology Corporation Onc Dept
  • Colorado
    • Greenwood Village, Colorado, United States
      • Rocky Mountain Cancer Centers RMCC - Denver-Midtown (3)
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists Dept.of FloridaCancerSpec. (2)
    • West Palm Beach, Florida, United States, 33401
      • Florida Cancer Specialists
  • Indiana
    • Indianapolis, Indiana, United States, 46227
      • Central Indiana Cancer Centers CICC - East (3)
  • Kansas
    • Overland Park, Kansas, United States, 66210
      • Kansas City Cancer Center Dept. of KCCC
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center Unv Nebraska Med Ctr (2)
  • New York
    • Albany, New York, United States, 12208
      • New York Oncology Hematology NYOH Amsterdam
    • New York, New York, United States, 10003
      • Beth Israel Medical Center Dept.ofBeth Israel Med. Ctr(2)
  • Oregon
    • Portland, Oregon, United States, 97210
      • Northwest Cancer Specialists Vancouver Cancer Center (3)
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute Dept.ofSarahCannonCancerCtr(5)
  • Texas
    • Dallas, Texas, United States, 75246
      • Texas Oncology Charles A. Sammons Cancer Ctr
    • Dallas, Texas, United States, 75251
      • Texas Oncology P A SC-Austin
    • Tyler, Texas, United States, 75702
      • Tyler Cancer Center Dept.ofTylerCancerCtr. (2)
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates SC
    • Richmond, Virginia, United States, 23230
      • Virginia Cancer Institute VCI (3)
• Venezuela
  • Estado Carabobo
    • Valencia, Estado Carabobo, Venezuela, 2001
      • Novartis Investigative Site

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:

• Adult Women (≥ 18 years old).
• Histologically or cytologically confirmed invasive breast carcinoma with local recurrence or radiological evidence of metastatic disease.
• Must have at least one lesion that can be accurately measured or bone lesions in the absence of measurable disease.
• HER2+ patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive).
• Prior trastuzumab and/or chemotherapy (taxanes included) as neo-adjuvant or adjuvant treatment is allowed but should be discontinued > 12 months prior to randomization.
• Prior treatment for breast cancer with endocrine therapy (adjuvant or metastatic settings) is allowed but should be discontinued at randomization. Patients treated with bisphosphonates at entry or who start bisphosphonates during study may continue this therapy during protocol treatment.
• Documentation of negative pregnancy test.
• Organ functions at time of inclusion.

Exclusion Criteria:

• Prior mTOR inhibitors for the treatment of cancer.
• Other anticancer therapy for locally advanced or metastatic breast cancer except for prior hormonal therapy.
• Patients with only non-measurable lesions other than bone metastasis (e.g. pleural effusion, ascites, etc).
• Radiotherapy to ≥ 25% of the bone marrow within 4 weeks prior to randomization
• History of central nervous system metastasis.
• Impairment of gastrointestinal (GI) function or GI disease or active ulceration of the upper gastrointestinal tract.
• Serious peripheral neuropathy.
• Cardiac disease or dysfunction.
• Uncontrolled hypertension.
• HIV.
• Pregnant,

