We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01007942
First Posted: November 4, 2009
Last Update Posted: April 5, 2017
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 evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
Results First Submitted: June 10, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions: HER2/Neu Over-expressing Locally Advanced Breast Cancer
Metastatic Breast Cancer
Interventions: Drug: everolimus
Drug: Placebo
Drug: vinorelbine
Drug: trastuzumab

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
DCO ( Data cut-off) for patient disposition is 1-Apr-2015. Each Cycle = 21 days

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
284 patients randomized to the Everolimus + trastuzumab + vinorelbine arm, 280 took drug. 285 patients randomized to the placebo + trastuzumab + vinorelbine arm, 282 too drug. A total of 569 were comprised to randomized total and 562 to safety.

Reporting Groups
  Description
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 + 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)

Participant Flow:   Overall Study
    Everolimus + Vinorelbine + Trastuzumab   Placebo + Vinorelbine + Trastuzumab
STARTED   284   285 
COMPLETED   3 [1]   7 [1] 
NOT COMPLETED   281   278 
Adverse Event                29                14 
Abnormal test procedure                0                1 
Disease progression                217                242 
New cancer therapy                5                1 
Protocol Violation                1                1 
Withdrawal by Subject                19                14 
Lost to Follow-up                1                0 
Administrative problems                2                0 
Death                3                2 
Patients untreated                4                3 
[1] Pts completed= on treatment at time of DCO. Not Completed = ended treatment as per protocol.



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) consisted of all randomized patients.

Reporting Groups
  Description
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 + 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)
Total Total of all reporting groups

Baseline Measures
   Everolimus + Vinorelbine + Trastuzumab   Placebo + Vinorelbine + Trastuzumab   Total 
Overall Participants Analyzed 
[Units: Participants]
 284   285   569 
Age 
[Units: Years]
Mean (Standard Deviation)
 54.3  (10.98)   53.4  (11.00)   53.8  (10.99) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      284 100.0%      285 100.0%      569 100.0% 
Male      0   0.0%      0   0.0%      0   0.0% 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Progressive-free Survival (PFS) Per Investigator Assessment   [ Time Frame: Every 6 weeks until disease progression or death which ever occurred first up to about 41 months ]

2.  Secondary:   Overall Survival (OS)   [ Time Frame: Every 3 months until death up to 41 months ]

3.  Secondary:   Overall Response Rate (ORR)   [ Time Frame: Every 6 weeks until disease progression or death which ever occurred first up to about 41 months ]

4.  Secondary:   Clinical Benefit Rate (CBR)   [ Time Frame: Every 6 weeks until disease progression or death which ever occurred first up to about 41 months ]

5.  Secondary:   Median Time to Deterioration of the ECOG Performance Status Score   [ Time Frame: baseline, until disease progression or death up to about 41 months ]

6.  Secondary:   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%)   [ Time Frame: Baseline, until disease progression or death up to about 41 months ]

7.  Secondary:   Everolimus Blood Concentrations by Leading Dose and Time Point   [ Time Frame: Cycle 2, Day 1 ]

8.  Secondary:   Vinorelbine Blood Concentrations by Leading Dose and Time Point   [ Time Frame: Cycle 2, Day 1 ]

9.  Secondary:   Trastuzumab Blood Concentrations by Leading Dose and Time Point   [ Time Frame: Cycle 3, Day 1 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
All randomized patients were included in the FAS. Seven patients (4 in the everolimus arm & 3 in the placebo arm) were randomized but never received treatment & were therefore excluded from the Safety Set.


  More Information
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862-778-8300
e-mail: trialandresults.registries@novartis.com


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 ( EudraCT Number )
First Submitted: November 2, 2009
First Posted: November 4, 2009
Results First Submitted: June 10, 2016
Results First Posted: April 5, 2017
Last Update Posted: April 5, 2017