Neoadjuvant Chemotherapy With Nab-paclitaxel in Women With HER2-negative High-risk Breast Cancer

NCT ID: NCT01822314

Last Updated: 2024-03-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 632 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-30
• Study Completion Date: 2023-03-31

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

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Paclitaxel

Paclitaxel will be given on week 1, 2 and 3 followed by 1 week rest and will be repeated for 4 cycles.

AC or EC or FEC will then be given on day 1 every 3 weeks for 4 cycles

Group Type: ACTIVE_COMPARATOR

Paclitaxel

Intervention Type: DRUG

Paclitaxel at the dosage of 90 mg/m2 diluted in 250 mL of water for injection (WFI) over 1 hour given week 1, 2 and 3 followed by 1 week rest and will be repeated for 4 cycles followed by AC or EC (adriamycin or epirubicin and cyclophosphamide) on day 1 every 3 weeks for 4 cycles or FEC (fluorouracil, epirubicin, and cyclophosphamide) on day 1 every three weeks for 4 cycles

Abraxane

Abraxane will be given at the dosage of 125 mg/m2 on week 1, 2 and 3 followed by 1 week rest and will be repeated for 4 cycles.

AC or EC or FEC will then be given on day 1 every 3 weeks for 4 cycles

Group Type: EXPERIMENTAL

Abraxane

Intervention Type: DRUG

Abraxane at the dosage of 125 mg/m2 will be delivered over 30 minutes on week 1, 2 and 3 followed by 1 week rest. week rest and will be repeated for 4 cycles followed by AC or EC (adriamycin or epirubicin and cyclophosphamide) on day 1 every 3 weeks for 4 cycles or FEC (fluorouracil, epirubicin, and cyclophosphamide) on day 1 every three weeks for 4 cycles

Interventions

Abraxane

Abraxane at the dosage of 125 mg/m2 will be delivered over 30 minutes on week 1, 2 and 3 followed by 1 week rest. week rest and will be repeated for 4 cycles followed by AC or EC (adriamycin or epirubicin and cyclophosphamide) on day 1 every 3 weeks for 4 cycles or FEC (fluorouracil, epirubicin, and cyclophosphamide) on day 1 every three weeks for 4 cycles

Intervention Type: DRUG

Paclitaxel

Paclitaxel at the dosage of 90 mg/m2 diluted in 250 mL of water for injection (WFI) over 1 hour given week 1, 2 and 3 followed by 1 week rest and will be repeated for 4 cycles followed by AC or EC (adriamycin or epirubicin and cyclophosphamide) on day 1 every 3 weeks for 4 cycles or FEC (fluorouracil, epirubicin, and cyclophosphamide) on day 1 every three weeks for 4 cycles

Intervention Type: DRUG

Other Intervention Names

Nab-paclitaxel; No specific brand name

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Fondazione Michelangelo

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Luca Gianni, MD

Role: STUDY_CHAIR

San Raffaele Hospital, Milan

Locations

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Peter McCallum Cancer Centre

East Melbourne, Victoria, Australia

Peter MacCallum Cancer Centre Department of Surgical Oncology

East Melbourne, Victoria, Australia

Eastern Health Breast Cancer Research - Maroondah Breast Clinic

Ringwood East, Victoria, Australia

Eastern Health Breast Cancer Research Maroondah Breast Clinic

Ringwood East, Victoria, Australia

Mount Hospital - Breast Clinical Trials Unit

Perth, Western Australia, Australia

Royal Perth Hospital

Perth, Western Australia, Australia

Klinikum Augsburg International Patient Service

Augsburg, , Germany

Frauenarzt-Zentrum-Zehlendorf

Berlin, , Germany

Augusta-Kranken-Anstalt gGmbH Klinik für Hämatologie, Onkologie & Palliativmedizin