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Everolimus + Paclitaxel + Trastuzumab; Everolimus 10 mg daily in combination with paclitaxel 80mg/m2 weekly on days 1, 8, 15 and trastuzumab 2mg/kg weekly on days 1, 8, 15, 22	Drug: Everolimus; Everolimus was administered in a continuous oral daily dosing of 10 mg (two 5-mg tablets).; Other Names: RAD001; Drug: Trastuzumab; Trastuzumab, 2 mg/kg weekly was used intravenously.; Drug: Paclitaxel; Paclitaxel, 80 mg/m2 weekly was used intravenously.
Placebo Comparator: Placebo + Paclitaxel + Trastuzumab; Placebo of everolimus 10 mg daily in combination with paclitaxel 80mg/m2 weekly on days 1, 8, 15 and trastuzumab 2mg/kg weekly on days 1, 8, 15, 22	Drug: Trastuzumab; Trastuzumab, 2 mg/kg weekly was used intravenously.; Drug: Paclitaxel; Paclitaxel, 80 mg/m2 weekly was used intravenously.; Drug: Placebo; Everolimus placebo was administered in a continuous oral daily dosing of 10 mg (two 5-mg tablets).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) Per Investigators' Assessment Based on Local Radiology Review - Full Population	PFS is defined as the time from the date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first. This was assessed in the full patient population.	date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first, reported between day of first patient randomized up to about 56 months
Progression-free Survival (PFS) Per Investigators' Assessment Based on Local Radiology Review - (Hormone Receptor (HR)-Negative Population	PFS is defined as the time from the date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first. This was assessed in the HR-negative patient population.	date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first, reported between day of first patient randomized up to about 56 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) - Full Population	OS is defined as the time from date of randomization to the date of death due to any cause. For patients with documented progression, survival follow up was performed either by telephone or clinic visit at least every 3 months. Additional survival updates were requested prior to interim or final analysis or prior to providing data to the health authorities. This was assessed in the full patient population.	up to about 76 months
Overall Survival (OS) - HR-negative Population	OS is defined as the time from date of randomization to the date of death due to any cause. For patients with documented progression, survival follow up was performed either by telephone or clinic visit at least every 3 months. Additional survival updates were requested prior to interim or final analysis or prior to providing data to the health authorities. This was assessed in the HR-negative patient population.	up to about 76 months
Overall Response Rate (ORR) - Full Population	ORR is defined as the percentage of participants whose best overall response is either complete response (CR) or partial response (PR) according to RECIST. This was assessed in the full patient population. Complete response is achieved when all lesions evaluated at Baseline are absent at subsequent visit.	up to about 23 months
Overall Response Rate (ORR) - HR-negative Population	ORR is defined as the percentage of participants whose best overall response is either complete response (CR) or partial response (PR) according to RECIST. This was assessed in a subset of patients with Hormone Receptor Negative disease. Complete response is achieved when all lesions evaluated at Baseline are absent at subsequent visit.	up to about 23 months
Clinical Benefit Rate (CBR) Equal to or Greater Than 24 Weeks - Full Population	CBR is defined as the percentage of participants whose best overall response is either complete response (CR), a partial response (PR) or stable disease (SD) lasting for at least 24 weeks, according to RECIST. This was assessed in the full patient population. Complete response is achieved when all lesions evaluated at Baseline are absent at subsequent visit.	up to about 23 months
Clinical Benefit Rate (CBR) Equal to or Greater Than 24 Weeks - HR-negative Population	CBR is defined as the percentage of participants whose best overall response is either complete response (CR), a partial response (PR) or stable disease (SD) lasting for at least 24 weeks, according to RECIST. This was assessed in a subset of patients with Hormone Receptor Negative disease. Complete response is achieved when all lesions evaluated at Baseline are absent at subsequent visit.	up to about 23 months
Time to Overall Response Based on Investigator - Full Population	Time to overall response defined as the time between date of randomization until first documented response Complete reseponse (CR) or partial response (PR) ), according to RECIST. This was assessed in the full patient population and in a subset of patients with Hormone Receptor Negative disease. Complete response is achieved when all lesions evaluated at Baseline are absent at subsequent visit.	up to about 23 months
