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

Study Overview
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Brief Summary
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The main objective of the trial is to compare Invasive Disease-Free Survival (IDFS) of patients randomised to treatment with adjuvant chemotherapy alone or to adjuvant chemotherapy with 1 year of bevacizumab. The secondary objectives of this trial are to: compare Overall Survival (OS), Breast Cancer-Free Interval (BCFI), Disease- Free Survival (DFS) and Distant Disease-Free Survival (DDFS) of patients randomised to treatment with adjuvant chemotherapy alone or to adjuvant chemotherapy in combination with 1 year of bevacizumab evaluate the safety and tolerability of bevacizumab An exploratory sub-study (not reported here) was to identify biomarkers (from tumour or serum) predictive of toxicity and for the level of benefit from the addition of bevacizumab to standard adjuvant systemic treatment.

Official Title
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An International Multi-centre Open-label 2-arm Phase III Trial of Adjuvant Bevacizumab in Triple Negative Breast Cancer.

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Bevacizumab
* Drug: Standard adjuvant chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, >=18 years of age; operable primary invasive breast cancer; completed definitive loco-regional surgery; primary tumor centrally confirmed as triple negative. Exclusion Criteria: locally advanced breast cancers; previous breast cancer history; clinically significant cardiovascular disease.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bevacizumab and Chemotherapy<br>Participants randomized to receive bevacizumab in combination with chemotherapy as prescribed. | Drug: Bevacizumab<br>* Bevacizumab was administered at a dose equivalent of 5 mg/kg/week using 1 of 3 different scheduling options depending on the schedule of the adjuvant chemotherapy regimen selected for an individual patient.<br>* Other names: Avastin;Drug: Standard adjuvant chemotherapy<br>* All chemotherapy schedules and doses for each patient were prescribed according to the labeled indication of the country in which the patient was receiving therapy.<br>|
| Active Comparator: Chemotherapy<br>Participants randomized to receive standard adjuvant chemotherapy as prescribed. | Drug: Standard adjuvant chemotherapy<br>* All chemotherapy schedules and doses for each patient were prescribed according to the labeled indication of the country in which the patient was receiving therapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Invasive Disease-free Survival (IDFS) Event | IDFS, was a composite endpoint defined as the time from randomization until the date of the first occurrence of one of the following events: Ipsilateral invasive breast cancer recurrence (same breast); Ipsilateral (same side of body) local regional invasive breast cancer recurrence (axilla, regional lymph nodes, chest wall, and/or skin); Distant recurrence (evidence of breast cancer in any anatomic site);Death attributable to any cause; Contralateral (opposite side of the body) invasive breast cancer or Second primary non-breast invasive cancer. | Event driven (until data cutoff: 29 February 2012: up to 49 months) | 
| Percentage of Participants With Invasive Disease-free Survival (IDFS) Events | IDFS, was a composite endpoint defined as the time from randomization until the date of the first occurrence of one of the following events: Ipsilateral invasive breast cancer recurrence (same breast); Ipsilateral (same side of body) local regional invasive breast cancer recurrence (axilla, regional lymph nodes, chest wall, and/or skin); Distant recurrence (evidence of breast cancer in any anatomic site);Death attributable to any cause; Contralateral (opposite side of the body) invasive breast cancer or Second primary non-breast invasive cancer. The percentage of participants with and without IDFS Events by the time of the data cutoff is presented. | Event driven (until data cutoff: 29 February 2012 up to 49 months) | 
| Time to Invasive Disease-free Survival (IDFS) Event Excluding Second Primary Non-Breast Invasive Cancer | IDFS, was a composite endpoint defined as the time from randomization until the date of the first occurrence of one of the following events: Ipsilateral invasive breast cancer recurrence (same breast); Ipsilateral (same side of body) local regional invasive breast cancer recurrence (axilla, regional lymph nodes, chest wall, and/or skin); Distant recurrence (evidence of breast cancer in any anatomic site); Death attributable to any cause; Contralateral (opposite side of the body) invasive breast cancer. | Event driven (until data cutoff: 29 February 2012: up to 49 months) | 
| Percentage of Participants With Invasive Disease-free Survival (IDFS) Events Excluding Second Primary Non-Breast Invasive Cancer | IDFS, was a composite endpoint defined as the time from randomization until the date of the first occurrence of one of the following events: Ipsilateral invasive breast cancer recurrence (same breast); Ipsilateral (same side of body) local regional invasive breast cancer recurrence (axilla, regional lymph nodes, chest wall, and/or skin); Distant recurrence (evidence of breast cancer in any anatomic site); Death attributable to any cause; Contralateral (opposite side of the body) invasive breast cancer. Percentage of participants with and without IDFS Events by the time of data cutoff is presented. | Event driven (until data cutoff: 29 February 2012: up to 49 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Overall Survival (OS) Event | OS was defined as the time from randomization to death attributable to any cause. Patients for whom no death is captured in the clinical database up to the clinical cut-off date are censored at the last time they were known to be alive. | Event driven (until data cutoff: 29 February 2012: up to 49 months) | 
