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AzTrials

Breast CancerPhase 3BOLERO-2NCT00863655

Everolimus in Combination With Exemestane in the Treatment of Postmenopausal Women With Estrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer Who Are Refractory to Letrozole or Anastrozole

A Phase 3 study testing Everolimus and Exemestane in people with Breast Cancer, run by Novartis Pharmaceuticals at 200 sites in 24 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

There are no treatments specifically approved after recurrence or progression on a non steroidal aromatase inhibitors (NSAI). In light of the need for new treatment options for postmenopausal women after failure of prior NSAI therapy, the purpose of this Phase III study is to compare efficacy and safety of a treatment… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
Everolimus and Exemestane
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
724 participants
Where
200 sitesin 24 countries
Study dates
3 Jun 2009to 4 Dec 2014
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adult women (≥ 18 years of age) with metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy.
  • Histological or cytological confirmation of estrogen-receptor positive (ER+) breast cancer
  • Postmenopausal women.
  • Disease refractory to non steroidal aromatase inhibitors (NSAI),
  • Radiological or clinical evidence of recurrence or progression on or after the last systemic therapy prior to randomization.
  • Patients must have at least one lesion that can be accurately measured or bone lesions in the absence of measurable disease as defined above.

Who cannot join

  • HER2-overexpressing patients
  • Patients with only non-measurable lesions other than bone metastasis (e.g. pleural effusion, ascites etc.).
  • Patients who received more than one chemotherapy line for Advanced Breast Cancer.
  • Previous treatment with exemestane or mTOR inhibitors.
  • Known hypersensitivity to mTOR inhibitors, e.g. sirolimus (rapamycin).
  • Radiotherapy within four weeks prior to randomization
  • Currently receiving hormone replacement therapy,
  • Other protocol-defined inclusion/exclusion criteria may apply

Trial locations and contacts

200 sites in 24 countries.

200 sites in 24 countries

United States63 sites

  • University of New Mexico Cancer Research Center Dept of UNM Cancer & Research

    Albuquerque, New Mexico, 87131

  • Kaiser Permanente Medical Group Kaiser Permanente-Moanalua M.C

    Anaheim, California, 92807

  • Anne Arundel Health System Research Institute Wayson Pavilion

    Annapolis, Maryland, 21401

  • Comprehensive Blood and Cancer Center Dept. of CBCC (3)

    Bakersfield, California, 93309

  • Mercy Medical Center Medical Oncology & Hematology

    Baltimore, Maryland, 21202

  • Weinberg Cancer Institute at Franklin Square Hospital

    Baltimore, Maryland, 21237-3998

  • Maryland Hematology/Oncology Associates, P.A.

    Baltimore, Maryland, 21237

  • Hematology Oncology Clinic Hematology Oncology Clinic (2)

    Baton Rouge, Louisiana, 70808

  • Comprehensive Cancer Center - Boca Raton Deerfield Beach

    Boca Raton, Florida, 33248

  • Lahey Clinic Dept of Lahey Clinic (2)

    Burlington, Massachusetts, 01805

  • Ironwood Cancer and Research Centers

    Chandler, Arizona, 85224

  • Medical University of South Carolina -Hollings Cancer Center Dept. MUSC/HollingsCancerCtr

    Charleston, South Carolina, 29425

  • Regional Cancer Care Associates Dept. of the CCHD

    Cherry Hill, New Jersey, 08003

  • Rush University Medical Center Study Coordinator

    Chicago, Illinois, 60612

  • University of Texas Southwestern Medical Center SimmonsComprehensiveCancerCtr.

