Clinical trial NCT01340430: Neoadjuvant 5-fluorouracil, Epirubicin and Cyclophosphamide (FEC) Followed by Weekly Paclitaxel and Trastuzumab in Her2 Positive Breast Cancer
Official title: Neoadjuvant Therapy With FEC Followed by Weekly Paclitaxel and Concurrent Trastuzumab in Her2 Positive Non Operable Breast Cancer. Phase II Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HER-2 Positive Breast Cancer
Keywords: her2 positive breast cancer
her2 positive non operable breast cancer
her2 positive locally advanced breast cancer
neoadjuvant trastuzumab
pathologic complete response
Lead sponsor: IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
Sponsor class: OTHER
First posted: 2011-04-22
Enrollment: 43
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: Inclusion Criteria

1. Performance StatusEstearn Cooperative Oncology Group (ECOG) 0-1
2. Histologically confirmed invasive breast cancer,
3. Primary tumour greater ≥ 2 cm diameter, measured by clinical examination and mammography or echography or Nuclear Magnetic Resonance (NMR) candidate to neoadjuvant chemotherapy ,
4. Any N,
5. No evidence of metastasis (M0);
6. Over expression and/or amplification of HER2 in the invasive component of the primary tumour according to one of the following definitions:
7. 3+ over expression by immunohistochemistry (IHC) (\> 30% of invasive tumour cells),
8. 2+ or 3+ (in 30% o less neoplastic cells) overexpression by IHC and in situ hybridization (FISH/CISH) test demonstrating Her2 gene amplication ,
9. Her 2 gene amplication by FISH/CISH (ratio \> 2.2);
10. Known hormone receptor status
11. Hematopoietic status:

    1. absolute neutrophil count ≥ 1.5 x 109/L,
    2. platelet count ≥ 100 x 109/L,
12. Hepatic status:

    1. 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,
    2. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times ULN,
    3. alkaline phosphatase ≤ 2.5 times ULN;
13. Renal status:

    a. Creatinine ≤ 2.0 mg/dL;
14. Cardiovascular:

    a. baseline left ventricular ejection fraction (LVEF) ≥ 50% measured by echocardiography or multigate acquisition scan (MUGA);
15. For women of childbearing potential negative serum pregnancy test
16. Written informed consent.

Exclusion Criteria:

1. Male gender
2. Pregnant or lactating women
3. Received any prior treatment for primary invasive breast cancer
4. 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;
5. Active or uncontrolled infection,
6. Dementia altered mental status or any psychiatric condition that would prevent the under standing or rendering of informed consent,
7. Concurrent neoadjuvant cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy other than the trial therapies),
8. 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.
9. 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.

Primary outcomes:
measure: pathologic complete response
timeFrame: at definitive surgery within 4 weeks after the last dose of paclitaxel and concurrent trastuzumab
Secondary outcomes:
measure: safety and tolerability
timeFrame: one year
measure: cardiotoxicity
timeFrame: one year
measure: disease free survival
timeFrame: one year
measure: overall survival
timeFrame: one year
measure: rate of conversion from radical to conservative surgery
timeFrame: definitive surgery
measure: potential biomarkers of trastuzumab resistance
timeFrame: one year
Other outcomes:
Locations:
city: Genoa
country: Italy
facility: Istituto Nazionale per La Ricerca sul Cancro (IST)
state: Ge
city: Perugia
country: Italy
facility: Ospedale S. Maria della Misericordia - Oncologia Medica
state: PG
city: Candiolo
country: Italy
facility: Fondazione del Piemonte per l'Oncologia - IRCC di Candiolo
state: TO
city: Torino
country: Italy
facility: Ospedale Ostetrico Ginecologico S. Anna Di Torino - Oncologia Medica
state: To
city: Torino
country: Italy
facility: Ospedale Mauriziano Umberto I - Ginecologia Oncologica
state: TO
city: Negrar
country: Italy
facility: Ospedale Sacro Cuore - Don Calabria - Oncologia Medica
state: VR
Study officials:
affiliation: National Institute For Cancer Reasearch
name: Lucia Del Mastro, MD
role: PRINCIPAL_INVESTIGATOR
References: