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 (BOLERO-2)

March 21, 2017 updated by: Novartis Pharmaceuticals

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

724

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Queensland
      • Nambour, Queensland, Australia, 4560
        • Novartis Investigative Site
      • Redcliffe, Queensland, Australia, 4020
        • Novartis Investigative Site
    • South Australia
      • Bedford Park, South Australia, Australia, 5042
        • Novartis Investigative Site
    • Victoria
      • Parkville, Victoria, Australia, 3050
        • Novartis Investigative Site
      • Parkville, Victoria, Australia, 3002
        • Novartis Investigative Site
    • Western Australia
      • Subiaco, Western Australia, Australia, 6008
        • Novartis Investigative Site
  • Austria
      • Innsbruck, Austria, A-6020
        • Novartis Investigative Site
      • Linz, Austria, A-4010
        • Novartis Investigative Site
      • Salzburg, Austria, 5020
        • Novartis Investigative Site
      • Wels, Austria, A-4600
        • Novartis Investigative Site
      • Wien, Austria, A-1090
        • Novartis Investigative Site
  • Belgium
      • Brussel, Belgium, 1090
        • Novartis Investigative Site
      • Bruxelles, Belgium, 1000
        • Novartis Investigative Site
      • Leuven, Belgium, 3000
        • Novartis Investigative Site
      • Liege, Belgium, 4000
        • Novartis Investigative Site
      • Sint-Niklaas, Belgium, 9100
        • Novartis Investigative Site
      • Wilrijk, Belgium, 2610
        • Novartis Investigative Site
  • Brazil
    • BA
      • Salvador, BA, Brazil, 41825-010
        • Novartis Investigative Site
    • MG
      • Uberlândia, MG, Brazil, 38408-150
        • Novartis Investigative Site
    • RJ
      • Rio de Janeiro, RJ, Brazil, 20230-130
        • Novartis Investigative Site
    • RS
      • Porto Alegre, RS, Brazil, 90560-030
        • Novartis Investigative Site
    • SP
      • São Paulo, SP, Brazil, 01246-000
        • Novartis Investigative Site
  • Canada
      • Quebec, Canada, G1S 4L8
        • Novartis Investigative Site
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N2
        • Novartis Investigative Site
    • New Brunswick
      • Moncton, New Brunswick, Canada, E1C 6Z8
        • Novartis Investigative Site
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 2Y9
        • Novartis Investigative Site
    • Ontario
      • Cambridge, Ontario, Canada, N1R 3G2
        • Novartis Investigative Site
      • London, Ontario, Canada, N6A 4L6
        • Novartis Investigative Site
      • Newmarket, Ontario, Canada, J7Y 2P9
        • Novartis Investigative Site
      • St. Catharines, Ontario, Canada, L2S 0A9
        • Novartis Investigative Site
      • Toronto, Ontario, Canada, M4C 3E7
        • Novartis Investigative Site
      • Toronto, Ontario, Canada, M4N 3M5
        • Novartis Investigative Site
      • Weston, Ontario, Canada, M9N 1N8
        • Novartis Investigative Site
    • Quebec
      • Greenfield Park, Quebec, Canada, J4V 2H1
        • Novartis Investigative Site
      • Montreal, Quebec, Canada, H2W 1T8
        • Novartis Investigative Site
      • Montreal, Quebec, Canada, H2W 1S6
        • Novartis Investigative Site
      • Montreal, Quebec, Canada, H4J 1C5
        • Novartis Investigative Site
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • Novartis Investigative Site
  • Czech Republic
      • Brno, Czech Republic, 656 53
        • Novartis Investigative Site
      • Praha, Czech Republic, 14044
        • Novartis Investigative Site
    • CZE
      • Olomouc, CZE, Czech Republic, 775 20
        • Novartis Investigative Site
  • Egypt
      • Alexandria, Egypt
        • Novartis Investigative Site
      • Cairo, Egypt
        • Novartis Investigative Site
      • Menoufiya, Egypt
        • Novartis Investigative Site
  • France
      • La Roche sur Yon Cedex, France, 85925
        • Novartis Investigative Site
      • Le Mans, France, 72000
        • Novartis Investigative Site
      • Lyon Cedex, France, 69373
        • Novartis Investigative Site
      • Marseille, France, 13008
        • Novartis Investigative Site
      • Paris, France, 75010
        • Novartis Investigative Site
      • Rouen, France, 76000
        • Novartis Investigative Site
      • Rouen Cedex 1, France, 76038
        • Novartis Investigative Site
      • Saint-Herblain Cédex, France, 44805
        • Novartis Investigative Site
      • Saint-Nazaire, France, 44600