    Dallas, Texas, 75390-8852

  • Florida Cancer Research Institute

    Davie, Florida, 33328

  • Georgia Cancer Specialists. Drug Ship

    Decatur, Georgia, 30033

  • Fairview Southdale Medical Oncology Clinic

    Edina, Minnesota, 55435

  • Trinitas Comprehensive Cancer Center Dept. of Trinitas

    Elizabeth, New Jersey, 07207

  • Highlands Oncology Group DeptofHighlandsOncologyGrp(2)

    Fayetteville, Arkansas, 72703

  • Florida Cancer Specialists DeptofFloridaCancerSpecialists

    Fort Myers, Florida, 33901

  • The Center for Cancer and Blood Disorders Dept. of The Ctr for C & BD(2)

    Fort Worth, Texas, 76104

  • Frederick Memorial Hospital Dept. of FMH-IRB

    Frederick, Maryland, 21701

  • Cancer Care Associates Dept.ofCancerCareAssoc. (2)

    Fresno, California, 93720

  • Grass Valley Hematology Oncology Medical Group Dept. of Grass Valley Hem/Onc

    Grass Valley, California, 95945

  • Penn State University / Milton S. Hershey Medical Center Division of Oncology (2)

    Hershey, Pennsylvania, 17033-0850

  • Memorial Hospital Memorial Cancer Institute

    Hollywood, Florida, 33021

  • University of Texas/MD Anderson Cancer Center Dept.ofMDAndersonCancerCtr(2)

    Houston, Texas, 77030-4009

  • Hematology Oncology of Indiana

    Indianapolis, Indiana, 46260

  • Scripps Clinic SC

    La Jolla, California, 92121

  • Horizon Oncology Center

    Lafayette, Indiana, 47905

  • Clinical Research Alliance Dept.ofArenaOncologyAssoc(2)

    Lake Success, New York, 11042

  • ProHealth Care

    Lake Success, New York, 11042

  • Cancer Centers of Southwest Oklahoma Cancer Research Dept.of Southwest Oklahoma

    Lawton, Oklahoma, 73505

  • Southeast Nebraska Oncology Cancer Center

    Lincoln, Nebraska, 68510

  • The Angeles Clinic and Research Institute

    Los Angeles, California, 90025

  • USC/Kenneth Norris Comprehensive Cancer Center Regulatory Contact 3

    Los Angeles, California, 90053

  • University of Louisville / James Graham Brown Cancer Center SC

    Louisville, Kentucky, 40202

  • University of Wisconsin Hospital & Clinics UW ComprehensiveCancerCtr(2)

    Madison, Wisconsin, 53792

  • Crescent City Research Consortium, LLC Dept of Hem&Onc Specialist - 2

    Metairie, Louisiana, 70006

  • Sarah Cannon Research Institute Dept.ofSarahCannonCancerCtr(5)

    Nashville, Tennessee, 37203

  • Beth Israel Medical Center Dept.ofBeth Israel Med. Ctr(2)

    New York, New York, 10003

  • Weill Cornell Medical College Weill Cornell Med. Ctr.

    New York, New York, 10021

  • Hematology Oncology Association of Rockland

    Nyack, New York, 10960

  • Northern Utah Cancer Associates SC

    Ogden, Utah, 84403-3105

  • MD Anderson Cancer Center - Orlando Dept.ofMDACC-Orlando(2)

    Orlando, Florida, 32806

  • Oncology Specialists, SC Dept.of Oncology Specialists

    Park Ridge, Illinois, 60068-0736

  • Central Utah Clinic CRAD001Y2301

    Provo, Utah, 84604

  • Medical Oncology & Hematology Associates of Northern VA Med. Onc&Hem Assoc. of No.VA

    Reston, Virginia, 20190

  • Hope Oncology HOPE Richardson

    Richardson, Texas, 75080

  • Utah Cancer Specialists Dept.of Utah Cancer Spec. (2)

    Salt Lake City, Utah, 84106

  • University of Utah / Huntsman Cancer Institute Dept.ofHuntsmanCancerInst.(2)

    Salt Lake City, Utah, 84112

  • Sharp Memorial Hospital SharpClinicalOncologyResearch

    San Diego, California, 92123

  • University of California San Francisco UCSF Medical Center

    San Francisco, California, 94101

  • Premiere Oncology/Pinnacle Oncology Hematology Dept.ofPremiereOncologyAZ

    Santa Monica, California, 90404

  • St Joseph Heritage Healthcare Dept. of RRMG (4)

