Operable HER2 positive breast cancer MedDRA version: 20.0 Level: LLT Classification code 10006188 Term: Breast cancer female NOS System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Neulasta
Product Name: neulasta
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: PEGFILGRASTIM
CAS Number: 208265-92-3
Current Sponsor code: ET17-057
Sponsors
CENTRE LEON BERARD
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: I1. Female patients aged = 18 years at time of inform consent signature. I2. 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. I3. Operable breast tumor with tumor size and staging: > 20 mm, cN0 or cN1, M0. I4. No radiological sign of disease progression at time of randomisation. I5. Patient previously treated by 4 cycles of AC without febrile neutropenia and without prior pegfilgrastim treatment. I6. 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. I7. Eastern Cooperative Oncology Group (ECOG) performance status = 2 (Appendix 1). I8. Adequate organ function as defined by the following lab tests (to be carried out within 7 days prior C1D1): Bone marrow: o Absolute neutrophil count ? 1.5 x 109/L, o Platelet count > 100 x 109/L, (without transfusion within 21 days prior to C1D1), o Hemoglobin value ? 9 g/dL. Renal function: o Calculated creatinine clearance by MDRD or CKD-EPI >50 mL/min/1.73m2 (Appendix 2) or serum creatinine =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: E1. Patients with inflammatory breast cancer. E2. Previous exposure to pegfilgrastim or trastuzumab. Note: the use of filgrastim (non pegylated form only) is authorized prior to the randomisation. E3. Patients requiring the concomitant use of any forbidden treatment including: o Any other anti-cancer treatments not listed in the protocol, including chemotherapy, radiotherapy, immunotherapy, targeted therapy or biologic therapy for cancer treatment, o Any investigational treatment. E4. Any contra-indication to trastuzumab, paclitaxel, and pegfilgrastim respective SPCs including ([15-17 and EMA website : http://www.ema.europa.eu/ema/): o Hypersensitivity to trastuzumab, murine proteins, or to any of the excipients listed in trastuzumab SPC, o Severe dyspnea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy, o Hypersensitivity to pegfilgrastim or filgrastim, or to any of the excipients listed in SPC, o Hereditary problems of fructose intolerance, o Hypersensitivity to paclitaxel or to any excipient, particularly macrogolglycerol ricinoleate, o 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. E5. 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. E6. Pregnant or breast-feeding female patients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the clinical impact of addition of pegfilgrastim to a neoadjuvant treatment with trastuzumab / paclitaxel;Secondary Objective: To assess the effect of pegfilgrastim on trastuzumab / paclitaxel antitumor efficacy. To assess the tolerance of the combined treatment pegfilgrastim + trastuzumab + paclitaxel. ;Primary end point(s): Pathological complete response rate (pCR) defined as ypT0 ypN0 or ypT0/is ypN0 after 12 weeks of treatment by trastuzumab + paclitaxel ± pegfilgrastim with ypT0/Tis ypN0 defined as absence of invasive cancer in the breast and axillary nodes in all surgically excised specimens.;Timepoint(s) of evaluation of this end point: At surgery (W16) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1-Disease Free survival 2-Time to relapse 3-Overall survival (OS) 4-Safety : Adverse events (AEs), blood pressure , ECG, cardiac imaginig, physical examination, laboratory safety assessments (hematological and biochemical parameters). . ;Timepoint(s) of evaluation of this end point: 1-From the date of randomisation until the date of event defined as the first documented relapse after surgery or death from any cause. Patients with no event at the time of the analysis will be censored at the date of the last available tumor assessment. 2-From the time of treatment start until the first documented relapse. 3-from the date of randomisation to the date of death from any cause. 4- From the start until 28 days after the last dose of treatment. | — |
Countries
France
Contacts
Public ContactDRCI - Phases précoces
CENTRE LEON BERARD
Outcome results
None listed