An international multi-centre open-label 2-arm phase III trial of adjuvant bevacizumab in triple negative breast cancer. - BEATRICE

• Register: RPEC
• Last refreshed on: 4 September 2023
• Main ID: PER-033-09
• Date of registration: 14/08/2009
• Prospective Registration: Yes
• Primary sponsor: F. HOFFMANN-LA ROCHE LTD.,
• Public title: An international multi-centre open-label 2-arm phase III trial of adjuvant bevacizumab in triple negative breast cancer. - BEATRICE
• Scientific title: An international multi-centre open-label 2-arm phase III trial of adjuvant bevacizumab in triple negative breast cancer. - BEATRICE
• Date of first enrolment: 01/01/1900
• Target sample size: 99
• Recruitment status: Complete
• URL: https://www.ins.gob.pe/ensayosclinicos/rpec/recuperarECPBNuevoEN.asp?numec=033-09
• Study type: Interventional
• Study design: International multicentre, open design, 2-arm randomized (1: 1) phase III trial in patients with triple negative and / or pseudo-basal early invasive primary breast adenocarcinoma.
• Phase: III

Countries of recruitment

Austria, Czech Republic, Finland, France, Germany, Greece, Italy, Netherlands, Peru, Poland, Portugal, Spain, Sweden, United Kindgdom

Contacts

• Name: Gabriela Cajahuaringa Loyola
• Affiliation: IQVIA RDS Peru S.R.L

• Name: Gabriela Cajahuaringa Loyola
• Affiliation: IQVIA RDS Peru S.R.L

Key inclusion & exclusion criteria

Inclusion criteria:
• All patients must have signed and dated an informed consent form
• Must be at least 18 years old
• The patient must have a clinical status (performance status) 0 or 1 on the BCOG scale
• The patient must have presented an operable primary invasive carcinoma of the breast.
• The definitive local-regional surgery has been performed
• The interval between the last local-regional operation (including the new removal of affected surgical margins) and randomization should be between 4 and 11 weeks.
• The primary tumor must be identified and be, by clinical and pathological evaluation, Tla-T3
• Central laboratory tests of the primary invasive tumor must confirm the negativity for HER2 and the expression of the endocrine receptor (ER and PgR) must be negative (ie a total Allred score of O or 2) or low (ie, a total Allred score of 3).
• The pathological examination of the axillary nodes must reveal disease with positive nodes (pNla, pN2a or pN3a) OR disease with negative nodes (pN0)
• Imaging studies of the chest, abdomen and, if applicable, bones, performed within 3 months prior to randomization do not reveal evidence of distance dissemination
• Specific criteria of organs (according to the local laboratory) must be met as a guarantee of the evidence of adequate organic function, within 7 days prior to randomization.

Exclusion criteria:
• Patients with T4 tumors (which include inflammatory carcinomas and tumors with direct extension to the chest wall or directly affecting the skin)
• Patients in whom the surgeon was not able to surgically release the axilla from all gross disease / Presence of microscopic extracapsular extension clearly visible in lymph nodes
• History of breast cancer, including DCIS. (Patients with a history of CLIS are eligible)
• Any previous malignant tumor treated with the intention of curing, of which the patient has not had relapses for less than 5 years before randomization; Exceptions are: carcinoma in situ of the cervix, flat cell carcinoma of the skin or basal cell carcinoma of the skin
• Any previous systemic chemotherapy to treat any malignant tumor, or an antiangiogenic treatment that modifies the molecular pathway of the FCEV. Prior chemotherapy for a non-malignant disease should be analyzed with a member of the medical support team.
• Patients who are receiving chemoprophylaxis with any hormonal agent, such as raloxifene, tamoxifen or other SERMs, and are not willing to stop these medications before entering the study.
• Clinically significant heart disease
• Uncontrolled hypertension, defined by a systolic pressure> 150 mm Hg and / or EXCLUSION a diastolic pressure> 90 mm Hg, with or without antihypertensive medication. The (cont.) Patients with initial blood pressure elevations are eligible if when starting to take hypertensive medication or when adjusting the doses the pressure decreases until the admission criteria are met.
• History of transient ischemic attacks (TIA) or stroke (CVA).
• The risk of developing venous thromboembolism outweighs the benefits of participating in the study.
• Patients being treated with a therapeutic dose of an anticoagulant due to venous thromboembolism (eg, deep vein thrombosis or pulmonary embolism).
• History or evidence of hemorrhagic diathesis or hereditary coagulopathy with risk of bleeding
• Gastroduodenal ulcer (s), demonstrating activity by endoscopy
• Patients with an infection that requires intravenous antibiotics at the time of randomization
• Patients with any other disease, metabolic or psychological, or who have any evidence during the physical examination or in special investigations (including a laboratory finding) that generates a reasonable suspicion that there is a disease or condition that causes the use of the drug In research it is contraindicated, or it may affect the fulfillment of the study requirements by the patient, or it may increase the patient´s risk of suffering possible complications from the treatment.
• Pregnant or breastfeeding women.
• Invasive procedures within 28 days prior to randomization, defined as follows: major surgery procedure, open pit biopsy or major traumatic injury (the placement of a vascular access device is not considered a major surgery procedure )
• Forecast the need for major surgery procedures (other than the breast operation required) during the course of the study 19. Unhealed wounds, skin ulcers or incompletely welded bone fracture
• Recent history (ie, within 6 months of randomization) of an abdominal fistula, including any other grade 4 non-GI fistula, GI perforation or intra-abdominal abscess
• Patients who require continuous daily treatment with aspirin (> 325 mg / day) or clopidogrel (> 75 mg / day)
• Women with the ability to procreate, female patients

