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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01007942
First received: November 2, 2009
Last updated: June 17, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
HER2/Neu Over-expressing Locally Advanced Breast Cancer
Metastatic Breast Cancer
Drug: everolimus, vinorelbine, trastuzumab
Drug: Placebo + vinorelbine + trastuzumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Progressive-free survival (PFS), 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. [ Time Frame: Every 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival (OS), defined as the time from date of randomization to the date of death from any cause. [ Time Frame: Every 3 months ] [ Designated as safety issue: No ]
  • Overall response rate (ORR) defined as the proportion of patients whose best overall response is either complete response (CR) or partial response (PR) according to RECIST [ Time Frame: Every 6 weeks ] [ Designated as safety issue: No ]
  • Patient reported outcome (PRO) questionnaires [ Time Frame: Every 6 weeks ] [ Designated as safety issue: No ]
  • Clinical benefit rate (CBR) defined as the proportion of patients whose best overall response, according to RECIST, is either complete response (CR), a partial response (PR) or stable disease (SD) lasting for at least 24 weeks. [ Time Frame: Every 6 weeks ] [ Designated as safety issue: No ]
  • Laboratory assessments (hematology, chemistry, coagulation), AEs graded by CTCAE version 3.0 or equivalent [ Time Frame: Continuous until 28 days after the last dose of study drug ] [ Designated as safety issue: Yes ]

Enrollment: 570
Study Start Date: October 2009
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus + vinorelbine + trastuzumab Drug: everolimus, vinorelbine, trastuzumab
Placebo Comparator: placebo + vinorelbine + trastuzumab Drug: Placebo + vinorelbine + trastuzumab

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Other protocol-defined inclusion/exclusion criteria may ap

