Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01007942




Registration number
NCT01007942
Ethics application status
Date submitted
2/11/2009
Date registered
4/11/2009
Date last updated
5/04/2017

Titles & IDs
Public title
Daily Everolimus in Combination With Trastuzumab and Vinorelbine in HER2/Neu Positive Women With Locally Advanced or Metastatic Breast Cancer
Scientific 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.
Secondary ID [1] 0 0
2008-008697-31
Secondary ID [2] 0 0
CRAD001W2301
Universal Trial Number (UTN)
Trial acronym
BOLERO-3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HER2/Neu Over-expressing Locally Advanced Breast Cancer 0 0
Metastatic Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - everolimus
Treatment: Drugs - Placebo
Treatment: Drugs - vinorelbine
Treatment: Drugs - trastuzumab

Experimental: Everolimus + vinorelbine + trastuzumab - Oral 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 comparator: placebo + vinorelbine + trastuzumab - Oral 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


Treatment: Drugs: everolimus
Oral everolimus was taken once 5 mg/day (2 × 2.5 mg tablets) and were packaged into blister packs.

Treatment: Drugs: Placebo
Oral everolimus placebo was taken once 5 mg/day (2 × 2.5 mg tablets) and were packaged into blister packs.

Treatment: Drugs: vinorelbine
intravenous vinorelbine (25 mg/m2 weekly)

Treatment: Drugs: trastuzumab
intravenous trastuzumab (2 mg/kg weekly following a 4 mg/kg loading dose on Day 1 of Cycle 1 only)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progressive-free Survival (PFS) Per Investigator Assessment
Timepoint [1] 0 0
Every 6 weeks until disease progression or death which ever occurred first up to about 41 months
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Every 3 months until death up to 41 months
Secondary outcome [2] 0 0
Overall Response Rate (ORR)
Timepoint [2] 0 0
Every 6 weeks until disease progression or death which ever occurred first up to about 41 months
Secondary outcome [3] 0 0
Clinical Benefit Rate (CBR)
Timepoint [3] 0 0
Every 6 weeks until disease progression or death which ever occurred first up to about 41 months
Secondary outcome [4] 0 0
Median Time to Deterioration of the ECOG Performance Status Score
Timepoint [4] 0 0
baseline, until disease progression or death up to about 41 months
Secondary outcome [5] 0 0
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%)
Timepoint [5] 0 0
Baseline, until disease progression or death up to about 41 months
Secondary outcome [6] 0 0
Everolimus Blood Concentrations by Leading Dose and Time Point
Timepoint [6] 0 0
Cycle 2, Day 1
Secondary outcome [7] 0 0
Vinorelbine Blood Concentrations by Leading Dose and Time Point
Timepoint [7] 0 0
Cycle 2, Day 1
Secondary outcome [8] 0 0
Trastuzumab Blood Concentrations by Leading Dose and Time Point
Timepoint [8] 0 0
Cycle 3, Day 1

