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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, Inc.
International Drug Development Institute
Information provided by (Responsible Party):
NSABP Foundation Inc
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


  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 
Overall Participants Analyzed 
[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 reported.   Anticipated Reporting 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 reported.   Anticipated Reporting 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 reported.   Anticipated Reporting 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 reported.   Anticipated Reporting 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 reported.   Anticipated Reporting 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 reported.   Anticipated Reporting 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 reported.   Anticipated Reporting 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 (100.00%)   29/29 (100.00%) 
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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