        • Novartis Investigative Site
  • Germany
      • Berlin, Germany, 10098
        • Novartis Investigative Site
      • Duesseldorf, Germany, 40225
        • Novartis Investigative Site
      • Frankfurt, Germany, 60389
        • Novartis Investigative Site
      • Mannheim, Germany, 68165
        • Novartis Investigative Site
      • Muenchen, Germany, 81377
        • Novartis Investigative Site
      • Muenchen, Germany, 80637
        • Novartis Investigative Site
      • Muenster, Germany, 48149
        • Novartis Investigative Site
      • Trier, Germany, 54290
        • Novartis Investigative Site
  • Hong Kong
      • Hong Kong SAR, Hong Kong
        • Novartis Investigative Site
  • Hungary
      • Budapest, Hungary, H-1122
        • Novartis Investigative Site
      • Szeged, Hungary, H-6720
        • Novartis Investigative Site
      • Szolnok, Hungary, H-5000
        • Novartis Investigative Site
  • Italy
    • BR
      • Brindisi, BR, Italy, 72100
        • Novartis Investigative Site
    • CT
      • Catania, CT, Italy, 95100
        • Novartis Investigative Site
    • FI
      • Antella - Bagno a Ripoli, FI, Italy, 50011
        • Novartis Investigative Site
    • GE
      • Genova, GE, Italy, 16132
        • Novartis Investigative Site
    • MC
      • Macerata, MC, Italy, 62100
        • Novartis Investigative Site
    • PG
      • Perugia, PG, Italy, 06129
        • Novartis Investigative Site
    • TO
      • Torino, TO, Italy, 10126
        • Novartis Investigative Site
    • TR
      • Terni, TR, Italy, 05100
        • Novartis Investigative Site
    • VA
      • Varese, VA, Italy, 21100
        • Novartis Investigative Site
    • Va
      • Saronno, Va, Italy, 21047
        • Novartis Investigative Site
  • Japan
      • Fukuoka, Japan, 811-1395
        • Novartis Investigative Site
      • Kagoshima, Japan, 892-0833
        • 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
    • Ehime
      • Matsuyama, Ehime, Japan, 791-0280
        • Novartis Investigative Site
    • Fukuoka
      • 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
      • Kyoto-city, Kyoto, Japan, 606-8507
        • Novartis Investigative Site
    • Osaka
      • Suita-city, Osaka, Japan, 565-0871
        • Novartis Investigative Site
    • Saitama
      • Hidaka, Saitama, Japan, 350-1298
        • Novartis Investigative Site
      • Kitaadachi-gun, Saitama, Japan, 362-0806
        • Novartis Investigative Site
    • Tokyo
      • Bunkyo-ku, Tokyo, Japan, 113-8677
        • Novartis Investigative Site
      • Chuo-ku, Tokyo, Japan, 104-0045
        • Novartis Investigative Site
      • Chuo-ku, Tokyo, Japan, 104-8560
        • Novartis Investigative Site
      • Koto, Tokyo, Japan, 135-8550
        • Novartis Investigative Site
  • Korea, Republic of
      • Seoul, Korea, Republic of, 01812
        • Novartis Investigative Site
    • Jeollanam-do
      • Hwasun-gun, Jeollanam-do, Korea, Republic of, 58128
        • Novartis Investigative Site
    • Korea
      • Seoul, Korea, Korea, Republic of, 03722
        • Novartis Investigative Site
  • Netherlands
      • Alkmaar, Netherlands, 1815 JD
        • Novartis Investigative Site
      • Amsterdam, Netherlands, 1090 HM
        • Novartis Investigative Site
      • Den Haag, Netherlands, 2545 CH
        • Novartis Investigative Site
      • Dordrecht, Netherlands, 3318AT
        • Novartis Investigative Site
      • Eindhoven, Netherlands, 5631 BM
        • Novartis Investigative Site
      • Sittard-Geleen, Netherlands, 6162 BG
        • Novartis Investigative Site
  • New Zealand
      • Christchurch, New Zealand, 8001
        • Novartis Investigative Site
  • Norway
      • Lørenskog, Norway, NO-1478
        • Novartis Investigative Site
  • Poland
      • Krakow, Poland, 31-108
        • Novartis Investigative Site
      • Rzeszow, Poland, 35-021
        • Novartis Investigative Site
      • Warszawa, Poland, 04-125
        • Novartis Investigative Site
  • Spain
      • Madrid, Spain, 28041
        • Novartis Investigative Site
      • Madrid, Spain, 28046
        • Novartis Investigative Site
      • Madrid, Spain, 28033
        • Novartis Investigative Site
    • Andalucia
      • Malaga, Andalucia, Spain, 29010
        • Novartis Investigative Site
      • Sevilla, Andalucia, Spain, 41017
        • Novartis Investigative Site
    • Cataluna
      • Lleida, Cataluna, Spain, 25198
        • Novartis Investigative Site
    • Catalunya
      • Barcelona, Catalunya, Spain, 08035
