Daily Everolimus in Combination With Trastuzumab and Vinorelbine in HER2/Neu Positive Women With Locally Advanced or Metastatic Breast Cancer
BOLERO-3
A Randomized Phase III, Double-blind, Placebo-controlled Multicenter Trial of Daily Everolimus in Combination With Trastuzumab and Vinorelbine, in Pretreated Women With HER2/Neu Over-expressing Locally Advanced or Metastatic Breast Cancer.
2 other identifiers
interventional
569
21 countries
161
Brief Summary
This phase III, double-blind, placebo-controlled multinational study will assess the combination everolimus, vinorelbine, and trastuzumab compared to the combination vinorelbine and trastuzumab with respect to progressive-free survival and over survival in HER2/neu positive women with locally advanced or metastatic breast cancer who are resistant to trastuzumab and have been pre-treated with a taxane.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Oct 2009
Longer than P75 for phase_3
161 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 1, 2009
CompletedFirst Submitted
Initial submission to the registry
November 2, 2009
CompletedFirst Posted
Study publicly available on registry
November 4, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2015
CompletedResults Posted
Study results publicly available
April 5, 2017
CompletedApril 5, 2017
February 1, 2017
5.7 years
November 2, 2009
June 10, 2016
February 20, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progressive-free Survival (PFS) Per Investigator Assessment
PFS was defined as the time from the date of randomization to the date of first radiologically documented tumor progression or death from any cause, whichever occurs first. PFS primary analysis performed when 415 events were reached. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Every 6 weeks until disease progression or death which ever occurred first up to about 41 months
Secondary Outcomes (8)
Overall Survival (OS)
Every 3 months until death up to 41 months
Overall Response Rate (ORR)
Every 6 weeks until disease progression or death which ever occurred first up to about 41 months
Clinical Benefit Rate (CBR)
Every 6 weeks until disease progression or death which ever occurred first up to about 41 months
Median Time to Deterioration of the ECOG Performance Status Score
baseline, until disease progression or death up to about 41 months
PRO: Time to Deterioration in Global Health Status/QoL Domain Score of the European Organization for the Research and Treatment of Cancer (EORTC)-Core Quality of Life Questionnaire (QLQ-C30) (by at Least 10%)
Baseline, until disease progression or death up to about 41 months
- +3 more secondary outcomes
Study Arms (2)
Everolimus + vinorelbine + trastuzumab
EXPERIMENTALOral everolimus (5 mg/day) + intravenous vinorelbine (25 mg/m2 weekly) + intravenous trastuzumab (2 mg/kg weekly following a 4 mg/kg loading dose on Day 1 of Cycle 1 only)
placebo + vinorelbine + trastuzumab
PLACEBO COMPARATOROral daily matching placebo + intravenous vinorelbine (25 mg/m2 weekly) + intravenous trastuzumab (2 mg/kg weekly following a 4 mg/kg loading dose on Day 1 of Cycle 1 only
Interventions
Oral everolimus was taken once 5 mg/day (2 × 2.5 mg tablets) and were packaged into blister packs.
Oral everolimus placebo was taken once 5 mg/day (2 × 2.5 mg tablets) and were packaged into blister packs.
intravenous vinorelbine (25 mg/m2 weekly)
intravenous trastuzumab (2 mg/kg weekly following a 4 mg/kg loading dose on Day 1 of Cycle 1 only)
Eligibility Criteria
You may qualify if:
- Histologically or cytologically confirmed invasive breast carcinoma with locally recurrent or radiological evidence of metastatic disease. Locally recurrent disease must not be amenable to resection with curative intent.
