Clinical trial NCT01822314: Neoadjuvant Chemotherapy With Nab-paclitaxel in Women With HER2-negative High-risk Breast Cancer
Official title: Neoadjuvant Chemotherapy With Nab-paclitaxel in Women With HER2-negative High-risk Breast Cancer " ETNA (Evaluating Treatment With Neoadjuvant Abraxane)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: breast
cancer
unilateral
non metastatic
HER2 negative
Lead sponsor: Fondazione Michelangelo
Sponsor class: OTHER
First posted: 2013-04-02
Enrollment: 632
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the efficacy of neoadjuvant weekly nab-paclitaxel followed by Adriamycin, Cyclophosphamide (AC) or Epirubicin, Cyclophosphamide (EC) or Fluorouracil,Epirubicin,Cyclophosphamide (FEC)compared with neoadjuvant weekly solvent-based paclitaxel followed by AC or EC or FEC in terms of rate of pathological complete remissions at surgery.

Detailed description: In this study, eligible and consenting patients will be randomized to receive either 4 cycles of weekly abraxane (nab-paclitaxel) followed by 4 cycles of an anthracycline-containing regimen or 4 cycles of weekly paclitaxel followed by 4 cycles of an anthracycline-containing regimen.The anthracycline regimen (AC, EC or FEC) will be chosen by the investigator at the participating sites.

Before randomization patients will be stratified according to Disease stage \[operable (tumor stage: T2N0-1; T3N0) and locally advanced (T3N1;T4, any N2-3)\] and Tumor subtype \[luminal B intermediate (HER2 negative, ER or PGR positive, Ki67 from 14% to 20%) vs luminal B high (HER2 negative, ER or PGR positive, Ki67 \>20%) vs triple negative tumors (HER2 negative, ER negative and PgR negative, Ki67 any value)\]. Tumor subtype will be confirmed at two selected referral laboratories.

Neoadjuvant chemotherapy will be followed by definite surgery and irradiation as per international and local guidelines.

During neoadjuvant chemotherapy patients will be assessed for safety and efficacy as detailed in the protocol.

After definite surgery patients will be followed for approximately 10 years according to local procedures

Eligibility criteria: Inclusion Criteria:

* Female patients aged 18 years or older
* Histologically confirmed invasive unilateral breast cancer
* HER2-negative disease
* Known hormone receptor status (estrogen receptor \[ER\], progesterone receptor \[PgR\]), tumor grade and, if institutional standard permits, known Ki67 value
* Available paraffin-embedded tumor block taken at diagnostic biopsy for central confirmation of HER2 eligibility, hormone receptor status, Ki67 value and biomarker evaluation is mandatory
* One of the following clinical stages:
* T2, T3, T4 disease, triple negative (HER2, ER, PgR)
* T2, T3, T4 disease, ER or PgR positive and moderately differentiated or poorly differentiated tumor grade (G II-III)
* ECOG performance status 0 or 1
* Written informed consent to participate in the trial (approved by the Institutional Review Board \[IRB\]/ Independent Ethics Committee \[IEC\]) obtained prior to any study specific screening procedures
* Willing and able to comply with the protocol

Exclusion Criteria:

