Therapy With Bevacizumab (BEV), Epirubicin, and Cyclophosphamide Followed by Docetaxel Plus Trastuzumab and BEV Given as Neoadjuvant or Adjuvant Therapy for Women With Locally Advanced HER2 Positive Invasive Breast Cancer

This study has been completed.
Sponsor:
Collaborators:
Genentech
IDDI
Information provided by (Responsible Party):
National Surgical Adjuvant Breast and Bowel Project (NSABP)
ClinicalTrials.gov Identifier:
NCT00464646
First received: April 19, 2007
Last updated: July 17, 2014
Last verified: July 2014
Results First Received: August 24, 2012  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Breast Cancer
Interventions: Drug: Epirubicin
Drug: Cyclophosphamide
Drug: Docetaxel
Drug: Trastuzumab
Drug: Bevacizumab

  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
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
Cohort A • Cohort A: Women with unresected locally advanced breast cancer (clinical Stage IIIA, IIIB, and IIIC)
Cohort B • Cohort B: Women with resected pN2 or pN3 (pathologic Stage III) breast cancer

Participant Flow:   Overall Study
    Cohort A     Cohort B  
STARTED     76     29  
COMPLETED     76     29  
NOT COMPLETED     0     0  



  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.
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Reporting Groups
  Description
Cohort A • Cohort A: Women with unresected locally advanced breast cancer (clinical Stage IIIA, IIIB, and IIIC)
Cohort B • Cohort B: Women with resected pN2 or pN3 (pathologic Stage III) breast cancer
Total Total of all reporting groups

Baseline Measures
    Cohort A     Cohort B     Total  
Number of Participants  
[units: participants]
  76     29     105  
Age  
[units: years]
Mean ± Standard Deviation
  48.1  ± 9.6     53.8  ± 11.4     49.7  ± 10.4  
Age, Customized  
[units: participants]
     
18 to less than 50 years     39     10     49  
>=50 years and <=59 years     27     8     35  
> 59 years     10     11     21  
Gender  
[units: participants]
     
Female     76     29     105  
Male     0     0     0  
Race/Ethnicity, Customized  
[units: participants]
     
White     65     26     91  
Black or African American     10     3     13  
Native Hawaiian or other Pacific Islander     0     0     0  
American Indian or Alaskan Native     0     0     0  
Asian     1     0     1  
Unknown     0     0     0  
Race/Ethnicity, Customized  
[units: participants]
     
Hispanic or Latino     2     0     2  
Not Hispanic or Latino     70     29     99  
Unknown     4     0     4  



  Outcome Measures

1.  Primary:   Number of Patients With Pathological Complete Response (pCR) in the Breast and Nodes for Patients With HER2-positive LABC Following Neoadjuvant Treatment (Cohort A)   [ Time Frame: Assessed at time of surgery on average at 8 months ]

2.  Primary:   Cardiac Event Rate as Determined by LVEF Assessment   [ Time Frame: Cohort A: Baseline, post-treatment with EC, 2-4 weeks after surgery, and 9, 12, 15, and 18 months from study entry. Cohort B: Baseline, post-treatment with EC, 2-3 weeks after the last dose of docetaxel, and 6, 9, 12, 15, and 18 months from study entry. ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   Yes

3.  Secondary:   pCR in the Breast (Cohort A)   [ Time Frame: Assessed at the time of surgery ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

4.  Secondary:   Clinical Complete Response (cCR)   [ Time Frame: Determined at baseline, between EC and docetaxel, and following docetaxel (before surgery) ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

5.  Secondary:   Grade 3 and 4 Toxicities, Including Toxicities Associated With Radiation Therapy(RT)   [ Time Frame: Before each cycle of pre-op Rx; 2-4 wks after the last docetaxel dose; 2-4 wks post surgery (Cohort A); every 6 wks during post-op Rx (Cohort A); every 6 wks during targeted therapy alone (Cohort B); RT complications assessed at 12 mos from study entry ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   Yes

6.  Secondary:   Recurrence-free Survival   [ Time Frame: From the first dose of study therapy until the date of recurrence or for a maximum of five (5) years from study entry ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

7.  Secondary:   Overall Survival   [ Time Frame: From the first dose of study therapy until the date of death or for a maximum of five (5) years from study entry ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

8.  Secondary:   Percentage of Surgical Complications (From Mastectomy, Lumpectomy, and Axillary Staging Procedures) (Cohort A)   [ Time Frame: 2-4 weeks after surgery and at 9 and 12 months from study entry ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   Yes