    Santa Rosa, California, 94503

  • Holy Cross Hospital Holy Cross

    Silver Spring, Maryland, 20910

  • St. Louis Cancer & Breast Institute Dept.ofSt.LouisCancer&Breast

    St Louis, Missouri, 63141

  • Cancer Care Associates SC

    Tulsa, Oklahoma, 74136

  • Marion L. Shepard Cancer Center

    Washington, North Carolina, 27889

  • Palm Beach Cancer Institute

    West Palm Beach, Florida, 33401

  • Cancer Center of Kansas Dept.ofCancerCtr.ofKansas

    Wichita, Kansas, 67214-3728

  • Florida Medical Clinic PA Dept.ofFloridaMedicalClinic

    Zephyrhills, Florida, 33542

Other trials in United States

Japan20 sites

  • Novartis Investigative Site

    Bunkyo-ku, Tokyo, 113-8677

  • Novartis Investigative Site

    Chuo-ku, Tokyo, 104-0045

  • Novartis Investigative Site

    Chuo-ku, Tokyo, 104-8560

  • Novartis Investigative Site

    Fukuoka, Fukuoka, 811-1395

  • Novartis Investigative Site

    Hidaka, Saitama, 350-1298

  • Novartis Investigative Site

    Isehara, Kanagawa, 259-1193

  • Novartis Investigative Site

    Kagoshima, Kagoshima-ken, 892-0833

  • Novartis Investigative Site

    Kashiwa, Chiba, 277-8577

  • Novartis Investigative Site

    Kitaadachi-gun, Saitama, 362-0806

  • Novartis Investigative Site

    Kitakyushu, Fukuoka, 802-0077

  • Novartis Investigative Site

    Koto, Tokyo, 135-8550

  • Novartis Investigative Site

    Kumamoto, Kumamoto, 860-8556

  • Novartis Investigative Site

    Kyoto, Kyoto, 606-8507

  • Novartis Investigative Site

    Maebashi, Gunma, 371-8511

  • Novartis Investigative Site

    Matsuyama, Ehime, 791-0280

  • Novartis Investigative Site

    Nagoya, Aichi-ken, 464-8681

  • Novartis Investigative Site

    Osaka, Osaka, 537-8511

  • Novartis Investigative Site

    Osaka, Osaka, 540-0006

  • Novartis Investigative Site

    Sapporo, Hokkaido, 060-8648

  • Novartis Investigative Site

    Suita, Osaka, 565-0871

Other trials in Japan

Canada16 sites

  • Novartis Investigative Site

    Calgary, Alberta, T2N 4N2

  • Novartis Investigative Site

    Cambridge, Ontario, N1R 3G2

  • Novartis Investigative Site

    Greenfield Park, Quebec, J4V 2H1

  • Novartis Investigative Site

    Halifax, Nova Scotia, B3H 2Y9

  • Novartis Investigative Site

    London, Ontario, N6A 4L6

  • Novartis Investigative Site

    Moncton, New Brunswick, E1C 6Z8

  • Novartis Investigative Site

    Montreal, Quebec, H2W 1S6

  • Novartis Investigative Site

    Montreal, Quebec, H2W 1T8

  • Novartis Investigative Site

    Montreal, Quebec, H4J 1C5

  • Novartis Investigative Site

    Newmarket, Ontario, J7Y 2P9

  • Novartis Investigative Site

    Québec, Quebec, G1S 4L8

  • Novartis Investigative Site

    Sherbrooke, Quebec, J1H 5N4

  • Novartis Investigative Site

    St. Catharines, Ontario, L2S 0A9

  • Novartis Investigative Site

    Toronto, Ontario, M4C 3E7

  • Novartis Investigative Site

    Toronto, Ontario, M4N 3M5

  • Novartis Investigative Site

    Weston, Ontario, M9N 1N8

Other trials in Canada

Spain12 sites

  • Novartis Investigative Site

    A Coruña, Galicia, 15006

  • Novartis Investigative Site

    Barcelona, Catalonia, 08035

  • Novartis Investigative Site

    Lleida, Catalonia, 25198

  • Novartis Investigative Site

    Madrid, Madrid, 28033

  • Novartis Investigative Site

    Madrid, Madrid, 28041

  • Novartis Investigative Site

    Madrid, Madrid, 28046

  • Novartis Investigative Site

    Málaga, Andalusia, 29010

  • Novartis Investigative Site

    Mallorca, Balearic Islands, 07198

  • Novartis Investigative Site

    Palma de Mallorca, Balearic Islands, 07120

  • Novartis Investigative Site

    Santiago de Compostela, Galicia, 15706

  • Novartis Investigative Site

