Impact of Pegfilgrastim on Trastuzumab Anti-tumor Effect and ADCC in Operable HER2+ Breast Cancer Breast Cancer
- Conditions
- HER2-positive Breast CancerOperable Breast Cancer
- Registration Number
- NCT03571633
- Lead Sponsor
- Centre Leon Berard
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Female
- Target Recruitment
- 90
Inclusion Criteria:<br><br> - Female patients aged = 18 years at time of inform consent signature.<br><br> - Histologically proven HER2 positive breast cancer defined as 3+ staining intensity<br> by immunohistochemistry (IHC) or a 2+ IHC staining intensity and HER2 gene<br> amplification by FISH.Note: HER2 status will be determined as per institutional<br> practice.<br><br> - Operable breast tumor with tumor size and staging: > 20 mm, cN0 or cN1, M0 before<br> any AC or FEC chemotherapy, and at least one measurable lesion =10 mm in longest<br> diameter at inclusion according to RECIST 1.1.<br><br> - No radiological sign of disease progression at time of randomisation.<br><br> - Patient previously treated by 4 cycles of AC or 3 to 4 cycles of FEC without febrile<br> neutropenia and without prior pegfilgrastim treatment.<br><br> - Availability of a representative formalin-fixed paraffin-embedded (FFPE) tumor<br> specimen from initial diagnosis (i.e. an archival paraffin block is preferred; or at<br> least 20 unstained slides) with its histological report.<br><br> - Eastern Cooperative Oncology Group (ECOG) performance status = 2<br><br> - Adequate organ function as defined by the following lab tests (to be carried out<br> within 7 days prior C1D1):Bone marrow (Absolute neutrophil count = 1.5 x 109/L,<br> Platelet count > 100 x 109/L, (without transfusion within 21 days prior to C1D1),<br> Hemoglobin value = 9 g/dL), Renal function (Calculated creatinine clearance by MDRD<br> or CKD-EPI >50 mL/min/1.73m2 or serum creatinine < 1.5ULN), Liver function (Alanine<br> aminotransferase (ALT) and aspartate aminotransferase (AST) = 3ULN, Total serum<br> bilirubin = 1.5 ULN (except for patients with Gilbert disease for whom a total serum<br> bilirubin =3 ULN is acceptable), Coagulation (INR and aPTT= 1.5 ULN)<br><br> - Adequate cardiac function with Mean resting corrected QT interval (QTc), calculated<br> using Fridericia's formula, =470ms obtained from 3 electrocardiograms (ECGs) and<br> Systolic blood pressure <160mmHg and Diastolic blood pressure <100mmHg (hypertension<br> controlled by standard medical treatment is allowed)<br><br> - Women of childbearing potential (entering the study after a confirmed menstrual<br> period and who have a negative pregnancy test within 7 days before C1D1) must agree<br> to use two methods of medically acceptable forms of contraception from the date of<br> negative pregnancy test to 3 months after the last study drug intake<br><br> - Patients should be able and willing to comply with study visits and procedures as<br> per protocol<br><br> - Patients should understand, sign, and date the written voluntary informed consent<br> form at the screening visit prior to any protocol-specific procedures performed.<br><br> - Patients must be covered by a medical insurance.<br><br>Exclusion Criteria:<br><br> - Patients with inflammatory breast cancer.<br><br> - Previous exposure to pegfilgrastim or trastuzumab. Note: the use of filgrastim (non<br> pegylated form only) is authorized prior to the randomisation.<br><br> - Patients requiring the concomitant use of any forbidden treatment including: Any<br> other anti-cancer treatments not listed in the protocol, including chemotherapy,<br> radiotherapy, immunotherapy, targeted therapy or biologic therapy for cancer<br> treatment, Any investigational treatment.<br><br> - Any contra-indication to trastuzumab, paclitaxel, and pegfilgrastim respective SPCs<br> including:Hypersensitivity to trastuzumab, murine proteins, or to any of the<br> excipients listed in trastuzumab SPC, Severe dyspnea at rest due to complications of<br> advanced malignancy or requiring supplementary oxygen therapy, Hypersensitivity to<br> pegfilgrastim or filgrastim, or to any of the excipients listed in SPC, Hereditary<br> problems of fructose intolerance, Hypersensitivity to paclitaxel or to any<br> excipient, particularly macrogolglycerol ricinoleate, Patients with history of or<br> active cardiac disease including myocardial infarction (MI), angina pectoris<br> requiring medical treatment, congestive heart failure NYHA (New York Heart<br> Association) Class =II, other cardiomyopathy, cardiac arrhythmia requiring medical<br> treatment, clinically significant cardiac valvular disease, and hemodynamic<br> effective pericardial effusion.<br><br> - Active secondary malignancy unless this malignancy is not expected to interfere with<br> the evaluation of study endpoints and is approved by the sponsor. Examples of the<br> latter include basal or squamous cell carcinoma of the skin, in-situ carcinoma of<br> the cervix. Patients with a completely treated prior malignancy and no evidence of<br> disease for = 2 years are eligible.<br><br> - Pregnant or breast-feeding female patients.
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Pathological complete response rate (pCR)
- Secondary Outcome Measures
Name Time Method Disease Free survival;Time to relapse;Overall survival;Adverse events reporting