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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00863655




Registration number
NCT00863655
Ethics application status
Date submitted
16/03/2009
Date registered
18/03/2009
Date last updated
2/05/2017

Titles & IDs
Public title
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
Scientific title
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
Secondary ID [1] 0 0
2008-008698-69
Secondary ID [2] 0 0
CRAD001Y2301
Universal Trial Number (UTN)
Trial acronym
BOLERO-2
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 - Everolimus
Treatment: Drugs - Exemestane
Treatment: Drugs - Everolimus Placebo

Experimental: Everolimus + Exemestane - Everolimus 10 mg daily in combination with exemestane 25 mg daily

Active comparator: Placebo + Exemestane - Placebo of everolimus in combination with exemestane 25 mg daily


Treatment: Drugs: 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.

Treatment: Drugs: Exemestane
Exemestane 25 mg orally daily.

Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS) Based on Local Radiology Review of Tumor Assessments.
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 about 19 months
Secondary outcome [1] 0 0
Overall Survival (OS) by Number of Deaths
Timepoint [1] 0 0
up to 53 months
Secondary outcome [2] 0 0
Overall Survival (OS) by Median
Timepoint [2] 0 0
up to 53 months
Secondary outcome [3] 0 0
Overall Response Rate (ORR)
Timepoint [3] 0 0
up to 21 months
Secondary outcome [4] 0 0
Clinical Benefit Rate (CBR)
Timepoint [4] 0 0
up to 21 months
Secondary outcome [5] 0 0
Proportion of Patients With no Deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG PS) Using Kaplan-Meier
Timepoint [5] 0 0
2, 4, 6, 9 months
Secondary outcome [6] 0 0
Patient-reported Outcomes (PROs): Time to Deterioration of PRO Scores Using Kaplan Meier - EORTC QLQ-C30
Timepoint [6] 0 0
Up to 21 months
Secondary outcome [7] 0 0
Proportion of Patients With Having no Overall Response Based on Investigator Assessment
Timepoint [7] 0 0
2, 4, 6, 9 months
Secondary outcome [8] 0 0
Duration of Response (Among Participants With Best Overall Response of CR or PR) Estimated Per Kaplan-Meier
Timepoint [8] 0 0
21 months
Secondary outcome [9] 0 0
Everolimus Concentrations at Week 4
Timepoint [9] 0 0
pre-dose, 2 hours post-dose
Secondary outcome [10] 0 0
Exemestane Concentrations at Week 4
Timepoint [10] 0 0
predose, 2 hours post-dose
Secondary outcome [11] 0 0
Estradiol Plasma Concentrations
Timepoint [11] 0 0
Baseline, Week 4

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key 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 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 administering the treatment/s
The people assessing the outcomes
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
3/06/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
4/12/2014
Sample size
Target
Accrual to date
Final
724
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Nambour
Recruitment hospital [2] 0 0
Novartis Investigative Site - Redcliffe
Recruitment hospital [3] 0 0
Novartis Investigative Site - Bedford Park
Recruitment hospital [4] 0 0
Novartis Investigative Site - Parkville
Recruitment hospital [5] 0 0
Novartis Investigative Site - Subiaco
Recruitment postcode(s) [1] 0 0
4560 - Nambour
Recruitment postcode(s) [2] 0 0
4020 - Redcliffe
Recruitment postcode(s) [3] 0 0
5042 - Bedford Park
Recruitment postcode(s) [4] 0 0
3002 - Parkville
Recruitment postcode(s) [5] 0 0
3050 - Parkville
Recruitment postcode(s) [6] 0 0
6008 - Subiaco
Recruitment outside Australia
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United States of America
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Arizona
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Indiana
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Wisconsin
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Austria
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Innsbruck
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Linz
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Salzburg
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France
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Galicia
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Chiang Mai
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Ankara
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Izmir
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Chelmsford
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Sheffield
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Southampton

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT00863655