- HER2+ status defined as IHC 3+ staining or in situ hybridization positive
- Patients with resistance to trastuzumab
- Prior taxane therapy
- Patients with an ECOG performance status of 0 - 2
- Patients with measurable disease as per RECIST criteria
- Documentation of negative pregnancy test for patients of child bearing potential prior to enrollment within 7 days prior to randomization. Sexually active pre-menopausal women must use adequate contraceptive measures, excluding estrogen containing contraceptives, while on study;
- Patients must meet laboratory criteria defined in the study within 21 days prior to randomization
You may not qualify if:
- Prior mTOR inhibitors or vinca alkaloid agents for the treatment of cancer
- More than three prior chemotherapy lines for advanced disease.
- Symptomatic CNS metastases or evidence of leptomeningeal disease. Previously treated asymptomatic CNS metastases are allowed provided that the last treatment for CNS metastases was completed \>8 weeks prior to randomization
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus
- Peripheral neuropathy ≥ grade 2 at randomization
- Active cardiac disease
- History of cardiac dysfunction
- Any malignancy within 5 years prior to randomization, with the exception of adequately treated in-situ carcinoma of the cervix uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer
- Known hypersensitivity to any study medication
- Breastfeeding or pregnant
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (161)
University of Arizona / Cancer Center AZ Onc Assoc
Tucson, Arizona, 85724, United States
University of Arizona / Cancer Center Deptof Uof A/Arizona Cancer(3)
Tucson, Arizona, 85724, United States
University of California San Diego - Moores Cancer Center La Jolla - UCSD Moores Cancer
La Jolla, California, 92093-0658, United States
Rocky Mountain Cancer Centers RMCC
Greenwood Village, Colorado, United States
Georgetown University/Lombardi Cancer Center Dept.of Lombardi CancerCtr (3)
Washington D.C., District of Columbia, 20007-2197, United States
Comprehensive Cancer Center - Boca Raton Deerfield Beach
Boca Raton, Florida, 33248, United States
Comprehensive Cancer Center - Boca Raton Dept.of BocaRatonCompCanCtr
Boca Raton, Florida, 33248, United States
Florida Cancer Specialists DeptofFloridaCancerSpecialists
Fort Myers, Florida, 33916, United States
Memorial Hospital Memorial Cancer Institute
Hollywood, Florida, 33021, United States
MD Anderson Cancer Center - Orlando Dept.ofMDACC-Orlando(2)
Orlando, Florida, 32806, United States
Emory University School of Medicine/Winship Cancer Institute Dept.of WinshipCancerInst. (2)
Atlanta, Georgia, 30322, United States
North Shore University Health System NSU
Evanston, Illinois, 60201, United States
Kansas City Cancer Center KCCC- South (2)
Overland Park, Kansas, 66210, United States
Maryland Oncology Hematology
Owning Mills, Maryland, 21117,, United States
Park Nicollet Institute Dept. of Park Nicollet
Saint Louis Park, Minnesota, 55416, United States
St. Louis University Cancer Center SLU Cancer Center
St Louis, Missouri, 63110, United States
University of Nebraska Medical Center Unv Nebraska Med Ctr (2)
Omaha, Nebraska, 68198, United States
Comprehensive Cancer Centers of Nevada CCC of Nevada Henderson (4)
Las Vegas, Nevada, 89109, United States
Nevada Cancer Institute Dept. of Nevada Cancer (3)
Las Vegas, Nevada, 89135, United States
