Neoadjuvant 5-fluorouracil, Epirubicin and Cyclophosphamide (FEC) Followed by Weekly Paclitaxel and Trastuzumab in Her2 Positive Breast Cancer

Study Overview
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Brief Summary
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The main purpose of this study is to confirm the high pathologic complete response rate after neoadjuvant chemotherapy with FEC followed by weekly paclitaxel and concurrent trastuzumab in Human Epidermal growth factor receptor2 (HER2) positive non operable breast cancer

Official Title
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Neoadjuvant Therapy With FEC Followed by Weekly Paclitaxel and Concurrent Trastuzumab in Her2 Positive Non Operable Breast Cancer. Phase II Study.

Conditions
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HER-2 Positive Breast Cancer

Intervention / Treatment
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* Drug: Trastuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Performance StatusEstearn Cooperative Oncology Group (ECOG) 0-1 Histologically confirmed invasive breast cancer, Primary tumour greater ≥ 2 cm diameter, measured by clinical examination and mammography or echography or Nuclear Magnetic Resonance (NMR) candidate to neoadjuvant chemotherapy , Any N, No evidence of metastasis (M0); Over expression and/or amplification of HER2 in the invasive component of the primary tumour according to one of the following definitions: 3+ over expression by immunohistochemistry (IHC) (> 30% of invasive tumour cells), 2+ or 3+ (in 30% o less neoplastic cells) overexpression by IHC and in situ hybridization (FISH/CISH) test demonstrating Her2 gene amplication , Her 2 gene amplication by FISH/CISH (ratio > 2.2); Known hormone receptor status Hematopoietic status: absolute neutrophil count ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L, Hepatic status: serum total bilirubin ≤ 1.5 x ULN. In the case of known Gilbert's syndrome a higher serum total bilirubin (< 2 x ULN) is allowed, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times ULN, alkaline phosphatase ≤ 2.5 times ULN; Renal status: a. Creatinine ≤ 2.0 mg/dL; Cardiovascular: a. baseline left ventricular ejection fraction (LVEF) ≥ 50% measured by echocardiography or multigate acquisition scan (MUGA); For women of childbearing potential negative serum pregnancy test Written informed consent. Exclusion Criteria: Male gender Pregnant or lactating women Received any prior treatment for primary invasive breast cancer Known history of uncontrolled or symptomatic angina, clinically significant arrhythmias, congestive heart failure, transmural myocardial infarction, uncontrolled hypertension (> 180/110), unstable diabetes mellitus, dyspnoea at rest or chronic therapy with oxygen; Active or uncontrolled infection, Dementia altered mental status or any psychiatric condition that would prevent the under standing or rendering of informed consent, Concurrent neoadjuvant cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy other than the trial therapies), Previous or concomitant malignancy within the past 3 years EXCEPT adequately treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix. Concurrent disease or condition that would have make the subject inappropriate for study participation or any serious medical disorder that would interfere with the subject's safety.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FEC-paclitaxel-trastuzumab<br>fluorouracil 600 mg/m2; epirubicin 90 mg/m2; cyclophosphamide 600 mg/m2 for 4 cycles followed by paclitaxel 80 mg/m2/week in combination with trastuzumab for 12 weeks | Drug: Trastuzumab<br>* neoadjuvant FEC (fluorouracil, epirubicin, cyclophosphamide) followed by weekly paclitaxel and concomitant trastuzumab<br>* Other names: herceptin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pathologic complete response |  | at definitive surgery within 4 weeks after the last dose of paclitaxel and concurrent trastuzumab | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety and tolerability | safety and tolerability will be assessed by standard clinical and laboratory tests (hematology, serum chemistry). Toxicity grade is defined by the NCI Common Toxicity Criteria (CTC) Adverse Event (AE) v 3.0 | one year | 
| cardiotoxicity |  | one year | 
| disease free survival |  | one year | 
| overall survival |  | one year | 
| rate of conversion from radical to conservative surgery |  | definitive surgery | 
| potential biomarkers of trastuzumab resistance |  | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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her2 positive breast cancer, her2 positive non operable breast cancer, her2 positive locally advanced breast cancer, neoadjuvant trastuzumab, pathologic complete response