BEATRICE Study: A Study of Bevacizumab (Avastin) Adjuvant Therapy in Triple Negative Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00528567
First received: September 11, 2007
Last updated: August 5, 2015
Last verified: August 2015
Results First Received: February 28, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Breast Cancer
Interventions: Drug: Bevacizumab
Drug: Standard adjuvant chemotherapy

  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
Bevacizumab and Chemotherapy

Participants randomized to receive bevacizumab and chemotherapy.

For these patients, bevacizumab was given in combination with chemotherapy at a dose of 5 mg/kg/week equivalent using 1 of 3 different scheduling options depending on the schedule of the adjuvant chemotherapy selected. After completing chemotherapy + bevacizumab (treatment period 1), patients in this arm received bevacizumab monotherapy up to a total duration of 1 year (treatment period 2).

At the end of treatment (i.e., after approximately 55 weeks), patients were followed up until the end of the study.

Chemotherapy

Participants randomized to receive chemotherapy alone.

For patients randomized to the chemotherapy alone arm, investigators could select from one of three chemotherapy regimens. After completing chemotherapy (treatment period 1) patients entered a post-treatment surveillance period for the remainder of the first year after randomization (treatment period 2).

At the end of treatment (i.e., after approximately 55 weeks), patients were followed up until the end of the study.


Participant Flow:   Overall Study
    Bevacizumab and Chemotherapy     Chemotherapy  
STARTED     1301     1290  
Intention to Treat     1301     1290  
Safety Population     1288     1271  
COMPLETED     870     982  
NOT COMPLETED     431     308  
Death                 4                 5  
Breast Cancer Recurrence/2nd Primary                 30                 60  
Adverse Event/Intermittent Illness                 255                 29  
Violation Criteria at Entry                 3                 17  
Withdrew Consent                 59                 55  
Refused Treatment/Did Not Cooperate                 52                 42  
Failure to Return                 1                 4  
Other Protocol Violation                 5                 21  
Administrative/Other                 22                 75  



  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
Bevacizumab and Chemotherapy Participants randomized to receive bevacizumab and chemotherapy
Chemotherapy Participants randomized to receive chemotherapy alone
Total Total of all reporting groups

Baseline Measures
    Bevacizumab and Chemotherapy     Chemotherapy     Total  
Number of Participants  
[units: participants]
  1301     1290     2591  
Age, Customized  
[units: participants]
     
< 40 years     231     253     484  
>= 40 to < 65 years     952     916     1868  
>= 65 years     118     121     239  
Gender  
[units: participants]
     
Female     1301     1290     2591  
Male     0     0     0  



  Outcome Measures
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1.  Primary:   Time to Invasive Disease-free Survival (IDFS) Event   [ Time Frame: Event driven (until data cutoff: 29 February 2012: up to 49 months) ]

2.  Primary:   Percentage of Participants With Invasive Disease-free Survival (IDFS) Events   [ Time Frame: Event driven (until data cutoff: 29 February 2012 up to 49 months) ]

3.  Primary:   Time to Invasive Disease-free Survival (IDFS) Event Excluding Second Primary Non-Breast Invasive Cancer   [ Time Frame: Event driven (until data cutoff: 29 February 2012: up to 49 months) ]

4.  Primary:   Percentage of Participants With Invasive Disease-free Survival (IDFS) Events Excluding Second Primary Non-Breast Invasive Cancer   [ Time Frame: Event driven (until data cutoff: 29 February 2012: up to 49 months) ]

5.  Secondary:   Time to Overall Survival (OS) Event   [ Time Frame: Event driven (until data cutoff: 29 February 2012: up to 49 months) ]

6.  Secondary:   Time to Overall Survival (OS) Event   [ Time Frame: Event driven (until data cutoff: 30 June 2014: up to 77 months) ]

7.  Secondary:   Percentage of Participants With Overall Survival (OS) Event   [ Time Frame: Event driven (until data cut off: 29 February 2012: up to 49 months) ]

8.  Secondary:   Percentage of Participants With Overall Survival (OS) Event   [ Time Frame: Event driven (until data cut off: 30 June 2014: up to 77 months) ]

9.  Secondary:   Time to Breast Cancer-Free Interval (BCFI) Event   [ Time Frame: Event driven (until data cutoff: 29 February 2012: up to 49 months) ]

10.  Secondary:   Percentage of Participants With Breast Cancer-Free Interval (BCFI) Events   [ Time Frame: Event driven (until data cutoff: 29 February 2012: up to 49 months) ]

11.  Secondary:   Time to Disease-Free Survival (DFS) Event   [ Time Frame: Event driven (until data cutoff: 29 February 2012: up to 49 months) ]

12.  Secondary:   Percentage of Participants With Disease-Free Survival (DFS) Events   [ Time Frame: Event driven (until data cutoff: 29 February 2012: up to 49 months) ]