Bochum, , Germany

St.Elisabeth-Krankenhaus Brustzentrum

Cologne, , Germany

Universitätsklinikum Erlangen - Frauenklinik - Poliklinik

Erlangen, , Germany

Agaplesion Markus Hospital - Frankfurt

Frankfurt, , Germany

Bethanien-Krankenhaus Onkologisches Zentrum

Frankfurt, , Germany

Mammazentrum - Hamburg am Krankenhaus Jerusalem

Hamburg, , Germany

Gynäkologisch-Onkologische Praxis

Hanover, , Germany

Interdisciplinary Oncology Center

Munich, , Germany

Praxis Gynäkologie Arabella

Munich, , Germany

Onkologische Schwerpunktpraxis

Speyer, , Germany

Cliniche Gavazzeni - Humanitas Gavazzeni

Bergamo, BG, Italy

Policlinico Sant'Orsola Malpighi

Bologna, BO, Italy

Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant'Anna

Cona, Ferrara, Italy

IST San Martino

Genova, GE, Italy

A.O. San Gerardo

Monza, MB, Italy

A.O. Ospedale Civile di Legnano

Legnano, MI, Italy

Ospedale San Raffaele

Milan, MI, Italy

Fondazione IRCCS Istituto nazionale dei tumori

Milan, MI, Italy

A.O. Ospedale Luigi Sacco

Milan, MI, Italy

A.O. Ospedale Niguarda Ca' Granda

Milan, MI, Italy

ULSS 15 Alta Padovana

Camposampiero, PD, Italy

Fondazione IRCCS Policlinico San Matteo

Pavia, PV, Italy

Arcispedale Santa Maria Nuova

Reggio Emilia, RE, Italy

Ospedale Santa Maria della Misericordia

Udine, UD, Italy

Azienda ULSS 6 di Vicenza

Vicenza, VI, Italy

NN Petrov Research Institute of Oncology

Saint Petersburg, , Russia

National Cancer Centre Singapore

Singapore, , Singapore

Hospital Clinico Lozano Blesa

Zaragoza, Aragon, Spain

Miguel Servet University Hospital

Zaragoza, Aragon, Spain

Hospital Son Llàtzer Palma de Mallorca

Palma de Mallorca, Balearic Islands, Spain

Corporacio Sanitaria Parc Tauli

Sabadell, Barcelona, Spain

Consorci Sanitari de Terrassa

Terrassa, Barcelona, Spain

Hospital Universitario Fundacion Alcorcón

Alcorcón, Madrid, Spain

Hospital Universitario de Canarias

San Cristóbal de La Laguna, Tenerife, Spain

Centro Oncologico de Galicia

A Coruña, , Spain

Hospital Teresa Herrera (Chuac)

A Coruña, , Spain

Hospital General Universitario de Alicante

Alicante, , Spain

Hospital Nuestra Señora de Sonsoles

Ávila, , Spain

Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol

Badalona, , Spain

Hospital del Mar

Barcelona, , Spain

Hospital Clinic i Provencial

Barcelona, , Spain

Hospital San Pedro de Alcantara

Cáceres, , Spain

Hospital Universitario Reina Sofía

Córdoba, , Spain

Onkologikoa

Donostia / San Sebastian, , Spain

Complejo Hospitalario de Jaen

Jaén, , Spain

Hospital Universitari Arnau de Vilanove de Lleida

Lleida, , Spain

Gregorio Maraňón Hospital

Madrid, , Spain

Hospital La Paz

Madrid, , Spain

MD Anderson Cancer Center Madrid

Madrid, , Spain

J.M. Morales Meseguer, Universitary Hospital Marques in los Velez

Murcia, , Spain

Hospital Clinico Universitario de Salamanca

Salamanca, , Spain

Hospital Universitario Donostia

San Sebastián, , Spain

Hospital Virgen del Rocio

Seville, , Spain

Hospital Universitario Virgen Macarena

Seville, , Spain

Hospital Virgen de la Salud

Toledo, , Spain

Instituto Valenciano Oncologia

Valencia, , Spain

Hospital Clinico Universita Valencia

Valencia, , Spain

Countries

Australia; Germany; Italy; Russia; Singapore; Spain

References

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.

Reference Type: DERIVED

PMID: 29327055 (View on PubMed)

Other Identifiers

2012-003481-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

FM-12-B01

Identifier Type: -

Identifier Source: org_study_id