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01007942

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Locations
United States, Arizona
University of Arizona / Arizona Cancer Center AZ Onc Assoc
Tucson, Arizona, United States, 85724
University of Arizona / Arizona Cancer Center Deptof Uof A/Arizona Cancer(3)
Tucson, Arizona, United States, 85724
United States, California
University of California San Diego La Jolla - UCSD Moores Cancer
La Jolla, California, United States, 92093-0658
United States, Colorado
Rocky Mountain Cancer Centers RMCC
Greenwood Village, Colorado, United States
United States, District of Columbia
Georgetown University/Lombardi Cancer Center Dept.of Lombardi CancerCtr (3)
Washington, District of Columbia, United States, 20007-2197
United States, Florida
Comprehensive Cancer Center - Boca Raton Deerfield Beach
Boca Raton, Florida, United States, 33248
Comprehensive Cancer Center - Boca Raton Dept.of BocaRatonCompCanCtr
Boca Raton, Florida, United States, 33248
Florida Cancer Specialists DeptofFloridaCancerSpecialists
Fort Myers, Florida, United States, 33901
Memorial Hospital Memorial Cancer Institute
Hollywood, Florida, United States, 33021
MD Anderson Cancer Center - Orlando Dept.ofMDACC-Orlando(2)
Orlando, Florida, United States, 32806
United States, Georgia
Emory University School of Medicine/Winship Cancer Institute Dept.of WinshipCancerInst. (2)
Atlanta, Georgia, United States, 30322
United States, Illinois
North Shore University Health System NSU
Evanston, Illinois, United States, 60201
United States, Kansas
Kansas City Cancer Center KCCC- South (2)
Overland Park, Kansas, United States, 66210
United States, Maryland
Maryland Oncology Hematology
Owning Mills, Maryland, United States, 21117,
United States, Minnesota
Park Nicollet Institute Dept. of Park Nicollet
St. Louis Park, Minnesota, United States, 55416
United States, Missouri
St. Louis University Cancer Center SLU Cancer Center
St. Louis, Missouri, United States, 63110
United States, Nebraska
University of Nebraska Medical Center Unv Nebraska Med Ctr (2)
Omaha, Nebraska, United States, 68198
United States, Nevada
Comprehensive Cancer Centers of Nevada CCC of Nevada Henderson (4)
Las Vegas, Nevada, United States, 89109
Nevada Cancer Institute Dept. of Nevada Cancer (3)
Las Vegas, Nevada, United States, 89135
United States, New Jersey
Overlook Hospital - Carol G Simon Cancer Center Carol G Simon
Summit, New Jersey, United States, 07901
United States, New York
NYU Langone Arena Oncology Dept.ofArenaOncologyAssoc(2)
Lake Success, New York, United States, 11042
United States, North Carolina
Duke University Medical Center Dept. of DUMC (2)
Durham, North Carolina, United States, 27710
United States, Oregon
Northwest Cancer Specialists Tutlatin
Portland, Oregon, United States, 97210
United States, Pennsylvania
University of Pittsburgh Cancer Institute DeptofMageeWomen'sHospital(2)
Pittsburgh, Pennsylvania, United States, 15232
United States, Tennessee
The Jones Clinic Dept .of The Jones Clinic (3)
Germantown, Tennessee, United States, 38138
Sarah Cannon Research Institute Dept.ofSarahCannonCancerCtr(6)
Nashville, Tennessee, United States, 37203
United States, Texas
Texas Oncology, P.A. Texas Oncology - Sammons
Dallas, Texas, United States, 75246
Texas Oncology, P.A. Midtown
Dallas, Texas, United States, 75251
Texas Oncology, P.A. Presbyterian Hospital (2)
Dallas, Texas, United States, 75246
University of Texas Southwestern Medical Center University of TX SW Med Ctr(2)
Dallas, Texas, United States, 75390-8852
Texas Cancer Center ( Medical City Dallas Hospital) Dept. of Texas Cancer Ctr. (2)
Dallas, Texas, United States, 75230
Texas Oncology, P.A. Texas Onc - Amarillo
Dallas, Texas, United States, 75246
University of Texas/MD Anderson Cancer Center Dept of MD Anderson (17)
Houston, Texas, United States, 77030-4009
Baylor College of Medicine Baylor
Houston, Texas, United States, 77030
Longview Cancer Center Longview Cancer Center (2)
Longview, Texas, United States, 75601
South Texas Oncology and Hematology, PA South Texas Oncology (2)
San Antonio, Texas, United States, 78258
Cancer Care Centers of South Texas / HOAST CCC of So. TX- San Antonio(2)
San Antonio, Texas, United States, 78229
Tyler Cancer Center Dept.ofTylerCancerCtr. (2)
Tyler, Texas, United States, 75702
United States, Utah
Utah Cancer Specialists Utah Cancer (2)
Salt Lake City, Utah, United States, 84106
United States, Virginia
Virginia Cancer Specialists, PC Dept.ofFairfaxNo.VA (2)
Fairfax, Virginia, United States, 22031
Virginia Oncology Associates Dept. of VOA (2)
Norfolk, Virginia, United States, 23502
United States, Washington
Swedish Cancer Institute Swedish Cancer Institute
Seattle, Washington, United States, 98104
United States, Wisconsin
St Vincent Hospital Green Bay Oncology
Green Bay, Wisconsin, United States, 54301
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Sint-Niklaas, Belgium, 9100
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Shanghai, Shanghai, China, 200032
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Hangzhou, Zhejiang, China, 310022
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Beijing, China, 100039
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Shanghai, China, 200025
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Olomouc, Czech Republic, 775 20
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Prague 5, Czech Republic, 150 00
France
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Bayonne, France, 64100
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Besançon cedex, France, 25030
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Hyères, France, 83400
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La Chaussée St Victor, France, 41260
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La Roche sur Yon Cedex, France, 85925
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Nice Cedex 2, France, 06189
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Villejuif Cedex, France, 94805
Germany
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Berlin, Germany, 14195
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Gerlingen, Germany, 70839