Overlook Hospital - Carol G Simon Cancer Center Carol G Simon
Summit, New Jersey, 07901, United States
Clinical Research Alliance Dept.ofArenaOncologyAssoc(2)
Lake Success, New York, 11042, United States
Duke University Medical Center Dept. of DUMC (2)
Durham, North Carolina, 27710, United States
Northwest Cancer Specialists Tutlatin
Portland, Oregon, 97210, United States
University of Pittsburgh Cancer Institute DeptofMageeWomen'sHospital(2)
Pittsburgh, Pennsylvania, 15232, United States
The Jones Clinic Dept .of The Jones Clinic (3)
Germantown, Tennessee, 38138, United States
Sarah Cannon Research Institute Dept.ofSarahCannonCancerCtr(6)
Nashville, Tennessee, 37203, United States
Texas Cancer Center ( Medical City Dallas Hospital) Dept. of Texas Cancer Ctr. (2)
Dallas, Texas, 75230, United States
Texas Oncology Presbyterian Hospital (2)
Dallas, Texas, 75246, United States
Texas Oncology Texas Onc - Amarillo
Dallas, Texas, 75246, United States
Texas Oncology Texas Oncology - Sammons
Dallas, Texas, 75246, United States
Texas Oncology Midtown
Dallas, Texas, 75251, United States
University of Texas Southwestern Medical Center University of TX SW Med Ctr(2)
Dallas, Texas, 75390-8852, United States
University of Texas/MD Anderson Cancer Center SC-5
Houston, Texas, 77030-4009, United States
Baylor College of Medicine Baylor
Houston, Texas, 77030, United States
Longview Cancer Center Longview Cancer Center (2)
Longview, Texas, 75601, United States
Cancer Care Centers of South Texas / HOAST CCC of So. TX- San Antonio(2)
San Antonio, Texas, 78229, United States
South Texas Oncology and Hematology, PA South Texas Oncology (2)
San Antonio, Texas, 78258, United States
Tyler Cancer Center Dept.ofTylerCancerCtr. (2)
Tyler, Texas, 75702, United States
Utah Cancer Specialists Utah Cancer (2)
Salt Lake City, Utah, 84106, United States
Virginia Cancer Specialists Fairfax No.VA (2)
Fairfax, Virginia, 22031, United States
Virginia Oncology Associates Dept. of VOA (2)
Norfolk, Virginia, 23502, United States
Swedish Cancer Institute Swedish Cancer Institute
Seattle, Washington, 98104, United States
Green Bay Oncology Green Bay Oncology
Green Bay, Wisconsin, 54301, United States
Novartis Investigative Site
C A B A, Buenos Aires, C1019ABS, Argentina
Novartis Investigative Site
Caba, Buenos Aires, C1050AAK, Argentina
Novartis Investigative Site
Mar del Plata, Buenos Aires, 7600, Argentina
Novartis Investigative Site
Quilmes, Buenos Aires, B1878DVB, Argentina
Novartis Investigative Site
Córdoba, Córdoba Province, X5002AOQ, Argentina
Novartis Investigative Site
Posadas, Misiones Province, Argentina
Novartis Investigative Site
Rosario, Sante Fe, S200KZE, Argentina
Novartis Investigative Site
San Miguel de Tucumán, Tucumán Province, T4000IAK, Argentina
Novartis Investigative Site
Rio Negro, Viedma, 8500, Argentina
Novartis Investigative Site
Kogarah, New South Wales, 2217, Australia
Novartis Investigative Site
St Leonards, New South Wales, 2065, Australia
Novartis Investigative Site
South Brisbane, Queensland, 4101, Australia
Novartis Investigative Site
Southport, Queensland, 4215, Australia
Novartis Investigative Site
Hobart, Tasmania, 7000, Australia
Novartis Investigative Site
East Bentleigh, Victoria, 3165, Australia
Novartis Investigative Site
Brussels, 1000, Belgium
Novartis Investigative Site
Brussels, 1090, Belgium
Novartis Investigative Site
