Ensayo en fase III multicéntrico, internacional, abierto con dos grupos de tratamiento que evaluará bevacizumab adyuvante en el cáncer de mama triple negativo.An international multi-centre open-label 2-arm phase III trial of adjuvant bevacizumab in triple negative breast cancer. - BEATRICE
- Conditions
- Adenocarcinoma de mama inicial primario invasivo (triple negativo)Early primary invasive adenocarcinoma of the breast (triple negative phenotype)MedDRA version: 9.1Level: HLGTClassification code 10006291Term: Breast neoplasms malignant and unspecified (incl nipple)
- Registration Number
- EUCTR2007-001128-11-ES
- Lead Sponsor
- F. Hoffmann-La Roche Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 2530
Life expectancy of = 10 yrs (excluding the breast cancer diagnosis).
Must be able to fulfil all of the protocol requirements during the treatment and FU period.
PATIENT SPECIFIC AND GENERAL INCLUSION CRITERIA
1. Patient must have signed and dated an informed consent form
2. = 18 yrs old
3. ECOG Performance Status of 0 or 1
DISEASE SPECIFIC INCLUSION CRITERIA
4. Operable primary invasive carcinoma of the breast. Patients with multifocal and synchronous bilateral cancers are eligible if
-all cancers (excluding any associated ductal carcinoma-in-situ/DCIS) are of the triple negative phenotype and
-the eligibility is based on the highest stage grouping
5. Definitive loco-regional surgery has been completed
a) patients must have undergone either breast conservation surgery or a total mastectomy and the surgical margins of the resected specimen must be histologically free of invasive adenocarcinoma and DCIS.
-if the radial surgical margins are not histologically free of invasive adenocarcinoma and DCIS, these patients must proceed to a re-excision in order to obtain microscopically clear margins; when there is a close chest wall margin, no further excision is required if a boost is delivered to the tumour bed.
-surgical margins involved with lobular carcinoma-in-situ/LCIS will not be considered as a positive margin and therefore such patients would be eligible without additional resection
-post-mastectomy surgical margins must be free of gross residual tumour – when post-mastectomy margins are microscopically positive, such patients will be eligible if it is agreed that adjuvant radiotherapy to the chest wall will be delivered
b) patients must have completed one of the following axillary procedure for the pathological evaluation of axillary lymph nodes
I. sentinel node biopsy (SNB) or/and
II. sampling procedure or/and
III. axillary dissection
-patients in whom a SNB yields a metastatic nodal disease, must proceed to either the removal of additional non-sentinel lymph nodes or a completion axillary dissection to retrieve = 6 lymph nodes. Patients will be defined as having node negative disease either after SNB/sampling procedure or after = 4 axillary nodes have been removed.
6. The interval between the last loco-regional surgery (including re-excision of involved surgical margins) and randomisation must be between 4–11 weeks.
CLINICAL AND PATHOLOGIC STAGING CRITERIA REQUIREMENTS
PRIMARY TUMOUR
7. The primary tumour must be identified and by clinical and pathologic evaluation be T1a – 3
-if the ipsilateral axilla is microscopically involved the 1° tumour must be at least a pT1a (i.e. >1mm) in greatest dimension or
-if the ipsilateral axilla is uninvolved, the 1° tumour must be at least a pT1b (i.e.>5mm) in greatest dimension and according to clinically judgement it is expected that the patient would derive benefit from adjuvant chemotherapy
8. Triple negative phenotype must have been confirmed in a central laboratory
IPSILATERAL AXILLARY LYMPH NODES
9. Pathologic examination of the axillary nodes must reveal either
a) node positive disease (pN1a, pN2a or pN3a) OR
b) node negative disease (pN0)
SYSTEMIC EVALUATION
10. Chest, abdominal, and where applicable, bone imaging performed within 3 months prior to randomization did not reveal evidence of distant spread
CRITERIA FOR ADEQUATE ORGAN FUNCTION
11. Within 7 days prior to randomisation, the following criteria (according to the local lab) must be met:
a) Bone Marrow Function
-ANC =1.5 x 109/
CANCER HISTORY
1. Patients with T4 tumours (incl. inflammatory carcinomas and tumours with direct extension to chest wall or directly involving skin)
2. Patients in whom the surgeon was unable to surgically clear the axilla from all macroscopic disease / Presence of grossly microscopic evident extracapsular nodal extension.
PREVIOUS CANCER HISTORY
3. Prior history of breast cancer, incl. DCIS (patients with a history of LCIS are eligible).
4. Any previous malignancy treated with curative intent and patient has been disease-free for less than 5 years prior to randomization – exceptions are:
carcinoma in situ of the cervix, melanoma in situ, squamous or basal cell carcinoma of the skin.
5. Any prior systemic chemotherapy for any malignancy or treatment with an anti-angiogenic treatment that modifies VEGF molecular pathway. Previous chemotherapy for non-malignant disease should be discussed with a member of the medical support team.
Chemoprevention
6. Patients receiving chemoprevention with any hormonal agent such as raloxifene, tamoxifen or other SERM and not willing to discontinue these medications prior to study entry
MEDICAL HISTORY
7. Clinically significant cardiac diseases including
(a) Clinical evidence of transmural myocardial infarction
(b) Unstable angina
(c) Evidence of ischaemic heart disease (requiring antianginal medication with calcium channel blockers, nitrates and ß-blockers)
(d) High risk uncontrolled arrhythmias (ventricular tachycardia, supraventricular tachycardia not adequately rate controlled and high grade atrio-ventricular block)
(e) History of documented CHF or systolic dysfunction (LVEF < 55%)
8. Uncontrolled hypertension as defined as a systolic pressure > 150 mm Hg and/or diastolic pressure > 90 mm Hg, with or without anti-hypertensive medication. Patients with initial blood pressure elevations are eligible if initiation or adjustment of antihypertensive medication lowers pressure to meet entry criteria.
9. History of transient ischaemic attacks or cerebrovascular accident
10. When the risk for the development of venous thrombo-embolism outweighs the benefits of participating in the trial.
11. Patients on a therapeutic dose of an anticoagulant for a venous thrombo-embolism
12. History or evidence of an inherited bleeding diathesis or coagulopathy at risk of bleeding
13. Gastroduodenal ulcer(s) determined by endoscopy to be active
14. Patients with an infection requiring intravenous antibiotics at randomization
15. Patients who have any other disease, metabolic or psychological, or who have any evidence on clinical examination or special investigations (including a lab finding) which gives reasonable suspicion of a disease or condition that contraindicates the use of the investigational drug, or that may affect the patient’s compliance with study requirements, or would place the patient at higher risk of potential treatment complications
16. Pregnant or lactating women
SURGICAL HISTORY
17. Invasive procedures within 28 days prior to randomization and defined as follows: major surgical procedure, open biopsy or significant traumatic injury (placement of a vascular access device is not considered a major surgical procedure)
18. Anticipation of need for major surgical procedures (other than the required breast surgery) during the course of the study
19. Unhealed wound, skin ulcers or incompletely healed bone fracture
20. Recent history (i.e. within 6 months of randomization) of an abdominal fistula incl. any othe
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method