        • Novartis Investigative Site
      • Terrassa, Catalunya, Spain, 08221
        • Novartis Investigative Site
    • Galicia
      • La Coruna, Galicia, Spain, 15006
        • Novartis Investigative Site
      • Santiago de Compostela, Galicia, Spain, 15706
        • Novartis Investigative Site
    • Islas Baleares
      • Mallorca, Islas Baleares, Spain, 07198
        • Novartis Investigative Site
      • Palma De Mallorca, Islas Baleares, Spain, 07120
        • Novartis Investigative Site
  • Sweden
      • Stockholm, Sweden, SE-171 76
        • Novartis Investigative Site
      • Stockholm, Sweden, SE-118 83
        • Novartis Investigative Site
      • Uppsala, Sweden, SE-751 85
        • Novartis Investigative Site
  • Thailand
      • Bangkok, Thailand, 10700
        • Novartis Investigative Site
      • Bangkok, Thailand, 10400
        • Novartis Investigative Site
      • Chiang Mai, Thailand, 50200
        • Novartis Investigative Site
      • Songkla, Thailand, 90110
        • Novartis Investigative Site
  • Turkey
      • Altunizade, Turkey, 34662
        • Novartis Investigative Site
      • Ankara, Turkey, 06100
        • Novartis Investigative Site
      • Izmir, Turkey, 35040
        • Novartis Investigative Site
  • United Kingdom
      • Cardiff, United Kingdom, CF14 2TL
        • Novartis Investigative Site
      • Nottingham, United Kingdom, NG5 1PB
        • Novartis Investigative Site
      • Sheffield, United Kingdom, S10 2SJ
        • Novartis Investigative Site
      • Southampton, United Kingdom, SO16 6YD
        • Novartis Investigative Site
    • Chelmsford
      • Broomfield, Chelmsford, United Kingdom, CM1 7ET
        • Novartis Investigative Site
    • Cornwall
      • Truro, Cornwall, United Kingdom, TR1 3LJ
        • Novartis Investigative Site
  • United States
    • Arizona
      • Chandler, Arizona, United States, 85224
        • Ironwood Cancer and Research Centers
    • Arkansas
      • Fayetteville, Arkansas, United States, 72703
        • Highlands Oncology Group DeptofHighlandsOncologyGrp(2)
    • California
      • Anaheim, California, United States, 92807
        • Kaiser Permanente Medical Group Kaiser Permanente-Moanalua M.C
      • Bakersfield, California, United States, 93309
        • Comprehensive Blood and Cancer Center Dept. of CBCC (3)
      • Fresno, California, United States, 93720
        • Cancer Care Associates Dept.ofCancerCareAssoc. (2)
      • Grass Valley, California, United States, 95945
        • Grass Valley Hematology Oncology Medical Group Dept. of Grass Valley Hem/Onc
      • La Jolla, California, United States, 92121
        • Scripps Clinic SC
      • Los Angeles, California, United States, 90025
        • The Angeles Clinic and Research Institute
      • Los Angeles, California, United States, 90053
        • USC/Kenneth Norris Comprehensive Cancer Center Regulatory Contact 3
      • San Diego, California, United States, 92123
        • Sharp Memorial Hospital SharpClinicalOncologyResearch
      • San Francisco, California, United States, 94101
        • University of California San Francisco UCSF Medical Center
      • Santa Monica, California, United States, 90404
        • Premiere Oncology/Pinnacle Oncology Hematology Dept.ofPremiereOncologyAZ
      • Santa Rosa, California, United States, 94503
        • St Joseph Heritage Healthcare Dept. of RRMG (4)
    • Florida
      • Boca Raton, Florida, United States, 33248
        • Comprehensive Cancer Center - Boca Raton Deerfield Beach
      • Davie, Florida, United States, 33328
        • Florida Cancer Research Institute
      • Fort Myers, Florida, United States, 33901
        • 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)
      • West Palm Beach, Florida, United States, 33401
        • Palm Beach Cancer Institute
      • Zephyrhills, Florida, United States, 33542
        • Florida Medical Clinic PA Dept.ofFloridaMedicalClinic
    • Georgia
      • Decatur, Georgia, United States, 30033
        • Georgia Cancer Specialists. Drug Ship
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center Study Coordinator
      • Park Ridge, Illinois, United States, 60068-0736
        • Oncology Specialists, SC Dept.of Oncology Specialists
    • Indiana
      • Indianapolis, Indiana, United States, 46260
        • Hematology Oncology of Indiana
      • Lafayette, Indiana, United States, 47905
        • Horizon Oncology Center
    • Kansas
      • Wichita, Kansas, United States, 67214-3728
        • Cancer Center of Kansas Dept.ofCancerCtr.ofKansas
