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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01783444




Registration number
NCT01783444
Ethics application status
Date submitted
11/01/2013
Date registered
5/02/2013
Date last updated
26/02/2021

Titles & IDs
Public title
A Phase II Study of Everolimus in Combination With Exemestane Versus Everolimus Alone Versus Capecitabine in Advance Breast Cancer.
Scientific title
A Three-arm, Randomized, Open Label, Phase II Study of Everolimus in Combination With Exemestane Versus Everolimus Alone Versus Capecitabine in the Treatment of Postmenopausal Women With Estrogen Receptor Positive, Locally Advanced, Recurrent, or Metastatic Breast Cancer After Recurrence or Progression on Prior Letrozole or Anastrozole.
Secondary ID [1] 0 0
2012-003757-28
Secondary ID [2] 0 0
CRAD001Y2201
Universal Trial Number (UTN)
Trial acronym
BOLERO-6
Linked study record

Health condition
Health condition(s) or problem(s) studied:
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 - Capecitabine
Treatment: Drugs - Exemestane
Treatment: Drugs - Everolimus

Experimental: Capecitabine 1250 mg/m2 - Capecitabine (1250 mg/m2 twice daily) for two weeks, followed by one week rest period in 3-weeks cycles (investigational arm).

Experimental: Everolimus 10 mg - Everolimus (10 mg daily) (investigational arm).

Active comparator: Everolimus 10 mg + Exemestane 25 mg - Everolimus (10 mg daily) with Exemestane (25 mg daily) (control arm).


Treatment: Drugs: Capecitabine
Capecitabine, tablets for oral use, 1250 mg/m² twice daily for 2 weeks followed by one week rest (3-week-cycle) (locally supplied)

Treatment: Drugs: Exemestane
Exemestane, tablets for oral use, 25 mg per day in (locally supplied)

Treatment: Drugs: Everolimus
Everolimus, 5 mg tablets for oral use, 10 mg (2 x 5 mg) per day (centrally supplied)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS) - Everolimus Plus Exemestane Versus Everolimus Alone
Timepoint [1] 0 0
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 39 months
Secondary outcome [1] 0 0
Progression Free Survival (PFS) - Everolimus Plus Exemestane Versus Capecitabine Alone
Timepoint [1] 0 0
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 39 months
Secondary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
Every 3 months following end of treatment visit, assessed for approximately 54 months
Secondary outcome [3] 0 0
Overall Response Rate (ORR)
Timepoint [3] 0 0
From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 43 months
Secondary outcome [4] 0 0
Clinical Benefit Rate (CBR)
Timepoint [4] 0 0
From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 43 months
Secondary outcome [5] 0 0
Time to Eastern Cooperative Oncology Group (ECOG) Performance Deterioration
Timepoint [5] 0 0
Baseline, every 6 weeks up to about 43 months
Secondary outcome [6] 0 0
Time to 10% Definitive Deterioration in the Global Health Status / Quality of Life
Timepoint [6] 0 0
Baseline, every 6 weeks up to about 43 months
Secondary outcome [7] 0 0
Mean Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Between Week 3 and 12
Timepoint [7] 0 0
Week 3, Week 12

Eligibility
Key inclusion criteria
Key

- Women with locally advanced, recurrent, or metastatic breast cancer along with confirmation of estrogen-receptor positive (ER+). Measurable disease defined as at least one lesion = 10 mm by CT or MRI that can be accurately measured in at least one dimension (CT scan slice thickness = 5 mm) OR • Bone lesions: lytic or mixed (lytic + blastic) in the absence of measurable disease as defined above.

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients who received more than one chemotherapy line. Patients with only non-measurable lesions other than lytic or mixed (lytic and blastic) bone metastasis.Previous treatment with exemestane, mTOR inhibitors, PI3K inhibitors or AKT inhibitors.

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
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
26/02/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/07/2018
Sample size
Target
Accrual to date
Final
309
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Randwick
Recruitment hospital [2] 0 0
Novartis Investigative Site - Wahroonga
Recruitment hospital [3] 0 0
Novartis Investigative Site - Malvern
Recruitment hospital [4] 0 0
Novartis Investigative Site - Parkville
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
2076 - Wahroonga
Recruitment postcode(s) [3] 0 0
3144 - Malvern
Recruitment postcode(s) [4] 0 0
3050 - Parkville
Recruitment outside Australia
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United States of America
State/province [1] 0 0
California
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Florida
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Massachusetts
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Montana
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New Jersey
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Ohio
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Oklahoma
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Tennessee
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Texas
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Virginia
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Washington
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Argentina
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Buenos Aires
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Argentina
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Misiones
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Santa Fe
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Viedma
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Cordoba
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Belgium
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Liege
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Brazil
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BA
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Brazil
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RN
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Aarhus
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Copenhagen
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Næstved
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Odense C
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Roskilde
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Vejle
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Debrecen
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Tatabanya
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India
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Andhra Pradesh
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India
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Mumbai
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Co Limerick
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Dublin 4
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Ashrafieh
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Beirut
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Hazmieh
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Saida
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Malaysia
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Sabah
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Malaysia
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Kuala Lumpur
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Peru
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Lima
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Peru
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Russian Federation
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Eskilstuna
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Joenkoeping
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Stockholm
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Uppsala
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Vasteras
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Vaxjo
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Hat Yai
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Lopburi
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Muang
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Adana
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Istanbul
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Turkey
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Izmir
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United Kingdom
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East Kilbride
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United Kingdom
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Middlesborough
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United Kingdom
State/province [67] 0 0
Nottingham

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

Ethics approval
Ethics application status

Summary
Brief summary
This was a three-arm, randomized, open label, multi-center phase II study investigating the combination of everolimus (10mg daily) with exemestane (25mg daily) versus everolimus (10mg daily) versus capecitabine (1250mg/m2 twice daily for 14 days, 3-week cycle) in patients with estrogen-receptor positive, HER2 negative, advanced breast cancer after recurrence or progression on letrozole or anastrozole.
Trial website
https://clinicaltrials.gov/study/NCT01783444
Trial related presentations / publications
Jerusalem G, de Boer RH, Hurvitz S, Yardley DA, Kovalenko E, Ejlertsen B, Blau S, Ozguroglu M, Landherr L, Ewertz M, Taran T, Fan J, Noel-Baron F, Louveau AL, Burris H. Everolimus Plus Exemestane vs Everolimus or Capecitabine Monotherapy for Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer: The BOLERO-6 Randomized Clinical Trial. JAMA Oncol. 2018 Oct 1;4(10):1367-1374. doi: 10.1001/jamaoncol.2018.2262.
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/NCT01783444