The duration of the neoadjuvant treatment period is planned to be 12 weeks (4 cycles of 3
weeks), except in case of Inacceptable toxicity, or Patient decision, or Withdrawal of
consent, or Clinical/radiological signs of disease progression.This neoadjuvant treatment
period will be ended with a short term safety visit (STSVNeo) to be scheduled 28 days after
the last dose of study treatments (considering the latest study treatments administered).
Following the STSVNeo, patients will undergo surgery as per usual practice and pathological
response will be centrally assessed by a referent pathologist blinded for the treatment
arms.Following surgery, all patients will be treated in the adjuvant setting with trastuzumab
administered every 3 weeks for up to 12 months in both arms with clinical assessments every 3
months (cf. Réseau régional de Cancérologie,
http://espacecancer.sante-ra.fr/Pages/Accueil.aspx). In case of RH+ disease, endocrine
therapy may be initiated as per standard treatment guidelines.This adjuvant treatment period
is planned for a maximum of 12 months; except in case of Inacceptable toxicity, or Patient
decision, or Withdrawal of consent, or Clinical/radiological signs of disease progression.
All randomized and treated patients will be followed-up for relapse and survival for at least
15 months post-randomization (i.e. 1 year post-surgery).
A total of 90 patients will be randomized in the study. (45 per arm). All the data concerning
the patients will be recorded in the electronic case report form (eCRF) throughout the study
serious adverse event (SAE) reporting will be also paper-based by e-mail and/or Fax. The
sponsor will perform the study monitoring and will help the investigators to conduct the
study in compliance with the clinical trial protocol, Good Clinical Practices (GCP) and local
- Female patients aged ≥ 18 years at time of inform consent signature.
- Histologically proven HER2 positive breast cancer defined as 3+ staining intensity by
immunohistochemistry (IHC) or a 2+ IHC staining intensity and HER2 gene amplification
by FISH.Note: HER2 status will be determined as per institutional practice.
- Operable breast tumor with tumor size and staging: > 20 mm, cN0 or cN1, M0.
- No radiological sign of disease progression at time of randomisation.
- Patient previously treated by 4 cycles of AC or 3 to 4 cycles of FEC without febrile
neutropenia and without prior pegfilgrastim treatment.
- Availability of a representative formalin-fixed paraffin-embedded (FFPE) tumor
specimen from initial diagnosis (i.e. an archival paraffin block is preferred; or at
least 20 unstained slides) with its histological report.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Adequate organ function as defined by the following lab tests (to be carried out
within 7 days prior C1D1):Bone marrow (Absolute neutrophil count ≥ 1.5 x 109/L,
Platelet count > 100 x 109/L, (without transfusion within 21 days prior to C1D1),
Hemoglobin value ≥ 9 g/dL), Renal function (Calculated creatinine clearance by MDRD or
CKD-EPI >50 mL/min/1.73m2 or serum creatinine < 1.5ULN), Liver function (Alanine
aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3ULN, Total serum
bilirubin ≤ 1.5 ULN (except for patients with Gilbert disease for whom a total serum
bilirubin ≤3 ULN is acceptable), Coagulation (INR and aPTT≤ 1.5 ULN)
- Adequate cardiac function with Mean resting corrected QT interval (QTc), calculated
using Fridericia's formula, ≤470ms obtained from 3 electrocardiograms (ECGs) and
Systolic blood pressure <160mmHg and Diastolic blood pressure <100mmHg (hypertension
controlled by standard medical treatment is allowed)
- Women of childbearing potential (entering the study after a confirmed menstrual period
and who have a negative pregnancy test within 7 days before C1D1) must agree to use
two methods of medically acceptable forms of contraception from the date of negative
pregnancy test to 3 months after the last study drug intake
- Patients should be able and willing to comply with study visits and procedures as per
- Patients should understand, sign, and date the written voluntary informed consent form
at the screening visit prior to any protocol-specific procedures performed.
- Patients must be covered by a medical insurance.
- Patients with inflammatory breast cancer.
- Previous exposure to pegfilgrastim or trastuzumab. Note: the use of filgrastim (non
pegylated form only) is authorized prior to the randomisation.
- Patients requiring the concomitant use of any forbidden treatment including: Any other
anti-cancer treatments not listed in the protocol, including chemotherapy,
radiotherapy, immunotherapy, targeted therapy or biologic therapy for cancer
treatment, Any investigational treatment.
- Any contra-indication to trastuzumab, paclitaxel, and pegfilgrastim respective SPCs
including:Hypersensitivity to trastuzumab, murine proteins, or to any of the
excipients listed in trastuzumab SPC, Severe dyspnea at rest due to complications of
advanced malignancy or requiring supplementary oxygen therapy, Hypersensitivity to
pegfilgrastim or filgrastim, or to any of the excipients listed in SPC, Hereditary
problems of fructose intolerance, Hypersensitivity to paclitaxel or to any excipient,
particularly macrogolglycerol ricinoleate, Patients with history of or active cardiac
disease including myocardial infarction (MI), angina pectoris requiring medical
treatment, congestive heart failure NYHA (New York Heart Association) Class ≥II, other
cardiomyopathy, cardiac arrhythmia requiring medical treatment, clinically significant
cardiac valvular disease, and hemodynamic effective pericardial effusion.
- Active secondary malignancy unless this malignancy is not expected to interfere with
the evaluation of study endpoints and is approved by the sponsor. Examples of the
latter include basal or squamous cell carcinoma of the skin, in-situ carcinoma of the
cervix. Patients with a completely treated prior malignancy and no evidence of disease
for ≥ 2 years are eligible.
- Pregnant or breast-feeding female patients.