* Synchronous contralateral breast cancer or presence of metastatic disease (M1). Exception: contralateral insitu ductal cancer
* Surgical axillary staging procedure prior to study entry. Exceptions: 1) Fine needle aspiration (FNA) of an axillary node is permitted for any patient, and 2) although not recommended, a pre-neoadjuvant therapy sentinel lymph node biopsy for patients with clinically negative axillary nodes is permitted
* Pregnant or lactating women.
* Women with childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception, for example abstinence, an intra-uterine device, or double barrier method of contraception
* Treatment including radiation therapy, chemotherapy, biotherapy, and/or hormonal therapy for the currently diagnosed breast cancer prior to study entry
* Previous investigational treatment for any condition within 4 weeks of randomization date
* Patients on therapy with a strong CYP3A4 inhibitor and on therapy with Warfarin (Coumadin)
* Previous or concomitant malignancy of any other type that could affect compliance with the protocol or interpretation of results. Patients with curatively treated basal cell carcinoma of the skin or in situ cervix cancer are generally eligible.
* Pre-existing motor or sensory neuropathy of grade \> 1 for any reason
* Patients with a history of hypersensitivity due to drugs containing polyoxyethylene castor oil (Cremophor EL) (e.g., ciclosporin), or hardened castor oil (e.g., vitamin preparations for injection, etc.)
* Other serious illness or medical condition including: history of documented congestive cardiac failure; angina pectoris requiring anti-anginal medication; evidence of transmural infarction on ECG; poorly controlled hypertension (e.g. systolic \>180 mm Hg or diastolic \>100 mm Hg; however, patients with hypertension which is well controlled on medication are eligible); clinically significant valvular heart disease; high-risk uncontrolled arrhythmias
* Patients with a history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant and precluding informed consent or adversely affecting compliance with study drugs
* Serious uncontrolled infections (bacterial or viral) or poorly controlled diabetes mellitus
* Hematology and biochemistry tests within normla limits
* Baseline left ventricular ejection fraction (LVEF) \< 50% by echocardiography or multi-gated scintigraphic scan (MUGA)