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • University of Louisville / James Graham Brown Cancer Center SC
    • Louisiana
      • Baton Rouge, Louisiana, United States, 70808
        • Hematology Oncology Clinic Hematology Oncology Clinic (2)
      • Metairie, Louisiana, United States, 70006
        • Crescent City Research Consortium, LLC Dept of Hem&Onc Specialist - 2
    • Maryland
      • Annapolis, Maryland, United States, 21401
        • Anne Arundel Health System Research Institute Wayson Pavilion
      • Baltimore, Maryland, United States, 21237-3998
        • Weinberg Cancer Institute at Franklin Square Hospital
      • Baltimore, Maryland, United States, 21202
        • Mercy Medical Center Medical Oncology & Hematology
      • Baltimore, Maryland, United States, 21237
        • Maryland Hematology/Oncology Associates, P.A.
      • Frederick, Maryland, United States, 21701
        • Frederick Memorial Hospital Dept. of FMH-IRB
      • Silver Spring, Maryland, United States, 20910
        • Holy Cross Hospital Holy Cross
    • Massachusetts
      • Burlington, Massachusetts, United States, 01805
        • Lahey Clinic Dept of Lahey Clinic (2)
    • Minnesota
      • Edina, Minnesota, United States, 55435
        • Fairview Southdale Medical Oncology Clinic
    • Missouri
      • St. Louis, Missouri, United States, 63141
        • St. Louis Cancer & Breast Institute Dept.ofSt.LouisCancer&Breast
    • Nebraska
      • Lincoln, Nebraska, United States, 68510
        • Southeast Nebraska Oncology Cancer Center
    • New Jersey
      • Cherry Hill, New Jersey, United States, 08003
        • Regional Cancer Care Associates Dept. of the CCHD
      • Elizabeth, New Jersey, United States, 07207
        • Trinitas Comprehensive Cancer Center Dept. of Trinitas
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • University of New Mexico Cancer Research Center Dept of UNM Cancer & Research
    • New York
      • Lake Success, New York, United States, 11042
        • Clinical Research Alliance Dept.ofArenaOncologyAssoc(2)
      • Lake Success, New York, United States, 11042
        • ProHealth Care
      • New York, New York, United States, 10003
        • Beth Israel Medical Center Dept.ofBeth Israel Med. Ctr(2)
      • New York, New York, United States, 10021
        • Weill Cornell Medical College Weill Cornell Med. Ctr.
      • Nyack, New York, United States, 10960
        • Hematology Oncology Association of Rockland
    • North Carolina
      • Washington, North Carolina, United States, 27889
        • Marion L. Shepard Cancer Center
    • Oklahoma
      • Lawton, Oklahoma, United States, 73505
        • Cancer Centers of Southwest Oklahoma Cancer Research Dept.of Southwest Oklahoma
      • Tulsa, Oklahoma, United States, 74136
        • Cancer Care Associates SC
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033-0850
        • Penn State University / Milton S. Hershey Medical Center Division of Oncology (2)
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina -Hollings Cancer Center Dept. MUSC/HollingsCancerCtr
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute Dept.ofSarahCannonCancerCtr(5)
    • Texas
      • Dallas, Texas, United States, 75390-8852
        • University of Texas Southwestern Medical Center SimmonsComprehensiveCancerCtr.
      • Fort Worth, Texas, United States, 76104
        • The Center for Cancer and Blood Disorders Dept. of The Ctr for C & BD(2)
      • Houston, Texas, United States, 77030-4009
        • University of Texas/MD Anderson Cancer Center Dept.ofMDAndersonCancerCtr(2)
      • Richardson, Texas, United States, 75080
        • Hope Oncology HOPE Richardson
    • Utah
      • Ogden, Utah, United States, 84403-3105
        • Northern Utah Cancer Associates SC
      • Provo, Utah, United States, 84604
        • Central Utah Clinic CRAD001Y2301
      • Salt Lake City, Utah, United States, 84106
        • Utah Cancer Specialists Dept.of Utah Cancer Spec. (2)
      • Salt Lake City, Utah, United States, 84112
        • University of Utah / Huntsman Cancer Institute Dept.ofHuntsmanCancerInst.(2)
    • Virginia
      • Reston, Virginia, United States, 20190
        • Medical Oncology & Hematology Associates of Northern VA Med. Onc&Hem Assoc. of No.VA
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Hospital & Clinics UW ComprehensiveCancerCtr(2)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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 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.