Liège, 4000, Belgium
Novartis Investigative Site
Namur, 5000, Belgium
Novartis Investigative Site
Sint-Niklaas, 9100, Belgium
Novartis Investigative Site
Shanghai, Shanghai Municipality, 200032, China
Novartis Investigative Site
Hangzhou, Zhejiang, 310022, China
Novartis Investigative Site
Beijing, 100021, China
Novartis Investigative Site
Beijing, 100039, China
Novartis Investigative Site
Guangzhou, 510060, China
Novartis Investigative Site
Shanghai, 200025, China
Novartis Investigative Site
Nový Jičín, 741 01, Czechia
Novartis Investigative Site
Olomouc, 775 20, Czechia
Novartis Investigative Site
Prague, 150 00, Czechia
Novartis Investigative Site
Bayonne, 64100, France
Novartis Investigative Site
Besançon, 25030, France
Novartis Investigative Site
Hyères, 83400, France
Novartis Investigative Site
La Chaussée-Saint-Victor, 41260, France
Novartis Investigative Site
La Roche-sur-Yon, 85925, France
Novartis Investigative Site
Nice, 06189, France
Novartis Investigative Site
Saint-Brieuc Cédex, 22015, France
Novartis Investigative Site
Villejuif, 94805, France
Novartis Investigative Site
Mainz, Germany, 55131, Germany
Novartis Investigative Site
Berlin, 14195, Germany
Novartis Investigative Site
Frankfurt, 60590, Germany
Novartis Investigative Site
Gerlingen, 70839, Germany
Novartis Investigative Site
Halle, 06120, Germany
Novartis Investigative Site
Hamburg, 20249, Germany
Novartis Investigative Site
Homburg, 66421, Germany
Novartis Investigative Site
Kiel, 24105, Germany
Novartis Investigative Site
Magdeburg, 39108, Germany
Novartis Investigative Site
Minden, 32429, Germany
Novartis Investigative Site
München, 80638, Germany
Novartis Investigative Site
Recklinghausen, 45657, Germany
Novartis Investigative Site
Velbert, 42551, Germany
Novartis Investigative Site
Athens, Greece, 18547, Greece
Novartis Investigative Site
Heraklion Crete, Greece, 711 10, Greece
Novartis Investigative Site
Athens, GR, 151 23, Greece
Novartis Investigative Site
Patra - RIO, GR, 265 04, Greece
Novartis Investigative Site
Thessaloniki, GR, 546 45, Greece
Novartis Investigative Site
Thessaloniki, GR, 564 03, Greece
Novartis Investigative Site
Győr, Hungary, H-9023, Hungary
Novartis Investigative Site
Budapest, 1062, Hungary
Novartis Investigative Site
Budapest, H-1122, Hungary
Novartis Investigative Site
Debrecen, 4032, Hungary
Novartis Investigative Site
Jerusalem, 9112001, Israel
Novartis Investigative Site
Petah Tikva, 49100, Israel
Novartis Investigative Site
Ramat Gan, 5266202, Israel
Novartis Investigative Site
Tel Aviv, 6423906, Israel
Novartis Investigative Site
Catania, CT, 95125, Italy
Novartis Investigative Site
Milan, MI, 20132, Italy
Novartis Investigative Site
Milan, MI, 20133, Italy
Novartis Investigative Site
Milan, MI, 20157, Italy
Novartis Investigative Site
Pavia, PV, 27100, Italy
Novartis Investigative Site
Sondrio, SO, 23100, Italy
Novartis Investigative Site
Nagoya, Aichi-ken, 464-8681, Japan
Novartis Investigative Site
Kashiwa, Chiba, 277-8577, Japan
Novartis Investigative Site
Fukuoka, Fukuoka, 811-1395, Japan
Novartis Investigative Site
Maebashi, Gunma, 371-8511, Japan
Novartis Investigative Site
Sapporo, Hokkaido, 003-0804, Japan
Novartis Investigative Site
Yokohama, Kanagawa, 241-8515, Japan
Novartis Investigative Site
Kumamoto, Kumamoto, 860-8556, Japan
Novartis Investigative Site
Kyoto, Kyoto, 606-8507, Japan
Novartis Investigative Site