| Time to Overall Survival (OS) Event | OS was defined as the time from randomization to death attributable to any cause. Patients for whom no death is captured in the clinical database up to the clinical cut-off date are censored at the last time they were known to be alive. | Event driven (until data cutoff: 30 June 2014: up to 77 months) | 
| Percentage of Participants With Overall Survival (OS) Event | OS was defined as the time from randomization to death attributable to any cause. Patients for whom no death is captured in the clinical database up to the clinical cut-off date are censored at the last time they were known to be alive. | Event driven (until data cut off: 29 February 2012: up to 49 months) | 
| Percentage of Participants With Overall Survival (OS) Event | OS was defined as the time from randomization to death attributable to any cause. Patients for whom no death is captured in the clinical database up to the clinical cut-off date are censored at the last time they were known to be alive. | Event driven (until data cut off: 30 June 2014: up to 77 months) | 
| Time to Breast Cancer-Free Interval (BCFI) Event | BCFI is defined as the time from randomization until the date of the first occurrence of one of the following events: Ipsilateral local/regional invasive breast cancer recurrence or distant breast cancer recurrence; Contralateral invasive breast cancer; Ipsilateral or contralateral Ductal carcinoma in situ or Death only from breast cancer cause. | Event driven (until data cutoff: 29 February 2012: up to 49 months) | 
| Percentage of Participants With Breast Cancer-Free Interval (BCFI) Events | BCFI is defined as the time from randomization until the date of the first occurrence of one of the following events: Ipsilateral local/regional invasive breast cancer recurrence or distant breast cancer recurrence; Contralateral invasive breast cancer; Ipsilateral or contralateral DCIS or Death only from breast cancer cause. Percentage of participants with and without BCFI events by the time of the data cutoff is presented. | Event driven (until data cutoff: 29 February 2012: up to 49 months) | 
| Time to Disease-Free Survival (DFS) Event | DFS is defined as the time from randomization until the date of the first occurrence of one of the following events: Ipsilateral invasive breast cancer recurrence (same breast); Ipsilateral (same side of body) local regional invasive breast cancer recurrence (axilla, regional lymph nodes, chest wall, and/or skin); Distant recurrence (evidence of breast cancer in any anatomic site); Death attributable to any cause; Contralateral (opposite side of the body) invasive breast cancer, Second primary non-breast invasive cancer or New diagnosis of an ipsilateral or contralateral Ductal carcinoma in situ (DCIS). | Event driven (until data cutoff: 29 February 2012: up to 49 months) | 
| Percentage of Participants With Disease-Free Survival (DFS) Events | DFS is defined as the time from randomization until the date of the first occurrence of one of the following events: Ipsilateral invasive breast cancer recurrence (same breast); Ipsilateral (same side of body) local regional invasive breast cancer recurrence (axilla, regional lymph nodes, chest wall, and/or skin); Distant recurrence (evidence of breast cancer in any anatomic site); Death attributable to any cause; Contralateral (opposite side of the body) invasive breast cancer, Second primary non-breast invasive cancer or New diagnosis of an ipsilateral or contralateral Ductal carcinoma in situ (DCIS). Percentage of Participants with and without DFI Events by the time of the data cut-off is presented. | Event driven (until data cutoff: 29 February 2012: up to 49 months) | 
| Time to Distant Disease-Free Survival (DDFS) Event | DDFS is defined as the time from randomization until the date of the first occurrence of one of the following events: Distant recurrence; Death attributable to any cause; Second primary non-breast invasive cancer (with the exception of non-melanoma Skin cancers). | Event driven (until data cutoff: 29 February 2012: up to 49 months) | 
| Percentage of Participants With Distant Disease-Free Survival (DDFS) Events | DDFS is defined as the time from randomization until the date of the first occurrence of one of the following events: Distant recurrence; Death attributable to any cause; Second primary non-breast invasive cancer (with the exception of non-melanoma Skin cancers). Percentage of participants with and without DDFS Events by the time of the data cutoff is presented. | Event driven (until data cutoff: 29 February 2012: up to 49 months) | 
| Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) and Deaths | An adverse event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is Life-Threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. | Through end of study: 30 June 2014: up to 77 months |