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/06/2015
Sample size
Target
Accrual to date
Final
569
Recruitment in Australia
Recruitment state(s)
NSW,QLD,TAS,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Kogarah
Recruitment hospital [2] 0 0
Novartis Investigative Site - St. Leonards
Recruitment hospital [3] 0 0
Novartis Investigative Site - South Brisbane
Recruitment hospital [4] 0 0
Novartis Investigative Site - Southport
Recruitment hospital [5] 0 0
Novartis Investigative Site - Hobart
Recruitment hospital [6] 0 0
Novartis Investigative Site - East Bentleigh
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
2065 - St. Leonards
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
4215 - Southport
Recruitment postcode(s) [5] 0 0
7000 - Hobart
Recruitment postcode(s) [6] 0 0
3165 - East Bentleigh
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Kansas
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
State/province [10] 0 0
Minnesota
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
Nebraska
Country [13] 0 0
United States of America
State/province [13] 0 0
Nevada
Country [14] 0 0
United States of America
State/province [14] 0 0
New Jersey
Country [15] 0 0
United States of America
State/province [15] 0 0
New York
Country [16] 0 0
United States of America
State/province [16] 0 0
North Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Oregon
Country [18] 0 0
United States of America
State/province [18] 0 0
Pennsylvania
Country [19] 0 0
United States of America
State/province [19] 0 0
Tennessee
Country [20] 0 0
United States of America
State/province [20] 0 0
Texas
Country [21] 0 0
United States of America
State/province [21] 0 0
Utah
Country [22] 0 0
United States of America
State/province [22] 0 0
Virginia
Country [23] 0 0
United States of America
State/province [23] 0 0
Washington
Country [24] 0 0
United States of America
State/province [24] 0 0
Wisconsin
Country [25] 0 0
Argentina
State/province [25] 0 0
Buenos Aires
Country [26] 0 0
Argentina
State/province [26] 0 0
Misiones
Country [27] 0 0
Argentina
State/province [27] 0 0
Sante Fe
Country [28] 0 0
Argentina
State/province [28] 0 0
Viedma
Country [29] 0 0
Argentina
State/province [29] 0 0
Cordoba
Country [30] 0 0
Argentina
State/province [30] 0 0
Tucuman
Country [31] 0 0
Belgium
State/province [31] 0 0
Brussel
Country [32] 0 0
Belgium
State/province [32] 0 0
Bruxelles
Country [33] 0 0
Belgium
State/province [33] 0 0
Liège
Country [34] 0 0
Belgium
State/province [34] 0 0
Namur
Country [35] 0 0
Belgium
State/province [35] 0 0
Sint-Niklaas
Country [36] 0 0
China
State/province [36] 0 0
Shanghai
Country [37] 0 0
China
State/province [37] 0 0
Zhejiang
Country [38] 0 0
China
State/province [38] 0 0
Beijing
Country [39] 0 0
China
State/province [39] 0 0
Guangzhou
Country [40] 0 0
Czech Republic
State/province [40] 0 0
Novy Jicin
Country [41] 0 0
Czech Republic
State/province [41] 0 0
Olomouc
Country [42] 0 0
Czech Republic
State/province [42] 0 0
Prague 5
Country [43] 0 0
France
State/province [43] 0 0
Bayonne
Country [44] 0 0
France
State/province [44] 0 0
Besançon cedex
Country [45] 0 0
France
State/province [45] 0 0
Hyères
Country [46] 0 0
France
State/province [46] 0 0
La Chaussée St Victor
Country [47] 0 0
France
State/province [47] 0 0
La Roche sur Yon Cedex
Country [48] 0 0
France
State/province [48] 0 0
Nice Cedex 2
Country [49] 0 0
France
State/province [49] 0 0
Saint-Brieuc Cédex
Country [50] 0 0
France
State/province [50] 0 0
Villejuif Cedex
Country [51] 0 0
Germany
State/province [51] 0 0
Berlin
Country [52] 0 0
Germany
State/province [52] 0 0
Frankfurt
Country [53] 0 0
Germany
State/province [53] 0 0
Gerlingen
Country [54] 0 0
Germany
State/province [54] 0 0
Halle/Saale