  Serious Adverse Events


  Other Adverse Events
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Time Frame 5 years
Additional Description No text entered.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

Reporting Groups
  Description
Cohort A • Cohort A: Women with unresected locally advanced breast cancer (clinical Stage IIIA, IIIB, and IIIC)
Cohort B • Cohort B: Women with resected pN2 or pN3 (pathologic Stage III) breast cancer

Other Adverse Events
    Cohort A     Cohort B  
Total, other (not including serious) adverse events      
# participants affected / at risk     76/76     29/29  
Blood and lymphatic system disorders      
Neutrophils    
# participants affected / at risk     19/76 (25.00%)     5/29 (17.24%)  
Leucocytes    
# participants affected / at risk     17/76 (22.37%)     3/29 (10.34%)  
Hemoglobin    
# participants affected / at risk     10/76 (13.16%)     7/29 (24.14%)  
Lymphopenia    
# participants affected / at risk     12/76 (15.79%)     7/29 (24.14%)  
Blood - Other (low HCT)    
# participants affected / at risk     4/76 (5.26%)     0/29 (0.00%)  
Cardiac disorders      
Hypertension    
# participants affected / at risk     29/76 (38.16%)     12/29 (41.38%)  
Left ventricular systolic function    
# participants affected / at risk     13/76 (17.11%)     3/29 (10.34%)  
Ear and labyrinth disorders      
Tinnitus    
# participants affected / at risk     5/76 (6.58%)     1/29 (3.45%)  
Eye disorders      
Watery eye    
# participants affected / at risk     5/76 (6.58%)     6/29 (20.69%)  
Blurred vision    
# participants affected / at risk     2/76 (2.63%)     3/29 (10.34%)  
Gastrointestinal disorders      
Mucositis (functional/symptomatic) - oral cavity    
# participants affected / at risk     31/76 (40.79%)     8/29 (27.59%)  
Vomiting    
# participants affected / at risk     24/76 (31.58%)     7/29 (24.14%)  
Diarrhea    
# participants affected / at risk     17/76 (22.37%)     6/29 (20.69%)  
Dehydration    
# participants affected / at risk     15/76 (19.74%)     7/29 (24.14%)  
Constipation    
# participants affected / at risk     10/76 (13.16%)     1/29 (3.45%)  
Heartburn    
# participants affected / at risk     9/76 (11.84%)     2/29 (6.90%)  
Mucositis (clinical exam) - oral cavity    
# participants affected / at risk     14/76 (18.42%)     5/29 (17.24%)  
Taste alteration    
# participants affected / at risk     12/76 (15.79%)     4/29 (13.79%)  
Gastritis    
# participants affected / at risk     6/76 (7.89%)     0/29 (0.00%)  
Esophagitis    
# participants affected / at risk     4/76 (5.26%)     1/29 (3.45%)  
Hemorhoids    
# participants affected / at risk     1/76 (1.32%)     5/29 (17.24%)  
General disorders      
Pain - muscle    
# participants affected / at risk     28/76 (36.84%)     11/29 (37.93%)  
Pain - bone    
# participants affected / at risk     25/76 (32.89%)     14/29 (48.28%)  
Pain - joint    
# participants affected / at risk     19/76 (25.00%)     12/29 (41.38%)  
Pain - head/headache    
# participants affected / at risk     19/76 (25.00%)     6/29 (20.69%)  
Pain - extremity - limb    
# participants affected / at risk     16/76 (21.05%)     4/29 (13.79%)  
Pain - chest/thorax    
# participants affected / at risk     11/76 (14.47%)     2/29 (6.90%)  
Pain - breast    
# participants affected / at risk     9/76 (11.84%)     1/29 (3.45%)  
Pain - back    
# participants affected / at risk     8/76 (10.53%)     6/29 (20.69%)  
Pain - abdominal NOS    
# participants affected / at risk     8/76 (10.53%)     2/29 (6.90%)  
Pain - pain NOS    
# participants affected / at risk     5/76 (6.58%)     6/29 (20.69%)  
Nausea    
# participants affected / at risk     23/76 (30.26%)     12/29 (41.38%)  
Fatigue    
# participants affected / at risk     47/76 (61.84%)     20/29 (68.97%)  
Fever    
# participants affected / at risk     4/76 (5.26%)     1/29 (3.45%)  
Hot flashes    
# participants affected / at risk     15/76 (19.74%)     4/29 (13.79%)  
Anorexia    
