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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;   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 
Overall Participants Analyzed 
[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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