    Seville, Andalusia, 41017

  • Novartis Investigative Site

    Terrassa, Catalonia, 08221

Other trials in Spain

Italy10 sites

  • Novartis Investigative Site

    Antella - Bagno A Ripoli, FI, 50011

  • Novartis Investigative Site

    Brindisi, BR, 72100

  • Novartis Investigative Site

    Catania, CT, 95100

  • Novartis Investigative Site

    Genova, GE, 16132

  • Novartis Investigative Site

    Perugia, PG, 06129

  • Novartis Investigative Site

    Province of Macerata, MC, 62100

  • Novartis Investigative Site

    Saronno, Va, 21047

  • Novartis Investigative Site

    Terni, TR, 05100

  • Novartis Investigative Site

    Torino, TO, 10126

  • Novartis Investigative Site

    Varese, VA, 21100

Other trials in Italy

France9 sites

  • Novartis Investigative Site

    La Roche-sur-Yon, 85925

  • Novartis Investigative Site

    Le Mans, 72000

  • Novartis Investigative Site

    Lyon, 69373

  • Novartis Investigative Site

    Marseille, 13008

  • Novartis Investigative Site

    Paris, 75010

  • Novartis Investigative Site

    Rouen, 76000

  • Novartis Investigative Site

    Rouen, 76038

  • Novartis Investigative Site

    Saint-Herblain Cédex, 44805

  • Novartis Investigative Site

    Saint-Nazaire, 44600

Other trials in France

Germany8 sites

  • Novartis Investigative Site

    Berlin, 10098

  • Novartis Investigative Site

    Düsseldorf, 40225

  • Novartis Investigative Site

    Frankfurt, 60389

  • Novartis Investigative Site

    Mannheim, 68165

  • Novartis Investigative Site

    München, 80637

  • Novartis Investigative Site

    München, 81377

  • Novartis Investigative Site

    Münster, 48149

  • Novartis Investigative Site

    Trier, 54290

Other trials in Germany

Australia6 sites

  • Novartis Investigative Site

    Bedford Park, South Australia, 5042

  • Novartis Investigative Site

    Nambour, Queensland, 4560

  • Novartis Investigative Site

    Parkville, Victoria, 3002

  • Novartis Investigative Site

    Parkville, Victoria, 3050

  • Novartis Investigative Site

    Redcliffe, Queensland, 4020

  • Novartis Investigative Site

    Subiaco, Western Australia, 6008

Other trials in Australia

Belgium6 sites

  • Novartis Investigative Site

    Brussels, 1000

  • Novartis Investigative Site

    Brussels, 1090

  • Novartis Investigative Site

    Leuven, 3000

  • Novartis Investigative Site

    Liège, 4000

  • Novartis Investigative Site

    Sint-Niklaas, 9100

  • Novartis Investigative Site

    Wilrijk, 2610

Other trials in Belgium

Netherlands6 sites

  • Novartis Investigative Site

    Alkmaar, 1815 JD

  • Novartis Investigative Site

    Amsterdam, 1090 HM

  • Novartis Investigative Site

    Dordrecht, 3318AT

  • Novartis Investigative Site

    Eindhoven, Netherlands, 5631 BM

  • Novartis Investigative Site

    Sittard-Geleen, 6162 BG

  • Novartis Investigative Site

    The Hague, 2545 CH

Other trials in Netherlands

United Kingdom6 sites

  • Novartis Investigative Site

    Broomfield, Chelmsford, CM1 7ET

  • Novartis Investigative Site

    Cardiff, CF14 2TL

  • Novartis Investigative Site

    Nottingham, NG5 1PB

  • Novartis Investigative Site

    Sheffield, S10 2SJ

  • Novartis Investigative Site

    Southampton, SO16 6YD

  • Novartis Investigative Site

    Truro, Cornwall, TR1 3LJ

Other trials in United Kingdom

Austria5 sites

  • Novartis Investigative Site

    Innsbruck, Austria, A-6020

  • Novartis Investigative Site

    Linz, A-4010

  • Novartis Investigative Site

    Salzburg, 5020

  • Novartis Investigative Site

    Vienna, A-1090

  • Novartis Investigative Site

    Wels, Austria, A-4600

Other trials in Austria

Brazil5 sites