# participants affected / at risk     12/76 (15.79%)     5/29 (17.24%)  
Insomnia    
# participants affected / at risk     10/76 (13.16%)     3/29 (10.34%)  
Edema - limb    
# participants affected / at risk     6/76 (7.89%)     1/29 (3.45%)  
Weight loss    
# participants affected / at risk     5/76 (6.58%)     3/29 (10.34%)  
Infections and infestations      
Infection with normal ANC - skin (cellulites)    
# participants affected / at risk     11/76 (14.47%)     1/29 (3.45%)  
Infection with normal ANC - bladder (urinary)    
# participants affected / at risk     6/76 (7.89%)     6/29 (20.69%)  
Febrile neutropenia    
# participants affected / at risk     4/76 (5.26%)     3/29 (10.34%)  
Infection with normal ANC - sinus    
# participants affected / at risk     5/76 (6.58%)     0/29 (0.00%)  
Infection with unknown ANC - sinus    
# participants affected / at risk     5/76 (6.58%)     0/29 (0.00%)  
Infection with unknown ANC - upper airway NOS    
# participants affected / at risk     5/76 (6.58%)     0/29 (0.00%)  
Infection with normal ANC - upper airway NOS    
# participants affected / at risk     3/76 (3.95%)     2/29 (6.90%)  
Infection with unknown ANC - bronchus    
# participants affected / at risk     3/76 (3.95%)     2/29 (6.90%)  
Infection - other- shingles    
# participants affected / at risk     1/76 (1.32%)     2/29 (6.90%)  
Investigations      
Hyperglycemia    
# participants affected / at risk     5/76 (6.58%)     1/29 (3.45%)  
Metabolism and nutrition disorders      
ALT    
# participants affected / at risk     4/76 (5.26%)     1/29 (3.45%)  
AST, SGOT    
# participants affected / at risk     4/76 (5.26%)     1/29 (3.45%)  
Hyponatremia    
# participants affected / at risk     2/76 (2.63%)     2/29 (6.90%)  
Nervous system disorders      
Neuropathy - sensory    
# participants affected / at risk     18/76 (23.68%)     8/29 (27.59%)  
Dizziness    
# participants affected / at risk     6/76 (7.89%)     1/29 (3.45%)  
Neuropathy - motor    
# participants affected / at risk     5/76 (6.58%)     1/29 (3.45%)  
Psychiatric disorders      
Mood alteration - depression    
# participants affected / at risk     11/76 (14.47%)     5/29 (17.24%)  
Mood alteration - anxiety    
# participants affected / at risk     9/76 (11.84%)     1/29 (3.45%)  
Reproductive system and breast disorders      
Vaginitis    
# participants affected / at risk     2/76 (2.63%)     2/29 (6.90%)  
Respiratory, thoracic and mediastinal disorders      
Cough    
# participants affected / at risk     9/76 (11.84%)     3/29 (10.34%)  
Dyspnea    
# participants affected / at risk     5/76 (6.58%)     1/29 (3.45%)  
Rhinitis    
# participants affected / at risk     9/76 (11.84%)     2/29 (6.90%)  
Skin and subcutaneous tissue disorders      
Alopecia    
# participants affected / at risk     65/76 (85.53%)     24/29 (82.76%)  
Rash    
# participants affected / at risk     13/76 (17.11%)     9/29 (31.03%)  
Hand - foot    
# participants affected / at risk     9/76 (11.84%)     2/29 (6.90%)  
Nail Changes    
# participants affected / at risk     16/76 (21.05%)     9/29 (31.03%)  
Pruritus    
# participants affected / at risk     4/76 (5.26%)     1/29 (3.45%)  
Events were collected by systematic assessment



  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
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  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 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.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Diana Gosik
Organization: NSABP Foundation, Inc.
phone: 412-339-5333
e-mail: diana.gosik@nsabp.org


No publications provided


Responsible Party: National Surgical Adjuvant Breast and Bowel Project (NSABP)
ClinicalTrials.gov Identifier: NCT00464646     History of Changes
Other Study ID Numbers: NSABP FB-5
Study First Received: April 19, 2007
Results First Received: August 24, 2012
Last Updated: July 17, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Canada: Health Canada
Canada: Ethics Review Committee