Resected node-positive or high risk node-negative, invasive HER2-positive breast cancer. MedDRA version: 9.1 Level: HLGT Classification code 10006291 Term: Breast neoplasms malignant and unspecified (incl nipple)
Conditions
Sponsors
F. Hoffmann-La Roche Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: See Section 4 of protocol and Annex A for full details: 1. The patient must have consented to participate and must have signed and dated both EC-approved consent forms. The pre-entry central HER2 testing consent form must be signed before tumor material is sent to the central laboratory for HER2 testing 2. Patients must be female 3. The patient must be >=18 years old. 4. The patient must have an ECOG performance status of 0 or 1. 5. The tumor must be unilateral invasive adenocarcinoma of the breast on histologic examination. 6. The breast cancer must be HER2-positive based on test results as follows: *Local testing should demonstrate that tumor is IHC 2+ or 3+ or is considered to be HER2-positive for gene amplification by FISH, CISH, or other ISH method. If local ISH test results are considered equivocal, tumor can be submitted for central HER2 testing. *Central testing (a requirement for ALL patients) must demonstrate that the tumor is HER2-positive which is defined as IHC 3+ and/or FISH-positive. 7.Patients must have ER analysis performed on the primary tumor prior to randomization. If ER analysis is negative, then PgR analysis must also be performed. 8.Patients must have undergone either a total mastectomy or lumpectomy. 9.The interval between the last surgery for breast cancer and randomization must be no more than 84 days and not less than 28 days. 10. For patients who undergo lumpectomy, the margins of the resected specimen must be histologically free of invasive tumor and DCIS as determined by the local pathologist. 11. For patients who undergo mastectomy, margins must be free of gross residual tumor. Patients with microscopic positive margins are eligible. 12. All of the following staging criteria (according to the 6th edition of the AJCC Cancer Staging Manual) must be met: * By pathologic evaluation, primary tumor must be pT1-3; * By pathologic evaluation, ipsilateral nodes must be pN0, pN1 (pN1mi, pN1a, pN1b, pN1c), pN2a, pN3a, or pN3b * If pN0, must also meet at least one of the following criteria: * Pathologic tumor size > 2.0 cm; * ER negative and PgR negative; * Histologic and/or nuclear grade 2 (intermediate) or 3 (high); or * Age ULN are eligible for inclusion in the study if liver imaging (CT, MRI, or PET scan), performed within 3 months prior to randomization, does not demonstrate metastatic disease and meets other testing parameters as described in Criterion 16 below. 15. Patients with alkaline phosphatase that is > ULN but <= 2.5 x ULN are eligible for inclusion in the study if a bone scan, PET scan, or PET-CT scan performed within
Exclusion criteria
Exclusion criteria: See Section 4 of protocol and Annex A for full details: Disease-specific : 1. Inflammatory breast cancer. 2. Synchronous or previous contralateral invasive breast cancer Clinical Staging : 3. Definitive clinical or radiologic evidence of metastatic disease. (Chest imaging [mandatory for all patients] and other imaging [if required] must have been performed within 3 months prior to randomization.) Cancer History : 4.History of ipsilateral invasive breast cancer regardless of treatment or ipsilateral DCIS treated with excision and RT. 5. History of non-breast malignancies within the 5 years prior to study entry, except for the following: carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous cell carcinoma of the skin. 6. Previous therapy with anthracyclines, taxanes, carboplatin, trastuzumab, or bevacizumab for any malignancy. 7. Treatment including RT, chemotherapy, and/or targeted therapy, administered for the currently diagnosed breast cancer prior to randomization. Endocrine Therapy : 8. Continued therapy with any hormonal agent such as raloxifene or tamoxifen (or other SERM) or an aromatase inhibitor. (Patients are eligible if these medications are discontinued prior to randomization.) Medical History : 9. Cardiac disease (history of and/or active disease) that would preclude the use of the drugs included in the treatment regimens. This includes but is not confined to: * Active cardiac disease : ** angina pectoris that requires the use of anti-anginal medication; ** ventricular arrhythmias except for benign premature ventricular contractions; ** supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication; ** conduction abnormality requiring a pacemaker; ** valvular disease with documented compromise in cardiac function; and ** symptomatic pericarditis. * History of cardiac disease: ** myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LV function; ** history of documented CHF; and ** documented cardiomyopathy. 10. Uncontrolled hypertension defined as systolic BP > 150 mmHg or diastolic BP > 90 mmHg, with or without anti-hypertensive medication. (BP must be assessed within 28 days prior to randomization.) Patients with initial BP elevations are eligible if initiation or adjustment of BP medication lowers pressure to meet entry criteria. 11. History of hypertensive crisis or hypertensive encephalopathy. 12. History of TIA or CVA. 13. History of any arterial thrombotic event within 12 months before randomization. 14. Symptomatic peripheral vascular disease. 15. Intrinsic lung disease resulting in dyspnea. 16. Unstable diabetes mellitus. 17. Active infection or chronic infection requiring chronic suppressive antibiotics. 18. Any significant bleeding within 6 months before randomization, exclusive of menorrhagia in premenopa
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether the addition of bevacizumab to the two designated regimens of chemotherapy + trastuzumab (TCHB->HB; THB->FEC->HB) will improve invasive disease-free survival (IDFS) relative to the two designated regimens of chemotherapy + trastuzumab (TCH->H; TH->FEC->H).; Secondary Objective: Please refer to protocol section 3.2 for the list of secondary objective related to 1. Invasive disease-free survival (IDFS) within chemotherapy cohorts 2. Disease-free survival (DFS) 3. Overall survival (OS) 4. Recurrence-free interval (RFI) 5. Distant recurrence-free interval (DRFI) 6. Cardiac toxicity 7. Non-cardiac toxicity 8. Molecular predictors of efficacy and cardiac dysfunction ;Primary end point(s): Invasive disease-free survival, defined as time to local recurrence following mastectomy, invasive local recurrence in the ipsilateral breast following lumpectomy, regional recurrence, distant recurrence, invasive contralateral breast cancer, second primary cancer (other than squamous or basal cell carcinoma of the skin, carcinoma in situ of the cervix, colon carcinoma in situ, or lobular carcinoma in situ of the breast), or death from any cause prior to recurrence or second primary cancer. | — |
Countries
Austria, Belgium, Bulgaria, Czech Republic, Estonia, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Portugal, Slovakia, Slovenia, Spain, Sweden, United Kingdom
Outcome results
None listed