  • Novartis Investigative Site

    Porto Alegre, Rio Grande do Sul, 90560-030

  • Novartis Investigative Site

    Rio de Janeiro, Rio de Janeiro, 20230-130

  • Novartis Investigative Site

    Salvador, Estado de Bahia, 41825-010

  • Novartis Investigative Site

    São Paulo, São Paulo, 01246-000

  • Novartis Investigative Site

    Uberlândia, Minas Gerais, 38408-150

Other trials in Brazil

Thailand4 sites

  • Novartis Investigative Site

    Bangkok, 10400

  • Novartis Investigative Site

    Bangkok, 10700

  • Novartis Investigative Site

    Chiang Mai, 50200

  • Novartis Investigative Site

    Songkhla, 90110

Other trials in Thailand

Czechia3 sites

  • Novartis Investigative Site

    Brno, Czech Republic, 656 53

  • Novartis Investigative Site

    Olomouc, CZE, 775 20

  • Novartis Investigative Site

    Prague, Czech Republic, 14044

Other trials in Czechia

Egypt3 sites

  • Novartis Investigative Site

    Alexandria

  • Novartis Investigative Site

    Cairo

  • Novartis Investigative Site

    Menoufiya, Egypt

Other trials in Egypt

Hungary3 sites

  • Novartis Investigative Site

    Budapest, H-1122

  • Novartis Investigative Site

    Szeged, H-6720

  • Novartis Investigative Site

    Szolnok, H-5000

Other trials in Hungary

Poland3 sites

  • Novartis Investigative Site

    Krakow, 31-108

  • Novartis Investigative Site

    Rzeszów, 35-021

  • Novartis Investigative Site

    Warsaw, 04-125

Other trials in Poland

South Korea3 sites

  • Novartis Investigative Site

    Hwasun-gun, Jeollanam-do, 58128

  • Novartis Investigative Site

    Seoul, Korea, 03722

  • Novartis Investigative Site

    Seoul, 01812

Other trials in South Korea

Sweden3 sites

  • Novartis Investigative Site

    Stockholm, SE-118 83

  • Novartis Investigative Site

    Stockholm, SE-171 76

  • Novartis Investigative Site

    Uppsala, SE-751 85

Other trials in Sweden

Turkey (Türkiye)3 sites

  • Novartis Investigative Site

    Altunizade, 34662

  • Novartis Investigative Site

    Ankara, 06100

  • Novartis Investigative Site

    Izmir, Turkey, 35040

Other trials in Turkey (Türkiye)

Hong Kong1 site

  • Novartis Investigative Site

    Hong Kong SAR

Other trials in Hong Kong

New Zealand1 site

  • Novartis Investigative Site

    Christchurch, Christchurch, 8001

Other trials in New Zealand

Norway1 site

  • Novartis Investigative Site

    Lørenskog, NO-1478

Other trials in Norway

About this study

Official title: A Randomized Double-Blind, Placebo-Controlled Study of Everolimus in Combination With Exemestane in the Treatment of Postmenopausal Women With Estrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer Who Are Refractory to Letrozole or Anastrozole

There are no treatments specifically approved after recurrence or progression on a non steroidal aromatase inhibitors (NSAI). In light of the need for new treatment options for postmenopausal women after failure of prior NSAI therapy, the purpose of this Phase III study is to compare efficacy and safety of a treatment with exemestane + everolimus to exemestane + placebo in postmenopausal women with estrogen receptor positive locally advanced or metastatic breast cancer refractory to NSAI.

Conditions
Breast Cancer
Being tested
Everolimus, Exemestane, Everolimus Placebo
Keywords
Breast Cancer, Estrogen Receptor positive, ER+, exemestane, mTOR, everolimus, refractory, NSAI
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EverolimusDrug

    Also called RAD001

    Everolimus was formulated as tablets of 5-mg strength and was packaged into blister packs . Everolimus (two 5 mg tablets daily) were administered in a blinded manner on their respective treatment arms by continuous oral daily dosing.