Country [55] 0 0
Germany
State/province [55] 0 0
Hamburg
Country [56] 0 0
Germany
State/province [56] 0 0
Homburg
Country [57] 0 0
Germany
State/province [57] 0 0
Kiel
Country [58] 0 0
Germany
State/province [58] 0 0
Magdeburg
Country [59] 0 0
Germany
State/province [59] 0 0
Mainz
Country [60] 0 0
Germany
State/province [60] 0 0
Minden
Country [61] 0 0
Germany
State/province [61] 0 0
München
Country [62] 0 0
Germany
State/province [62] 0 0
Recklinghausen
Country [63] 0 0
Germany
State/province [63] 0 0
Velbert
Country [64] 0 0
Greece
State/province [64] 0 0
GR
Country [65] 0 0
Greece
State/province [65] 0 0
Athens
Country [66] 0 0
Greece
State/province [66] 0 0
Heraklion Crete
Country [67] 0 0
Hungary
State/province [67] 0 0
Budapest
Country [68] 0 0
Hungary
State/province [68] 0 0
Debrecen
Country [69] 0 0
Hungary
State/province [69] 0 0
Gyor
Country [70] 0 0
Israel
State/province [70] 0 0
Jerusalem
Country [71] 0 0
Israel
State/province [71] 0 0
Petach Tikva
Country [72] 0 0
Israel
State/province [72] 0 0
Ramat Gan
Country [73] 0 0
Israel
State/province [73] 0 0
Tel Aviv
Country [74] 0 0
Italy
State/province [74] 0 0
CT
Country [75] 0 0
Italy
State/province [75] 0 0
MI
Country [76] 0 0
Italy
State/province [76] 0 0
PV
Country [77] 0 0
Italy
State/province [77] 0 0
SO
Country [78] 0 0
Japan
State/province [78] 0 0
Aichi
Country [79] 0 0
Japan
State/province [79] 0 0
Chiba
Country [80] 0 0
Japan
State/province [80] 0 0
Gunma
Country [81] 0 0
Japan
State/province [81] 0 0
Hokkaido
Country [82] 0 0
Japan
State/province [82] 0 0
Kanagawa
Country [83] 0 0
Japan
State/province [83] 0 0
Kumamoto
Country [84] 0 0
Japan
State/province [84] 0 0
Kyoto
Country [85] 0 0
Japan
State/province [85] 0 0
Osaka
Country [86] 0 0
Japan
State/province [86] 0 0
Tokyo
Country [87] 0 0
Japan
State/province [87] 0 0
Fukuoka
Country [88] 0 0
Mexico
State/province [88] 0 0
Distrito Federal
Country [89] 0 0
Mexico
State/province [89] 0 0
Guanajuato
Country [90] 0 0
Poland
State/province [90] 0 0
Lublin
Country [91] 0 0
Poland
State/province [91] 0 0
Warszawa
Country [92] 0 0
Singapore
State/province [92] 0 0
Singapore
Country [93] 0 0
Slovakia
State/province [93] 0 0
Bratislava
Country [94] 0 0
Slovakia
State/province [94] 0 0
Kosice
Country [95] 0 0
Spain
State/province [95] 0 0
Andalucia
Country [96] 0 0
Spain
State/province [96] 0 0
Barcelona
Country [97] 0 0
Spain
State/province [97] 0 0
Catalunya
Country [98] 0 0
Spain
State/province [98] 0 0
Comunidad Valenciana
Country [99] 0 0
Spain
State/province [99] 0 0
Galicia
Country [100] 0 0
Spain
State/province [100] 0 0
Madrid
Country [101] 0 0
Spain
State/province [101] 0 0
Santa Cruz de Tenerife
Country [102] 0 0
Spain
State/province [102] 0 0
Zaragoza
Country [103] 0 0
Thailand
State/province [103] 0 0
Bangkok
Country [104] 0 0
Thailand
State/province [104] 0 0
Songkla
Country [105] 0 0
Turkey
State/province [105] 0 0
Ankara
Country [106] 0 0
Turkey
State/province [106] 0 0
Fatih / Istanbul
Country [107] 0 0
Turkey
State/province [107] 0 0
Izmir
Country [108] 0 0
United Kingdom
State/province [108] 0 0
Cornwall
Country [109] 0 0
United Kingdom
State/province [109] 0 0
England
Country [110] 0 0
United Kingdom
State/province [110] 0 0
Bournemouth
Country [111] 0 0
United Kingdom
State/province [111] 0 0
Leeds
Country [112] 0 0
United Kingdom
State/province [112] 0 0
London
Country [113] 0 0
United Kingdom
State/province [113] 0 0
Manchester
Country [114] 0 0
United Kingdom
State/province [114] 0 0
Plymouth

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/study/NCT01007942
Trial related presentations / publications
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.
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01007942