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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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
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Plymouth

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.