  • ExemestaneDrug

    Exemestane 25 mg orally daily.

  • Everolimus PlaceboDrug

    Placebo was formulated to be indistinguishable from the everolimus tablets. Matching placebo (two tablets daily) were administered in a blinded manner on their respective treatment arms by continuous oral daily dosing.

Study groups in NCT00863655
Study groupRoleWhat they receive
Everolimus + ExemestaneExperimentalEverolimus 10 mg daily in combination with exemestane 25 mg daily
Receives: Drug: Everolimus; Drug: Exemestane
Placebo + ExemestaneActive comparatorPlacebo of everolimus in combination with exemestane 25 mg daily
Receives: Drug: Exemestane; Drug: Everolimus Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free Survival (PFS) Based on Local Radiology Review of Tumor Assessments.

    Progression-free survival, the primary endpoint in this study, is defined as the time from the date of randomization to the date of first documented radiological progression or death due to any cause. Disease progression was based on the tumor assessment by the local radiologist or investigator using RECIST 1.0 criteria. If a patient did not progress or known to have died at the date of the analysis cut-off or start of another antineoplastic therapy, the PFS date was censored to the date of last adequate tumor assessment prior to cut-off date or start of antineoplastic therapy. For patients with lytic or mixed (lytic+sclerotic) bone lesions, the following is considered progression: appearance of ≥1 new lytic lesions in bone; the appearance of ≥ new lesions outside of bone and unequivocal progression of existing bone lesions.

    Measured: 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 19 months

Secondary outcomes (11)

  1. Overall Survival (OS) by Number of Deaths

    Overall survival, the key secondary endpoint in this study, is defined as the time from date of randomization to the date of death due to any cause. If a patient is not known to have died, survival was censored at the date of last contact.

    Measured: up to 53 months

  2. Overall Survival (OS) by Median

    Overall survival, the key secondary endpoint in this study, is defined as the time from date of randomization to the date of death due to any cause.

    Measured: up to 53 months

  3. Overall Response Rate (ORR)

    Overall response rate (ORR) is the percentage of patients with a best overall response of complete response (CR) or partial response (PR) according to RECIST 1.0. Per RECIST criteria 1.0, CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters.

    Measured: up to 21 months

  4. Clinical Benefit Rate (CBR)

    CBR is defined as the percentage of patients with best overall response of either complete response (CR), a partial response (PR) or stable disease (SD) >= 24 weeks, according to RECIST 1.0. Per RECIST criteria 1.0, CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters; 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.

    Measured: up to 21 months

  5. Proportion of Patients With no Deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG PS) Using Kaplan-Meier

    The ECOG PS (Eastern Cooperative Oncology Group Performance Scale) is a standard criteria for measuring how treatment of cancer impacts level of functioning in terms of the ability to care for oneself, daily activity, \& physical ability (walking, working, etc.). Scale score ranges:0 to 5, 5 being the worst. 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. 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. A deterioration of ECOG is an increase of 1 of the ECOG PS without improvement back to initial level at a subsequent time of measurement.

    Measured: 2, 4, 6, 9 months

  6. Patient-reported Outcomes (PROs): Time to Deterioration of PRO Scores Using Kaplan Meier - EORTC QLQ-C30

    The QLQ-C30 is composed of both multi-item scales and single-item measures. These include 5 functional scales, 3 symptom scales, a global health status - QoL scale, and 6 single items. Each of the multi-item scales includes a different set of items - no item occurs in more than 1 scale. All of the scales measures range in score from 0 to 100. A high scale score = higher response level. Thus a high score for a functional scale represents a healthy level of function, a high score for the global health status / QoL represents a high quality of life but a high score for a symptom scale / item represents a high level of symptomatology / problems. The principle for scoring these scales: 1.) Estimate the average of the items that contribute to the scale = raw score. 2.) Linear transformation to standardize the raw score, so that scores range from 0 to 100; a higher score represents a higher ("better") level of functioning, or a higher ("worse") level of symptoms.