13.  Secondary:   Time to Distant Disease-Free Survival (DDFS) Event   [ Time Frame: Event driven (until data cutoff: 29 February 2012: up to 49 months) ]

14.  Secondary:   Percentage of Participants With Distant Disease-Free Survival (DDFS) Events   [ Time Frame: Event driven (until data cutoff: 29 February 2012: up to 49 months) ]

15.  Secondary:   Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) and Deaths   [ Time Frame: Through end of study: 30 June 2014: up to 77 months ]


  Serious Adverse Events


  Other Adverse Events
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Time Frame Through end of study, 30 June 2014
Additional Description The analysis set was the safety population, defined as all randomized participants who received at least one dose of study drug. Participants who received at least one full or partial dose of bevacizumab were included in the bevacizumab and chemotherapy arm; all others, in the chemotherapy arm. MedDRA (15.0) and MedDRA (17.0) were used.

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

Reporting Groups
  Description
Bevacizumab and Chemotherapy (0-18 Months) Occurring in participants who received bevacizumab and chemotherapy, during treatment period (0-18 months) after first dose
Chemotherapy (0-18 Months) Occurring in participants who received chemotherapy alone, during treatment period (0-18 months) after first dose
Bevacizumab and Chemotherapy (>18 Months) Occurring in participants who received bevacizumab and chemotherapy, during follow-up period (>18 months) after first dose
Chemotherapy (>18 Months) Occurring in participants who received chemotherapy alone, during follow-up period (>18 months) after first dose