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Recklinghausen, Germany, 45657
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Heraklion Crete, GR, Greece, 711 10
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Patra - RIO, GR, Greece, 265 04
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Athens, Neo Faliro, Greece, GR 18547
Hungary
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Budapest, Hungary, H-1122
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Debrecen, Hungary, 4032
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Gyor, Hungary, H-9023
Israel
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Jerusalem, Israel, 91120
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Petach Tikva, Israel, 49100
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Ramat Gan, Israel, 52621
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Tel-Aviv, Israel, 64239
Italy
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Catania, CT, Italy, 95125
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Milano, MI, Italy, 20132
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Milano, MI, Italy, 20157
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Milano, MI, Italy, 20133
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Pavia, PV, Italy, 27100
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Sondrio, SO, Italy, 23100
Japan
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Nagoya, Aichi, Japan, 464-8681
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Kashiwa, Chiba, Japan, 277-8577
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Maebashi-city, Gunma, Japan, 371-8511
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Sapporo, Hokkaido, Japan, 003-0804
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Yokohama, Kanagawa, Japan, 241-8515
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Kumamoto City, Kumamoto, Japan, 860-8556
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Kyoto-city, Kyoto, Japan, 606-8507
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Suita-city, Osaka, Japan, 565-0871
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Bunkyo-ku, Tokyo, Japan, 113-8431
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Koto, Tokyo, Japan, 135-8550
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Fukuoka, Japan, 811-1395
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Osaka, Japan, 540-0006
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Osaka, Japan, 537-8511
Mexico
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Ciudad De Mexico, Distrito Federal, Mexico, 04980
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León, Guanajuato, Mexico, 37000
Poland
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Lublin, Poland, 20-090
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Warszawa, Poland, 02-781
Singapore
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Singapore, Singapore, 169610
Slovakia
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Bratislava, Slovakia, 83310
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Kosice, Slovakia, 040 91
Spain
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Cordoba, Andalucia, Spain, 14004
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Jaen, Andalucia, Spain, 23007
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Sevilla, Andalucia, Spain, 41014
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Sabadell, Barcelona, Spain, 08208
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Barcelona, Catalunya, Spain, 08036
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Valencia, Comunidad Valenciana, Spain, 46009
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A Coruna, Galicia, Spain, 15009
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La Coruna, Galicia, Spain, 15006
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La Laguna, Las Palmas de Gran Canaria, Spain, 38320
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Majadanonda, Madrid, Spain, 28220
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Barcelona, Spain, 08025
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Madrid, Spain, 28034
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Madrid, Spain, 28040
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Madrid, Spain, 28009
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Zaragoza, Spain, 50009
Thailand
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Bangkok, Thailand, 10330
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Bangkok, Thailand, 10400
Turkey
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Ankara, Turkey, 06100
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Istanbul, Turkey, 34303
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Izmir, Turkey, 35040
United Kingdom
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Truro, Cornwall, United Kingdom, TR1 3LJ
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Surrey, England, United Kingdom, GU2 7XX
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Bournemouth, United Kingdom, BH7 7DW
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Leeds, United Kingdom, LS9 7TF
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London, United Kingdom, EC1A 7BE
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Manchester, United Kingdom, M20 4BX
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Plymouth, United Kingdom, PL6 8DH
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Additional Information:
No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01007942     History of Changes
Other Study ID Numbers: CRAD001W2301, 2008-008697-31
Study First Received: November 2, 2009
Last Updated: June 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Metastatic breast cancer
locally advanced breast cancer
HER2/neu positive breast cancer
HER2/neu over-expressing
progressive-free survival (PFS)
over survival (OS)
bolero
bolero 3
Breast cancer
everolimus
HER+
vinorelbine
herceptin
trastuzumab

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Everolimus
Sirolimus
Trastuzumab
Vinorelbine
Vinblastine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 22, 2014