    Measured: Up to 21 months

  7. Proportion of Patients With Having no Overall Response Based on Investigator Assessment

    overall response = complete response (CR) + partial response (PR) per RECIST 1.0 Time to overall response (CR or PR) based on investigator is the time between date of randomization/start of treatment until first documented response (CR or PR). This analysis included all patients/responders. Patients who did not achieve a confirmed PR or CR were censored at last adequate tumor assessment date when they did not progress. Per RECIST criteria 1.0, CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters.

    Measured: 2, 4, 6, 9 months

  8. Duration of Response (Among Participants With Best Overall Response of CR or PR) Estimated Per Kaplan-Meier

    Duration of response of CR or PR based on investigator applies only to patients whose best overall response was CR or PR (RECIST 1.0). The start date was the date of first documented response (CR or PR) and the end date and censoring is defined the same as that for time to progression. Per RECIST criteria 1.0, CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters.

    Measured: 21 months

  9. Everolimus Concentrations at Week 4

    Characterize the pharmacokinetics (PK) of everolimus in combination with exemestane using Cmin (pre-dose) and C2h (post-dose) at week 4 in a small group of patients.

    Measured: pre-dose, 2 hours post-dose

  10. Exemestane Concentrations at Week 4

    Characterize the PK of exemestane in combination with or without everolimus using Cmin and C2h at week 4 in a small group of patients.

    Measured: predose, 2 hours post-dose

  11. Estradiol Plasma Concentrations

    Compare estradiol concentrations from baseline to week 4 in both treatment arms.

    Measured: Baseline, Week 4

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Mar 2009 (estimated)
  2. Study start3 Jun 2009
  3. Primary completion4 Dec 2014
  4. Study completion4 Dec 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
724 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00863655
Sponsor's protocol ID
CRAD001Y2301
Other IDs
2008-008698-69, 2008
Acronym
BOLERO-2
Status last verified
Mar 2017
First submitted
16 Mar 2009
Last updated
2 May 2017
Data monitoring committee
Yes

Publications

  • Luftner D, Schuetz F, Schneeweiss A, Hartkopf A, Bloch W, Decker T, Uleer C, Stotzer O, Foerster F, Schmidt M, Mundhenke C, Tesch H, Jackisch C, Fischer T, Kreuzeder J, Guderian G, Fasching PA. Efficacy and safety of everolimus plus exemestane in patients with hormone receptor-positive, HER-2-negative advanced breast cancer: Results from the open-label, multicentre, non-interventional BRAWO study. Int J Cancer. 2024 Jul 1;155(1):128-138. doi: 10.1002/ijc.34912. Epub 2024 Mar 6.

    PubMed 38447007

  • Wedam SB, Beaver JA, Amiri-Kordestani L, Bloomquist E, Tang S, Goldberg KB, Sridhara R, Ibrahim A, Kim G, Kluetz P, McKee A, Pazdur R. US Food and Drug Administration Pooled Analysis to Assess the Impact of Bone-Only Metastatic Breast Cancer on Clinical Trial Outcomes and Radiographic Assessments. J Clin Oncol. 2018 Apr 20;36(12):1225-1231. doi: 10.1200/JCO.2017.74.6917. Epub 2018 Mar 9.

    PubMed 29522361

  • Chandarlapaty S, Chen D, He W, Sung P, Samoila A, You D, Bhatt T, Patel P, Voi M, Gnant M, Hortobagyi G, Baselga J, Moynahan ME. Prevalence of ESR1 Mutations in Cell-Free DNA and Outcomes in Metastatic Breast Cancer: A Secondary Analysis of the BOLERO-2 Clinical Trial. JAMA Oncol. 2016 Oct 1;2(10):1310-1315. doi: 10.1001/jamaoncol.2016.1279.

    PubMed 27532364

  • Hortobagyi GN, Chen D, Piccart M, Rugo HS, Burris HA 3rd, Pritchard KI, Campone M, Noguchi S, Perez AT, Deleu I, Shtivelband M, Masuda N, Dakhil S, Anderson I, Robinson DM, He W, Garg A, McDonald ER 3rd, Bitter H, Huang A, Taran T, Bachelot T, Lebrun F, Lebwohl D, Baselga J. Correlative Analysis of Genetic Alterations and Everolimus Benefit in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From BOLERO-2. J Clin Oncol. 2016 Feb 10;34(5):419-26. doi: 10.1200/JCO.2014.60.1971. Epub 2015 Oct 26.