Other Adverse Events
    Bevacizumab and Chemotherapy (0-18 Months)     Chemotherapy (0-18 Months)     Bevacizumab and Chemotherapy (>18 Months)     Chemotherapy (>18 Months)  
Total, other (not including serious) adverse events          
# participants affected / at risk     1268/1288 (98.45%)     1233/1271 (97.01%)     0/1288 (0.00%)     0/1271 (0.00%)  
Blood and lymphatic system disorders          
Neutropenia        
# participants affected / at risk     503/1288 (39.05%)     479/1271 (37.69%)          
Leukopenia        
# participants affected / at risk     210/1288 (16.30%)     215/1271 (16.92%)          
Anaemia        
# participants affected / at risk     140/1288 (10.87%)     175/1271 (13.77%)          
Cardiac disorders          
Left ventricular dysfunction        
# participants affected / at risk     261/1288 (20.26%)     165/1271 (12.98%)          
Eye disorders          
Lacrimation increased        
# participants affected / at risk     156/1288 (12.11%)     109/1271 (8.58%)          
Gastrointestinal disorders          
Nausea        
# participants affected / at risk     881/1288 (68.40%)     880/1271 (69.24%)          
Stomatitis        
# participants affected / at risk     663/1288 (51.48%)     469/1271 (36.90%)          
Vomiting        
# participants affected / at risk     480/1288 (37.27%)     459/1271 (36.11%)          
Constipation        
# participants affected / at risk     444/1288 (34.47%)     401/1271 (31.55%)          
Diarrhoea        
# participants affected / at risk     418/1288 (32.45%)     350/1271 (27.54%)          
Dyspepsia        
# participants affected / at risk     201/1288 (15.61%)     165/1271 (12.98%)          
Abdominal pain upper        
# participants affected / at risk     138/1288 (10.71%)     112/1271 (8.81%)          
Abdominal pain        
# participants affected / at risk     123/1288 (9.55%)     124/1271 (9.76%)          
Gingival bleeding        
# participants affected / at risk     138/1288 (10.71%)     10/1271 (0.79%)          
Dry mouth        
# participants affected / at risk     61/1288 (4.74%)     76/1271 (5.98%)          
Haemorrhoids        
# participants affected / at risk     78/1288 (6.06%)     58/1271 (4.56%)          
General disorders          
Fatigue        
# participants affected / at risk     533/1288 (41.38%)     539/1271 (42.41%)          
Asthenia        
# participants affected / at risk     230/1288 (17.86%)     223/1271 (17.55%)          
Pyrexia        
# participants affected / at risk     214/1288 (16.61%)     164/1271 (12.90%)          
Oedema peripheral        
# participants affected / at risk     145/1288 (11.26%)     164/1271 (12.90%)          
Pain        
# participants affected / at risk     72/1288 (5.59%)     58/1271 (4.56%)          
Influenza like illness        
# participants affected / at risk     68/1288 (5.28%)     61/1271 (4.80%)          
Infections and infestations          
Nasopharyngitis        
# participants affected / at risk     137/1288 (10.64%)     125/1271 (9.83%)          
Upper respiratory tract infection        
# participants affected / at risk     103/1288 (8.00%)     109/1271 (8.58%)          
Urinary tract infection        
# participants affected / at risk     95/1288 (7.38%)     100/1271 (7.87%)          
Injury, poisoning and procedural complications          
Radiation skin injury        
# participants affected / at risk     151/1288 (11.72%)     190/1271 (14.95%)          
Investigations          
Ejection fraction decreased        
# participants affected / at risk     103/1288 (8.00%)     71/1271 (5.59%)          
Aspartate aminotransferase increased        
# participants affected / at risk     84/1288 (6.52%)     49/1271 (3.86%)          
Gamma-glutamyltransferase increased        
# participants affected / at risk     82/1288 (6.37%)     45/1271 (3.54%)          
Alanine aminotransferase increased        
# participants affected / at risk     67/1288 (5.20%)     50/1271 (3.93%)          
Weight decreased        
# participants affected / at risk     72/1288 (5.59%)     28/1271 (2.20%)          
Metabolism and nutrition disorders          
Decreased appetite        
# participants affected / at risk     260/1288 (20.19%)     223/1271 (17.55%)          
Musculoskeletal and connective tissue disorders          
Arthralgia        
# participants affected / at risk     414/1288 (32.14%)     252/1271 (19.83%)          
Myalgia        
# participants affected / at risk     278/1288 (21.58%)     273/1271 (21.48%)          
Pain in extremity        
# participants affected / at risk     198/1288 (15.37%)     171/1271 (13.45%)          
Back pain        
# participants affected / at risk     172/1288 (13.35%)     141/1271 (11.09%)          
Bone pain        
# participants affected / at risk     99/1288 (7.69%)     111/1271 (8.73%)          
Musculoskeletal pain        
# participants affected / at risk     162/1288 (12.58%)     123/1271 (9.68%)          
Nervous system disorders          
Headache        
# participants affected / at risk     440/1288 (34.16%)     289/1271 (22.74%)          
Dysgeusia        
# participants affected / at risk     243/1288 (18.87%)     230/1271 (18.10%)          
Neuropathy peripheral        
# participants affected / at risk     138/1288 (10.71%)     135/1271 (10.62%)          
Peripheral sensory neuropathy        
# participants affected / at risk     137/1288 (10.64%)     128/1271 (10.07%)          
Dizziness        
# participants affected / at risk     130/1288 (10.09%)     121/1271 (9.52%)          
Paraesthesia        
# participants affected / at risk     88/1288 (6.83%)     91/1271 (7.16%)          
Psychiatric disorders          
Insomnia        
# participants affected / at risk     191/1288 (14.83%)     217/1271 (17.07%)          
Anxiety        
# participants affected / at risk     88/1288 (6.83%)     78/1271 (6.14%)          
Depression        
# participants affected / at risk     57/1288 (4.43%)     69/1271 (5.43%)          
Renal and urinary disorders          
Proteinuria        
# participants affected / at risk     195/1288 (15.14%)     24/1271 (1.89%)          
Reproductive system and breast disorders          
Breast pain        
# participants affected / at risk     60/1288 (4.66%)     86/1271 (6.77%)          
Respiratory, thoracic and mediastinal disorders          
Epistaxis        
# participants affected / at risk     478/1288 (37.11%)     75/1271 (5.90%)          
Cough        
# participants affected / at risk     215/1288 (16.69%)     161/1271 (12.67%)          
Oropharyngeal pain        
# participants affected / at risk     179/1288 (13.90%)     99/1271 (7.79%)          
Dyspnoea        
# participants affected / at risk     144/1288 (11.18%)     123/1271 (9.68%)          
Rhinorrhoea        
# participants affected / at risk     104/1288 (8.07%)     65/1271 (5.11%)          
Dysphonia        
# participants affected / at risk     99/1288 (7.69%)     19/1271 (1.49%)          
Skin and subcutaneous tissue disorders          
Alopecia        
# participants affected / at risk     807/1288 (62.66%)     833/1271 (65.54%)          
Nail disorder        
# participants affected / at risk     183/1288 (14.21%)     150/1271 (11.80%)          
Rash        
# participants affected / at risk     160/1288 (12.42%)     137/1271 (10.78%)          
Erythema        
# participants affected / at risk     86/1288 (6.68%)     114/1271 (8.97%)          
Palmar-Plantar erythrodysaesthesia syndrome        
# participants affected / at risk     92/1288 (7.14%)     70/1271 (5.51%)          
Dry skin        
# participants affected / at risk     70/1288 (5.43%)     72/1271 (5.66%)          
Pruritus        
# participants affected / at risk     71/1288 (5.51%)     63/1271 (4.96%)          
Skin hyperpigmentation        
# participants affected / at risk     68/1288 (5.28%)     49/1271 (3.86%)          
Vascular disorders          
Hypertension        
# participants affected / at risk     456/1288 (35.40%)     65/1271 (5.11%)          
Hot flush        
# participants affected / at risk     206/1288 (15.99%)     208/1271 (16.37%)          
Lymphoedema        
# participants affected / at risk     70/1288 (5.43%)     74/1271 (5.82%)          
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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