Age minimum: 18
Age maximum: 75
Gender: Female

Health Condition(s) or Problem(s) studied

C50

Malignant neoplasm of breast

-C50 Malignant neoplasm of breast
Malignant neoplasm of breast

Intervention(s)

Group name:Arm B Type of group;1 N° of participants:1265 Intervention(s) description:Bevacizumab 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 + Standard adjuvant chemotherapy. 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.
Group name:Arm A Type of group;2 N° of participants:1265 Intervention(s) description:Standard adjuvant chemotherapy. 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.

Primary Outcome(s)

Outcome name: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.

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

Outcome name: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.

Measure:Percentage of Participants With Invasive Disease-free Survival (IDFS) Events
Timepoints:Event driven (until data cutoff: 29 February 2012 up to 49 months)

Outcome name: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.

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

Outcome name: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.

Measure:Time to Invasive Disease-free Survival (IDFS) Event
Timepoints:Event driven (until data cutoff: 29 February 2012: up to 49 months)

Secondary Outcome(s)

Outcome name: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.

Measure:Percentage of Participants With Disease-Free Survival (DFS) Events
Timepoints:Event driven (until data cutoff: 29 February 2012: up to 49 months)

Outcome name: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.

Measure:Percentage of Participants With Overall Survival (OS) Event
Timepoints:Event driven (until data cut off: 30 June 2014: up to 77 months)

Outcome name: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.

Measure:Time to Overall Survival (OS) Event
Timepoints:Event driven (until data cutoff: 30 June 2014: up to 77 months)

Outcome name: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.
Measure:Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) and Deaths
Timepoints:Through end of study: 30 June 2014: up to 77 months

Outcome name: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.

Measure:Percentage of Participants With Distant Disease-Free Survival (DDFS) Events
Timepoints:Event driven (until data cutoff: 29 February 2012: up to 49 months)

Outcome name: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.

Measure:Time to Breast Cancer-Free Interval (BCFI) Event
Timepoints:Event driven (until data cutoff: 29 February 2012: up to 49 months)

Outcome name: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.

Measure:Percentage of Participants With Breast Cancer-Free Interval (BCFI) Events
Timepoints:Event driven (until data cutoff: 29 February 2012: up to 49 months)

Outcome name: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.

Measure:Time to Overall Survival (OS) Event
Timepoints:Event driven (until data cutoff: 29 February 2012: up to 49 months)

Outcome name: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.

Measure:Percentage of Participants With Overall Survival (OS) Event
Timepoints:Event driven (until data cut off: 29 February 2012: up to 49 months)

Outcome name: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).

Measure:Time to Distant Disease-Free Survival (DDFS) Event
Timepoints:Event driven (until data cutoff: 29 February 2012: up to 49 months)

Outcome name: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).

Measure:Time to Disease-Free Survival (DFS) Event
Timepoints:Event driven (until data cutoff: 29 February 2012: up to 49 months)

Secondary ID(s)

EUCTR2007-001128-11-GB

NCT00528567

Ethics review

Status: Approved
Approval date: 09/01/2009
Contact:

[e-mail] - [e-mail]

Universidad San Martin de Porres

999098514

[e-mail] - [e-mail]

Status: Approved
Approval date: 12/02/2009
Contact:

[e-mail]

Hospital Nacional Edgardo Rebagliati Martins

2654901-3080 2640516

[e-mail]