Primary outcomes:
measure: pathologic Complete Response (pCR)
timeFrame: At the time of surgery: 40 months after the randomization of the first patient
Secondary outcomes:
measure: clinical Overall Response (cOR)
timeFrame: At the time of surgery: 40 months after the randomization of the first patient
measure: Event Free Survival (EFS)
timeFrame: 5 years after the first patient in and 10 years after randomization of last patient in
measure: Distant Event Free Survival (DEFS)
timeFrame: 5 years after the first patient in and 10 years after randomization of last patient in
measure: Local Event Free Survival
timeFrame: 5 years after the first patient in and 10 years after randomization of last patient in
measure: Regional Event Free Survival
timeFrame: 5 years after the first patient in and 10 years after randomization of last patient in
measure: Overall Survival (OS)
timeFrame: 13 years from the date of first patient in
measure: Safety and Tolerability
timeFrame: Each participant will be followed for the duration of treatment period, approximately 9 months
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: East Melbourne
country: Australia
facility: Peter McCallum Cancer Centre
state: Victoria
city: East Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre Department of Surgical Oncology
state: Victoria
city: Ringwood East
country: Australia
facility: Eastern Health Breast Cancer Research - Maroondah Breast Clinic
state: Victoria
city: Ringwood East
country: Australia
facility: Eastern Health Breast Cancer Research Maroondah Breast Clinic
state: Victoria
city: Perth
country: Australia
facility: Mount Hospital - Breast Clinical Trials Unit
state: Western Australia
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Augsburg
country: Germany
facility: Klinikum Augsburg International Patient Service
city: Berlin
country: Germany
facility: Frauenarzt-Zentrum-Zehlendorf
city: Bochum
country: Germany
facility: Augusta-Kranken-Anstalt gGmbH Klinik für Hämatologie, Onkologie & Palliativmedizin
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen - Frauenklinik - Poliklinik
city: Frankfurt
country: Germany
facility: Agaplesion Markus Hospital - Frankfurt
city: Frankfurt
country: Germany
facility: Bethanien-Krankenhaus Onkologisches Zentrum
city: Hamburg
country: Germany
facility: Mammazentrum - Hamburg am Krankenhaus Jerusalem
city: Hannover
country: Germany
facility: Gynäkologisch-Onkologische Praxis
city: Köln
country: Germany
facility: St.Elisabeth-Krankenhaus Brustzentrum
city: Munich
country: Germany
facility: Interdisciplinary Oncology Center
city: Munich
country: Germany
facility: Praxis Gynäkologie Arabella
city: Speyer
country: Germany
facility: Onkologische Schwerpunktpraxis
city: Bergamo
country: Italy
facility: Cliniche Gavazzeni - Humanitas Gavazzeni
state: BG
city: Bologna
country: Italy
facility: Policlinico Sant'Orsola Malpighi
state: BO
city: Cona
country: Italy
facility: Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant'Anna
state: Ferrara
city: Genova
country: Italy
facility: IST San Martino
state: GE
city: Monza
country: Italy
facility: A.O. San Gerardo
state: MB
city: Legnano
country: Italy
facility: A.O. Ospedale Civile di Legnano
state: MI
city: Milano
country: Italy
facility: Ospedale San Raffaele
state: MI
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto nazionale dei tumori
state: MI
city: Milano
country: Italy
facility: A.O. Ospedale Luigi Sacco
state: MI
city: Milano
country: Italy
facility: A.O. Ospedale Niguarda Ca' Granda
state: MI
city: Camposampiero
country: Italy
facility: ULSS 15 Alta Padovana
state: PD
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
state: PV
city: Reggio Emilia
country: Italy
facility: Arcispedale Santa Maria Nuova
state: RE
city: Udine
country: Italy
facility: Ospedale Santa Maria della Misericordia
state: UD
city: Vicenza
country: Italy
facility: Azienda ULSS 6 di Vicenza
state: VI
city: St. Petersburg
country: Russian Federation
facility: NN Petrov Research Institute of Oncology
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
city: Zaragoza
country: Spain
facility: Hospital Clinico Lozano Blesa
state: Aragon
city: Zaragoza
country: Spain
facility: Miguel Servet University Hospital
state: Aragon
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llàtzer Palma de Mallorca
state: Baleares
city: Sabadell
country: Spain
facility: Corporacio Sanitaria Parc Tauli
state: Barcelona
city: Terrassa
country: Spain
facility: Consorci Sanitari de Terrassa
state: Barcelona
city: Alcorcón
country: Spain
facility: Hospital Universitario Fundacion Alcorcón
state: Madrid
city: La Laguna
country: Spain
facility: Hospital Universitario de Canarias
state: Tenerife
city: A Coruña
country: Spain
facility: Centro Oncologico de Galicia
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Badalona
country: Spain
facility: Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Clinic i Provencial
city: Caceres
country: Spain
facility: Hospital San Pedro de Alcantara
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Donostia
country: Spain
facility: Onkologikoa
city: Jaen
country: Spain
facility: Complejo Hospitalario de Jaen
city: La Coruna
country: Spain
facility: Hospital Teresa Herrera (Chuac)
city: Lleida
country: Spain
facility: Hospital Universitari Arnau de Vilanove de Lleida
city: Madrid
country: Spain
facility: Gregorio Maraňón Hospital
city: Madrid
country: Spain
facility: Hospital La Paz
city: Madrid
country: Spain
facility: MD Anderson Cancer Center Madrid
city: Murcia
country: Spain
facility: J.M. Morales Meseguer, Universitary Hospital Marques in los Velez
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
city: San Sebastián
country: Spain
facility: Hospital Universitario Donostia
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocio
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Toledo
country: Spain
facility: Hospital Virgen de la Salud
city: Valencia
country: Spain
facility: Instituto Valenciano Oncologia
city: Valencia
country: Spain
facility: Hospital Clinico Universita Valencia
city: Ávila
country: Spain
facility: Hospital Nuestra Señora de Sonsoles
Study officials:
affiliation: San Raffaele Hospital, Milan
name: Luca Gianni, MD
role: STUDY_CHAIR
References:
citation: Gianni L, Mansutti M, Anton A, Calvo L, Bisagni G, Bermejo B, Semiglazov V, Thill M, Chacon JI, Chan A, Morales S, Alvarez I, Plazaola A, Zambetti M, Redfern AD, Dittrich C, Dent RA, Magazzu D, De Fato R, Valagussa P, Tusquets I. Comparing Neoadjuvant Nab-paclitaxel vs Paclitaxel Both Followed by Anthracycline Regimens in Women With ERBB2/HER2-Negative Breast Cancer-The Evaluating Treatment With Neoadjuvant Abraxane (ETNA) Trial: A Randomized Phase 3 Clinical Trial. JAMA Oncol. 2018 Mar 1;4(3):302-308. doi: 10.1001/jamaoncol.2017.4612.