Locally advanced breast cancer Cancer Malignant neoplasm of the breast
Conditions
Interventions
All patients will receive the same intravenous neoadjuvant chemotherapy regimen: doxorubicin 60 mg/m^2 plus paclitaxel 150 mg/m^2 administered over three hours of infusion 3-weekly for three cycles, f
Sponsors
Fondazione Michelangelo (Italy)
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: 1. Female patients, presenting for the first time with locally advanced breast cancer, who have not received any previous treatment for an invasive malignancy 2. Aged greater than or equal to 18 years 3. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1 4. Histologically proven diagnosis of breast cancer 5. Patients may have HER2-negative or -positive disease. HER2-positive disease is defined as follows: 5.1. Overexpresses HER2 by immunohistochemistry (2+ or 3+) 5.2. Has c-erbB2/HER2 amplification according to fluorescent in situ hybridisation (FISH). Patients in the parallel observational study must have HER2-negative tumours (0 or 1+) on immunohistochemistry. 6. The primary tumour must be T4 (skin or nipple invasion, peau d'orange, extension into chest wall or inflammatory carcinoma); any T plus N1a, N2 or N3; or any T plus involvement of ipsilateral supraclavicular lymph nodes 7. At least one measurable lesion according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria (Note: the minimum indicator lesion size is defined as greater than or equal to 20 mm, measured by palpation), except for inflammatory carcinoma (T4d) 8. Have hormonal receptors (oestrogen receptor [ER] and progesterone receptor [PgR]) assessed 9. Signed written informed consent (approved by the Institutional Review Board [IRB]/Independent Ethics Committee [IEC]) obtained prior to any study specific screening procedures 10. Able to comply with the protocol
Exclusion criteria
Exclusion criteria: 1. Pregnant or lactating women. Documentation of a negative pregnancy test must be available for pre-menopausal women with intact reproductive organs and for women less than one year after the menopause. 2. Women of childbearing potential unless: 2.1. Surgically sterile 2.2. Using adequate measures of contraception, e.g., intra-uterine device or barrier method of contraception in conjunction with spermicidal jelly 3. Evidence of metastases, with the exception of ipsilateral supraclavicular nodes 4. Bilateral breast cancer 5. Previous treatment with chemotherapy or hormonal therapy or any prior therapy with an anti-HER2 therapy for any malignancy 6. Previous extensive radiotherapy or major surgery for any malignancy 7. Previous or concomitant malignancy of any type, except adequately treated basal cell carcinoma of the skin or in situ cervix cancer 8. Treatment with any investigational drug within 30 days before beginning of treatment with study drugs 9. Patients with New York Heart Association (NYHA) class greater than or equal to II heart disease 10. Patients with a left ventricular ejection fraction (LVEF) less than 50% by multiple gated acquisition (MUGA) scan or echocardiography 11. Other serious illness or medical condition including: 11.1. History of documented congestive cardiac failure; angina pectoris requiring antianginal medication; evidence of transmural infarction on electrocardiogram [ECG]; poorly controlled hypertension (e.g. systolic greater than 180 mmHg or diastolic greater than 100 mmHg; however, patients with hypertension which is well controlled on medication are eligible); clinically significant valvular heart disease; or high-risk uncontrolled arrhythmias 11.2. Patients with a history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant precluding informed consent or adversely affecting compliance to study drugs 11.3. Serious uncontrolled infections (bacterial or viral) or poorly controlled diabetes mellitus 12. Any of the following abnormal baseline haematological values: neutrophils less than 1.5 x 10^9/L, platelets less than 100 x 10^9/L 13. Any of the following abnormal laboratory tests: serum total bilirubin greater than 1.25 x ULN (upper limit of normal) (except for patients with clearly documented Gilbert's syndrome), alanine transaminase (ALT) or aspartate transaminase (AST) greater than 1.25 x ULN, alkaline phosphatase greater than 1.25 x ULN, serum creatinine greater than 1.5 x ULN. Hepatic metastases must be excluded as a cause of abnormal liver function tests.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Event-free survival (EFS), defined as time from randomisation to disease recurrence or progression [local, regional, distant or contralateral] or death due to any cause), measured when 86 EFS events are documented | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Pathlogical complete response (in breast pCR [bpCR] and breast and axilla pCR [tpCR]) and overall response rates, measured when all patients complete surgery 2. Cardiac safety in all three groups, measured during primary systemic therapy, before surgery and at two years after surgery 3. Overall survival in all three groups, measured after a median follow-up of 3 and 5 years from registration 4. EFS (measured from study registration) in patients with HER2-negative disease, measured after a median follow-up of 3 years | — |
Countries
Austria, Germany, Italy, Portugal, Russian Federation, Spain
Outcome results
None listed