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

Phase 3

Completed

Conditions: Breast Cancer

Interventions: Drug: Standard adjuvant chemotherapy
Drug: Bevacizumab

Registration Number: NCT00528567

Lead Sponsor: Hoffmann-La Roche

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 2591

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Chemotherapy	Standard adjuvant chemotherapy	Participants randomized to receive standard adjuvant chemotherapy as prescribed.
Bevacizumab and Chemotherapy	Standard adjuvant chemotherapy	Participants randomized to receive bevacizumab in combination with chemotherapy as prescribed.
Bevacizumab and Chemotherapy	Bevacizumab	Participants randomized to receive bevacizumab in combination with chemotherapy as prescribed.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Breast Cancer-Free Interval (BCFI) Events	Event driven (until data cutoff: 29 February 2012: up to 49 months)	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.
Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) and Deaths	Through end of study: 30 June 2014: up to 77 months	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.
Percentage of Participants With Overall Survival (OS) Event	Event driven (until data cut off: 30 June 2014: up to 77 months)	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.
Time to Breast Cancer-Free Interval (BCFI) Event	Event driven (until data cutoff: 29 February 2012: up to 49 months)	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.
Time to Overall Survival (OS) Event	Event driven (until data cutoff: 30 June 2014: up to 77 months)	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.
Time to Disease-Free Survival (DFS) Event	Event driven (until data cutoff: 29 February 2012: up to 49 months)	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 Distant Disease-Free Survival (DDFS) Events	Event driven (until data cutoff: 29 February 2012: up to 49 months)	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.
Percentage of Participants With Disease-Free Survival (DFS) Events	Event driven (until data cutoff: 29 February 2012: up to 49 months)	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.
Time to Distant Disease-Free Survival (DDFS) Event	Event driven (until data cutoff: 29 February 2012: up to 49 months)	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).