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Everolimus + Exemestane
Everolimus 10 mg daily in combination with exemestane 25 mg daily
Drug: Exemestane
Exemestane 25 mg orally daily.
Drug: Everolimus
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.
Other Names:
  • RAD001
ACTIVE_COMPARATOR: Placebo + Exemestane
Placebo of everolimus in combination with exemestane 25 mg daily
Drug: Exemestane
Exemestane 25 mg orally daily.
Drug: Everolimus Placebo
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS) by Number of Deaths
Time Frame: up to 53 months
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.
up to 53 months
Overall Survival (OS) by Median
Time Frame: up to 53 months
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.
up to 53 months
Overall Response Rate (ORR)
Time Frame: up to 21 months
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.
up to 21 months
Clinical Benefit Rate (CBR)
Time Frame: up to 21 months
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.
up to 21 months
Proportion of Patients With no Deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG PS) Using Kaplan-Meier
Time Frame: 2, 4, 6, 9 months
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.
2, 4, 6, 9 months
Patient-reported Outcomes (PROs): Time to Deterioration of PRO Scores Using Kaplan Meier - EORTC QLQ-C30
Time Frame: Up to 21 months
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.
Up to 21 months
Proportion of Patients With Having no Overall Response Based on Investigator Assessment
Time Frame: 2, 4, 6, 9 months
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.
2, 4, 6, 9 months
Duration of Response (Among Participants With Best Overall Response of CR or PR) Estimated Per Kaplan-Meier
Time Frame: 21 months
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.
21 months
Everolimus Concentrations at Week 4
Time Frame: pre-dose, 2 hours post-dose
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.
pre-dose, 2 hours post-dose
Exemestane Concentrations at Week 4
Time Frame: predose, 2 hours post-dose
Characterize the PK of exemestane in combination with or without everolimus using Cmin and C2h at week 4 in a small group of patients.
predose, 2 hours post-dose
Estradiol Plasma Concentrations
Time Frame: Baseline, Week 4
Compare estradiol concentrations from baseline to week 4 in both treatment arms.
Baseline, Week 4

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

June 3, 2009

Primary Completion (ACTUAL)

December 4, 2014

Study Completion (ACTUAL)

December 4, 2014

Study Registration Dates

First Submitted

March 16, 2009

First Submitted That Met QC Criteria

March 17, 2009

First Posted (ESTIMATE)

March 18, 2009

Study Record Updates

Last Update Posted (ACTUAL)

May 2, 2017

Last Update Submitted That Met QC Criteria

March 21, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CRAD001Y2301
  • 2008-008698-69 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe