Patients with HER2-negative, early invasive unilateral breast cancer who are at risk of disease recurrence and suitable for neoadjuvant chemotherapy MedDRA version: 14.1 Level: LLT Classification code 10006283 Term: Breast neoplasm malignant female System Organ Class: 100000004864
Conditions
Sponsors
FONDAZIONE MICHELANGELO - AVANZAMENTO DELLO STUDIO E CURA DEI TUMORI
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Female patients aged 18 years or older 2. Histologically confirmed invasive unilateral breast cancer 3. HER2-negative disease (defined as 0-1+ by immunohistochemistry or 2+ by immunohistochemistry without HER2 amplification by either FISH, CISH, or other amplification tests done locally) 4. Known hormone receptor status (estrogen receptor [ER], progesterone receptor [PgR]), tumor grade and, if institutional standard permits, known Ki67 value 5. Available paraffin-embedded tumor block taken at diagnostic biopsy for central confirmation of HER2 eligibility, hormone receptor status, Ki67 value and biomarker evaluation is mandatory 6. One of the following clinical stages: a. T2, T3, T4 disease, triple negative (HER2, ER, PgR) b. T2, T3, T4 disease, ER or PgR positive and moderately differentiated or poorly differentiated tumor grade (G II-III) 7. ECOG performance status 0 or 1 8. Written informed consent to participate in the trial (approved by the Institutional Review Board [IRB]/ Independent Ethics Committee [IEC]) obtained prior to any study specific screening procedures 9. Willing and able to comply with the protocol Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 632 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 632
Exclusion criteria
Exclusion criteria: 1. Synchronous bilateral breast cancer or presence of metastatic disease (M1) 2. Surgical axillary staging procedure prior to study entry. Exceptions: 1) FNA of an axillary node is permitted for any patient, and 2) although not recommended, a pre-neoadjuvant therapy sentinel lymph node biopsy for patients with clinically negative axillary nodes is permitted 3. Pregnant or lactating women. Documentation of a negative pregnancy test must be available for premenopausal women with intact reproductive organs and for women less than one year after the last menstrual cycle 4. Women with childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception, for example abstinence, an intra-uterine device, or double barrier method of contraception 5. Treatment including radiation therapy, chemotherapy, biotherapy, and/or hormonal therapy for the currently diagnosed breast cancer prior to study entry 6. Previous investigational treatment for any condition within 4 weeks of randomization date 7. Patients on therapy with a strong CYP3A4 inhibitor 8. Previous or concomitant malignancy of any other type that could affect compliance with the protocol or interpretation of results. Patients with curatively treated basal cell carcinoma of the skin or in situ cervix cancer are generally eligible. 9. Pre-existing motor or sensory neuropathy of grade > 1 for any reason 10. Patients with a history of hypersensitivity due to drugs containing polyoxyethylene castor oil (Cremophor EL) (e.g., ciclosporin), or hardened castor oil (e.g., vitamin preparations for injection, etc.) 11. Other serious illness or medical condition including: history of documented congestive cardiac failure; angina pectoris requiring anti-anginal medication; evidence of transmural infarction on ECG; poorly controlled hypertension (e.g. systolic >180 mm Hg or diastolic >100 mm Hg; however, patients with hypertension which is well controlled on medication are eligible); clinically significant valvular heart disease; high-risk uncontrolled arrhythmias 12. Patients with a history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant and precluding informed consent or adversely affecting compliance with study drugs 13. Serious uncontrolled infections (bacterial or viral) or poorly controlled diabetes mellitus 14. Any of the following abnormal baseline hematological values: a. Absolute Neutrophil Count (ANC) 1.5 ? ULN (upper limit of normal) (except for patients with clearly documented Gilbert’s syndrome) b. Alanine transaminase (ALT) or aspartate transaminase (AST) > 1.25 ? ULN c. Alkaline phosphatase > 2.5? ULN d. Serum creatinine > 1.5 ? ULN 16. Baseline left ventricular ejection fraction (LVEF) < 50% by echocardiography or multi-gated scintigraphic scan (MUGA)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the rate of pathologic Complete Response (pCR, defined as ypT0-Tis, ypN0) for abraxane vs paclitaxel;Secondary Objective: To compare the pCR rates in the two main subgroups of ER and/or PgR positive tumors and triple-negative tumors separately. To compare the rate of clinical overall response (cOR) after the first 4 cycles of abraxane vs paclitaxel. To compare the rate of cOR after the entire preoperative chemotherapy in the study arms. To compare the Event Free Survival (EFS, i.e. disease progression while on primary therapy or disease recurrence after surgery) in the study arms. To compare the Distant EFS (DEFS) in the study arms. To compare the Local EFS (LEFS) in the two study arms. To compare the Regional EFS (REFS) in the two study arms. To compare the overall survival (OS) in the study arms. To evaluate the tolerability of the treatment regimens. To conduct molecular and clinical analyses to assess the presence of predictive markers of benefit.;Primary end point(s): The primary endpoint is pathological complete response (pCR) defined as absence of invasive disease in breast and nodes (ypT0/ypTis, ypN0).;Timepoint(s) of evaluation of this end point: The primary endpoint will be evaluated at the time of surgery: approximately 40 months after the randomization of the first patient, that is when all the 632 patients required by sample size specifications have completed their courses of treatment and reached the surgery phase. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints are: - the rate of clinical overall response (cOR) - Event Free Survival (EFS, i.e. disease progression while on primary therapy or disease recurrence after surgery) - Distant EFS (DEFS) - Local EFS (LEFS) - Regional EFS (REFS) - overall survival (OS) - the tolerability of the treatment regimens;Timepoint(s) of evaluation of this end point: cOR will be evaluated after the first 4 cycles (approximately 40 months after the randomization of the first patient, that is when all the 632 patients required by sample size specifications have completed their courses of treatment and reached the surgery phase). The first analysis of EFS will take place 5 years and 10 years after the randomization of the first patient | — |
Countries
Australia, Austria, Germany, Italy, Russian Federation, Singapore, Spain
Contacts
Public ContactUfficio Operativo
Fondazione Michelangelo
Outcome results
None listed