    PubMed 26503204

  • Piccart M, Hortobagyi GN, Campone M, Pritchard KI, Lebrun F, Ito Y, Noguchi S, Perez A, Rugo HS, Deleu I, Burris HA 3rd, Provencher L, Neven P, Gnant M, Shtivelband M, Wu C, Fan J, Feng W, Taran T, Baselga J. Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2dagger. Ann Oncol. 2014 Dec;25(12):2357-2362. doi: 10.1093/annonc/mdu456. Epub 2014 Sep 17.

    PubMed 25231953

  • Rugo HS, Pritchard KI, Gnant M, Noguchi S, Piccart M, Hortobagyi G, Baselga J, Perez A, Geberth M, Csoszi T, Chouinard E, Srimuninnimit V, Puttawibul P, Eakle J, Feng W, Bauly H, El-Hashimy M, Taran T, Burris HA 3rd. Incidence and time course of everolimus-related adverse events in postmenopausal women with hormone receptor-positive advanced breast cancer: insights from BOLERO-2. Ann Oncol. 2014 Apr;25(4):808-815. doi: 10.1093/annonc/mdu009. Epub 2014 Mar 10.

    PubMed 24615500

  • Yardley DA, Noguchi S, Pritchard KI, Burris HA 3rd, Baselga J, Gnant M, Hortobagyi GN, Campone M, Pistilli B, Piccart M, Melichar B, Petrakova K, Arena FP, Erdkamp F, Harb WA, Feng W, Cahana A, Taran T, Lebwohl D, Rugo HS. Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis. Adv Ther. 2013 Oct;30(10):870-84. doi: 10.1007/s12325-013-0060-1. Epub 2013 Oct 25.

    PubMed 24158787

  • Campone M, Beck JT, Gnant M, Neven P, Pritchard KI, Bachelot T, Provencher L, Rugo HS, Piccart M, Hortobagyi GN, Nunzi M, Heng DY, Baselga J, Komorowski A, Noguchi S, Horiguchi J, Bennett L, Ziemiecki R, Zhang J, Cahana A, Taran T, Sahmoud T, Burris HA 3rd. Health-related quality of life and disease symptoms in postmenopausal women with HR(+), HER2(-) advanced breast cancer treated with everolimus plus exemestane versus exemestane monotherapy. Curr Med Res Opin. 2013 Nov;29(11):1463-73. doi: 10.1185/03007995.2013.836078. Epub 2013 Sep 4.

    PubMed 23962028

  • Noguchi S, Masuda N, Iwata H, Mukai H, Horiguchi J, Puttawibul P, Srimuninnimit V, Tokuda Y, Kuroi K, Iwase H, Inaji H, Ohsumi S, Noh WC, Nakayama T, Ohno S, Rai Y, Park BW, Panneerselvam A, El-Hashimy M, Taran T, Sahmoud T, Ito Y. Efficacy of everolimus with exemestane versus exemestane alone in Asian patients with HER2-negative, hormone-receptor-positive breast cancer in BOLERO-2. Breast Cancer. 2014 Nov;21(6):703-14. doi: 10.1007/s12282-013-0444-8. Epub 2013 Feb 13.

    PubMed 23404211

  • Baselga J, Campone M, Piccart M, Burris HA 3rd, Rugo HS, Sahmoud T, Noguchi S, Gnant M, Pritchard KI, Lebrun F, Beck JT, Ito Y, Yardley D, Deleu I, Perez A, Bachelot T, Vittori L, Xu Z, Mukhopadhyay P, Lebwohl D, Hortobagyi GN. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012 Feb 9;366(6):520-9. doi: 10.1056/NEJMoa1109653. Epub 2011 Dec 7.

    PubMed 22149876

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Everolimus and Exemestane in people with Breast Cancer, run by Novartis Pharmaceuticals at 200 sites in 24 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 200 sites in United States, Japan, Canada, Spain, Italy and 19 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Aug 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (PFS) Based on Local Radiology Review of Tumor Assessments. (time frame: 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 19 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00863655, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 May 2017.

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