Time to Overall Response Based on Investigator - HR-negative Population	Time to overall response defined as the time between date of randomization until first documented response Complete reseponse (CR) or partial response (PR) ), according to RECIST. This was assessed in the full patient population and in a subset of patients with Hormone Receptor Negative disease. Complete response is achieved when all lesions evaluated at Baseline are absent at subsequent visit.	up to about 23 months
Overall Response (OR) - Full Population	OR applies only to patients whose best OR was CR or PR. Start date = date of first documented response (CR or PR) and end date = date of documented response (CR or PR) and end date = date of event defined as the first documented progression or death due to underlying cause. Complete response is achieved when all lesions evaluated at Baseline are absent at subsequent visit.	up to about 23 months
Overall Response (OR) - HR-negative Population	OR applies only to patients whose best OR was CR or PR. Start date = date of first documented response (CR or PR) and end date = date of documented response (CR or PR) and end date = date of event defined as the first documented progression or death due to underlying cause. This was assessed in the HR-negative patient population. Complete response is achieved when all lesions evaluated at Baseline are absent at subsequent visit.	up to about 23 months
Everolimus Blood Level Concentrations at Steady States for Everolimus	Blood levels at steady states for everolimus 10 mg/day and 5 mg/day. Only valid samples are included. Some patients had dose reduction to 5 mg daily dose therefore the everolimus blood concentration for them have been summarized separately. Cycle = 28 days	predose, 2 hours post-dose at Cycle 2/Day 1, Cycle 2/Day 15, Cycle 2/ Day 22
Paclitaxel Plasma Concentrations	Blood levels at steady states for everolimus/placebo	Cycle 2/Day 15 (Pre-infusion and end of infusion)
Trastuzumab Serum Concentrations	Blood levels at steady states for everolimus/placebo	Cycle 4/Day 1 (Pre-infusion and end of infusion)
Time to Deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG-PS) Score - Full Population	Time to definitive deterioration of the ECOG PS by one category of the score from baseline will be performed. Baseline is the last available assessment on or before randomization date. A deterioration is considered definitive if no improvements in the ECOG PS status is observed at a subsequent time of measurement during the treatment period following the time point where the deterioration is observed.	up to about 56 months
Time to Deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG-PS) Score - HR-negative Population	Time to definitive deterioration of the ECOG PS by one category of the score from baseline will be performed. Baseline is the last available assessment on or before randomization date. A deterioration is considered definitive if no improvements in the ECOG PS status is observed at a subsequent time of measurement during the treatment period following the time point where the deterioration is observed.	up to about 56 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Toi M, Shao Z, Hurvitz S, Tseng LM, Zhang Q, Shen K, Liu D, Feng J, Xu B, Wang X, Lee KS, Ng TY, Ridolfi A, Noel-Baron F, Ringeisen F, Jiang Z. Efficacy and safety of everolimus in combination with trastuzumab and paclitaxel in Asian patients with HER2+ advanced breast cancer in BOLERO-1. Breast Cancer Res. 2017 Apr 11;19(1):47. doi: 10.1186/s13058-017-0839-0.
• Buyse M, Hurvitz SA, Andre F, Jiang Z, Burris HA, Toi M, Eiermann W, Lindsay MA, Slamon D. Statistical controversies in clinical research: statistical significance-too much of a good thing .... Ann Oncol. 2016 May;27(5):760-2. doi: 10.1093/annonc/mdw047. Epub 2016 Feb 9.
• Hurvitz SA, Andre F, Jiang Z, Shao Z, Mano MS, Neciosup SP, Tseng LM, Zhang Q, Shen K, Liu D, Dreosti LM, Burris HA, Toi M, Buyse ME, Cabaribere D, Lindsay MA, Rao S, Pacaud LB, Taran T, Slamon D. Combination of everolimus with trastuzumab plus paclitaxel as first-line treatment for patients with HER2-positive advanced breast cancer (BOLERO-1): a phase 3, randomised, double-blind, multicentre trial. Lancet Oncol. 2015 Jul;16(7):816-29. doi: 10.1016/S1470-2045(15)00051-0. Epub 2015 Jun 16.

Helpful Links

• Visit 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 (Actual): September 10, 2009
• Primary Completion (Actual): May 30, 2014
• Study Completion (Actual): October 23, 2017

Study Registration Dates

• First Submitted: April 2, 2009
• First Submitted That Met QC Criteria: April 3, 2009
• First Posted (Estimate): April 6, 2009

Study Record Updates

• Last Update Posted (Actual): December 19, 2018
• Last Update Submitted That Met QC Criteria: December 18, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: Breast Cancer; first line; HER2 Positive; everolimus; metastatic; Metastatic Breast Cancer; Trastuzumab; Paclitaxel; mTOR; HER2+; RAD001; locally advanced; First Line Therapy
• 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; Paclitaxel; Trastuzumab; Everolimus
• Other Study ID Numbers: CRAD001J2301; 2008-006556-21 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No