Osaka, Osaka, 537-8511, Japan
Novartis Investigative Site
Osaka, Osaka, 540-0006, Japan
Novartis Investigative Site
Suita, Osaka, 565-0871, Japan
Novartis Investigative Site
Bunkyo-ku, Tokyo, 113-8431, Japan
Novartis Investigative Site
Koto, Tokyo, 135-8550, Japan
Novartis Investigative Site
León, Guanajuato, 37000, Mexico
Novartis Investigative Site
Mexico City, Mexico City, 04980, Mexico
Novartis Investigative Site
Lublin, 20-090, Poland
Novartis Investigative Site
Warsaw, 02-781, Poland
Novartis Investigative Site
Singapore, Singapore, 169610, Singapore
Novartis Investigative Site
Bratislava, 83310, Slovakia
Novartis Investigative Site
Košice, 040 91, Slovakia
Novartis Investigative Site
Córdoba, Andalusia, 14004, Spain
Novartis Investigative Site
Jaén, Andalusia, 23007, Spain
Novartis Investigative Site
Seville, Andalusia, 41014, Spain
Novartis Investigative Site
Barcelona, Barcelona, 08041, Spain
Novartis Investigative Site
Sabadell, Barcelona, 08208, Spain
Novartis Investigative Site
Barcelona, Catalonia, 08036, Spain
Novartis Investigative Site
A Coruña, Galicia, 15006, Spain
Novartis Investigative Site
A Coruña, Galicia, 15009, Spain
Novartis Investigative Site
Madrid, Madrid, 28007, Spain
Novartis Investigative Site
Madrid, Madrid, 28034, Spain
Novartis Investigative Site
Madrid, Madrid, 28040, Spain
Novartis Investigative Site
Majadahonda, Madrid, 28222, Spain
Novartis Investigative Site
San Cristóbal de La Laguna, Santa Cruz de Tenerife, 38320, Spain
Novartis Investigative Site
Valencia, Valencia, 46009, Spain
Novartis Investigative Site
Zaragoza, Zaragoza, 50009, Spain
Novartis Investigative Site
Bangkok, 10330, Thailand
Novartis Investigative Site
Bangkok, 10400, Thailand
Novartis Investigative Site
Songkhla, 90110, Thailand
Novartis Investigative Site
Ankara, Turkey, 06100, Turkey (Türkiye)
Novartis Investigative Site
Izmir, Turkey, 35040, Turkey (Türkiye)
Novartis Investigative Site
Fatih / Istanbul, 34098, Turkey (Türkiye)
Novartis Investigative Site
Truro, Cornwall, TR1 3LJ, United Kingdom
Novartis Investigative Site
Surrey, England, GU2 7XX, United Kingdom
Novartis Investigative Site
Bournemouth, BH7 7DW, United Kingdom
Novartis Investigative Site
Leeds, LS9 7TF, United Kingdom
Novartis Investigative Site
London, EC1A 7BE, United Kingdom
Novartis Investigative Site
Manchester, M20 4BX, United Kingdom
Novartis Investigative Site
Plymouth, PL6 8DH, United Kingdom
Related Publications (1)
Andre F, O'Regan R, Ozguroglu M, Toi M, Xu B, Jerusalem G, Masuda N, Wilks S, Arena F, Isaacs C, Yap YS, Papai Z, Lang I, Armstrong A, Lerzo G, White M, Shen K, Litton J, Chen D, Zhang Y, Ali S, Taran T, Gianni L. Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2014 May;15(6):580-91. doi: 10.1016/S1470-2045(14)70138-X. Epub 2014 Apr 14.
PMID: 24742739DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
All randomized patients were included in the FAS. Seven patients (4 in the everolimus arm \& 3 in the placebo arm) were randomized but never received treatment \& were therefore excluded from the Safety Set.
Results Point of Contact
- Title
- Study Director
- Organization
- Novartis Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 2, 2009
First Posted
November 4, 2009
Study Start
October 1, 2009
Primary Completion
June 1, 2015
Study Completion
June 1, 2015
Last Updated
April 5, 2017
Results First Posted
April 5, 2017
Record last verified: 2017-02