Efficacy and Safety of Everolimus in Combination Therapy, in Patients With HER2-overexpressing Metastatic Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00426556
First received: January 23, 2007
Last updated: April 2, 2015
Last verified: April 2015
Results First Received: March 20, 2015  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Metastatic Breast Cancer
Interventions: Drug: Everolimus
Drug: Trastuzumab
Drug: Paclitaxel

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Based on the results of the Phase I portion of this study, in addition to all available information on daily and weekly everolimus regimen in breast cancer and other tumors, all patients in the Phase II portion of the study were allocated to one arm to receive the recommended everolimus dose of 10 mg daily in combination with PT.

Reporting Groups
  Description
Phase I - RAD001 5mg + PT, Daily Daily dosing schedule of Everolimus 5mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab
Phase I - RAD001 10mg + PT, Daily Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab
Phase I - RAD001 30mg + PT, Weekly Weekly dosing schedule of Everolimus 30mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab.
Phase II - RAD001 10mg + PT, Daily Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab

Participant Flow for 4 periods

Period 1:   Phase I - Core Phase
    Phase I - RAD001 5mg + PT, Daily     Phase I - RAD001 10mg + PT, Daily     Phase I - RAD001 30mg + PT, Weekly     Phase II - RAD001 10mg + PT, Daily  
STARTED     6     17     10     0  
COMPLETED     5     7     7     0  
NOT COMPLETED     1     10     3     0  
Disease Progression                 0                 6                 2                 0  
Adverse Event                 1                 3                 1                 0  
Death                 0                 1                 0                 0  

Period 2:   Phase I - Extension Phase
    Phase I - RAD001 5mg + PT, Daily     Phase I - RAD001 10mg + PT, Daily     Phase I - RAD001 30mg + PT, Weekly     Phase II - RAD001 10mg + PT, Daily  
STARTED     5     7     7     0  
COMPLETED     0     1     0     0  
NOT COMPLETED     5     6     7     0  
Adverse Event                 0                 1                 1                 0  
Disease Progression                 5                 5                 6                 0  

Period 3:   Phase II - Core Phase
    Phase I - RAD001 5mg + PT, Daily     Phase I - RAD001 10mg + PT, Daily     Phase I - RAD001 30mg + PT, Weekly     Phase II - RAD001 10mg + PT, Daily  
STARTED     0     0     0     55  
COMPLETED     0     0     0     28  
NOT COMPLETED     0     0     0     27  
Withdrawal by Subject                 0                 0                 0                 3  
Disease Progression                 0                 0                 0                 16  
Adverse Event                 0                 0                 0                 8  

Period 4:   Phase II - Extension Phase
    Phase I - RAD001 5mg + PT, Daily     Phase I - RAD001 10mg + PT, Daily     Phase I - RAD001 30mg + PT, Weekly     Phase II - RAD001 10mg + PT, Daily  
STARTED     0     0     0     24 [1]
COMPLETED     0     0     0     1 [2]
NOT COMPLETED     0     0     0     23  
Disease Progression                 0                 0                 0                 21  
Adverse Event                 0                 0                 0                 2  
[1] 4 patients did not enter the Extension phase.
[2] Completed means 'Ongoing'



  Baseline Characteristics
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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 patients who received a least one dose of any one compound of the study treatment. Patients were analyzed according to the everolimus dose level to which they enrolled.

Reporting Groups
  Description
Phase I - RAD001 5mg + PT, Daily Daily dosing schedule of Everolimus 5mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab
Phase I - RAD001 10mg + PT, Daily Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab
Phase I - RAD001 30mg + PT, Weekly Weekly dosing schedule of Everolimus 30mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab.
Phase II - RAD001 10mg + PT, Daily Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel & Trastuzumab
Total Total of all reporting groups

Baseline Measures
    Phase I - RAD001 5mg + PT, Daily     Phase I - RAD001 10mg + PT, Daily     Phase I - RAD001 30mg + PT, Weekly     Phase II - RAD001 10mg + PT, Daily     Total  
Number of Participants  
[units: participants]
  6     17     10     55     88  
Age, Customized  
[units: Participants]
         
Phase I : < 65     6     13     6     0     25  
Phase I : >= 65     0     4     4     0     8  
Phase II : < 65     0     0     0     49     49  
Phase II : >= 65     0     0     0     6     6  
Gender, Customized  
[units: Participants]
         
Phase I- Female     6     17     10     0     33  
Phase II - Female     0     0     0     55     55  
Who Performance Status [1]
[units: Participants]
         
0     4     5     4     36     49  
1     2     12     6     19     39  
[1] 0=Fully active, able to carry out normal activity without restriction, 1=Restricted in physical strenuous activity but ambulatory and able to carry work of a light or sedentary nature e.g. light house work, office work.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Phase II: Overall Response Rate   [ Time Frame: every 8 - 9 weeks until disease progression or a new lesion is identified ]

2.  Secondary:   Phase I: Best Overall Response (BOR)   [ Time Frame: every 8 - 9 weeks until disease progression or a new lesion is identified ]

3.  Secondary:   Phase II: Progression Free Survival (PFS)   [ Time Frame: every 8 - 9 weeks until disease progression or a new lesion is identified ]

4.  Secondary:   Phase II: Overall Survival (OS)   [ Time Frame: every 3 months until death ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
No text entered.


  More Information
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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


No publications provided


Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00426556     History of Changes
Other Study ID Numbers: CRAD001J2101, 2006-001596-37
Study First Received: January 23, 2007
Results First Received: March 20, 2015
Last Updated: April 2, 2015
Health Authority: United States: Food and Drug Administration
Belgium: Federal Agency for Medicines and Health Products, FAMHP
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Netherlands: Dutch Health Care Inspectorate
Spain: Spanish Agency of Medicines