E7389 Versus Capecitabine in Patients With Locally Advanced or Metastatic Breast Cancer Previously Treated With Anthracyclines and Taxanes
A Phase III Open Label, Randomized Two-Parallel-Arm Multicenter Study of E7389 Versus Capecitabine in Patients With Locally Advanced or Metastatic Breast Cancer Previously Treated With Anthracyclines and Taxanes
1 other identifier
interventional
1,276
23 countries
169
Brief Summary
The purpose of this study is to compare E7389 versus capecitabine in patients with locally advanced or metastatic breast cancer who are refractory to the most recent chemotherapy. This is an open-label, randomized, two-parallel arm study. Patients will be randomized to receive either E7389 or capecitabine on a one-to-one ratio.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Sep 2006
Longer than P75 for phase_3
169 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 13, 2006
CompletedFirst Posted
Study publicly available on registry
June 15, 2006
CompletedStudy Start
First participant enrolled
September 20, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 12, 2012
CompletedResults Posted
Study results publicly available
September 30, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
December 11, 2017
CompletedJune 18, 2020
January 1, 2018
5.5 years
June 13, 2006
July 31, 2013
May 28, 2020
Conditions
Outcome Measures
Primary Outcomes (2)
Overall Survival (OS)
OS was measured from the date of randomization until the date of death from any cause, or the last date the participant was known to be alive. Participants who were lost to follow-up or who were alive at the date of data cutoff were censored. The censoring rules for OS were as follows: 1) if the participant was still alive at data cutoff, the date of data cutoff was considered the end date, and 2) if the participant was lost to follow-up before data cutoff, the date they were last known to be alive was considered the end date. Participants who survived past the end of the study were counted as in the full study period. If death occurred after data cutoff, the end date was to be censored at the time of data cutoff.
From date of randomization until date of death from any cause, assessed up to data cutoff date of 12 Mar 2012, or up to approximately 6 years
Progression Free Survival (PFS)
PFS was defined as the time (in days) from the date of randomization to the date of the first sign of disease progression based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 (v 1.1) or date of death, regardless of cause. Disease progression was measured by computed tomography (CT) and magnetic resonance imaging (MRI) performed on lesions targeted at baseline for tumor assessment. Disease progression (as assessed by independent review of the imaging scans) per RECIST v 1.1 was defined as at least a 20% increase in the sum of the diameters of the target lesions (taking as reference the smallest sum on study, including the baseline sum if that is the smallest), and an absolute increase of at least 5 millimeter (mm). Note that the appearance of one or more new lesions was also considered as disease progression.
From date of randomization to the date of disease progression or death (whichever occurred first), assessed up to data cutoff date of 12 Mar 2012 or up to approximately 6 years
Secondary Outcomes (12)
Change From Baseline in Global Health Status/Quality of Life (QoL) Measured by European Organization for the Treatment of Cancer Quality of Life Core Questionnaire Scores Based on Core 30 Items (EORTC-QLQ-C30) at Week 6
Baseline and Week 6
Change From Baseline in European Organization for the Treatment of Cancer Quality of Life Core Questionnaire Scores Based on Breast Cancer Specific 23 Items (EORTC-QLQ- BR 23) at Week 6
Baseline and Week 6
Objective Response Rate (ORR): Independent Review
From date of randomization until date of first documentation of CR or PR, assessed up to data cutoff date of 12 Mar 2012 or up to approximately 6 years
Duration of Response (DOR): Independent Review
From first documented CR or PR until date of recurrent or progressive disease or death, assessed up to data cutoff of date of 12 Mar 2012 or up to approximately 6 years
Overall Survival Rate
From the date of randomization to Year 1, 2 and 3
- +7 more secondary outcomes
Study Arms (2)
1
EXPERIMENTAL2
ACTIVE COMPARATORInterventions
1.4 mg/m\^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days
Capecitabine 2.5 g/m\^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days
Eligibility Criteria
You may qualify if:
- Female patients with histologically or cytologically confirmed carcinoma of the breast. Every effort should be made to ensure that paraffin embedded tissue or slides from the diagnostic biopsy or surgical specimen are available for confirmation of diagnosis.
- Patients with locally advanced or metastatic disease who have received up to three prior chemotherapy regimens, and no more than two prior regimens for advanced and/or metastatic disease.
- Regimens must have included an anthracycline (e.g., doxorubicin, epirubicin) and a taxane (e.g., paclitaxel, docetaxel), either in combination or in separate regimens.
- Patients with known human epidermal growth factor 2 (HER2/neu) over-expressing tumors may additionally have been treated with trastuzumab in centers where this treatment is available.
- Patients with known estrogen and/or progesterone receptor-expressing tumors may have additionally been treated with hormonal therapy.
- Resolution of all chemotherapy or radiation-related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy \<= Grade 2 and alopecia.
- Age \>= 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
- Life expectancy of \>= 3 months.
- Adequate renal function as evidenced by serum creatinine \<1.5 mg/dL or calculated creatinine clearance \> 50 mL/minute (min) per the Cockcroft and Gault formula.
- Adequate bone marrow function as evidenced by absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L, hemoglobin \>= 10.0 g/dL (a hemoglobin \< 10.0 g/dL acceptable if it is corrected by growth factor or transfusion), and platelet count \>= 100 x 10\^9/L.
- Adequate liver function as evidenced by bilirubin \<= 1.5 times the upper limits of normal (ULN) and alkaline phosphatase, alanine transaminase (ALT), and aspartate transaminase (AST) \<= 3 x ULN (in the case of liver metastases \<= 5 x ULN), or in case of bone metastases, liver specific alkaline phosphatase \<= 3 x ULN.
- Patients willing and able to complete the EORTC (European Organization for Research on the Treatment of Cancer) quality of life questionnaire (QLQ-C30 with breast cancer module QLQ-BR23) and to record their pain level on the Visual Analog Scale (VAS).
- Patients willing and able to comply with the study protocol for the duration of the study.
- Written informed consent prior to any study-specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice.
You may not qualify if:
- Patients who have received more than three prior chemotherapy regimens for their disease, including adjuvant therapies, or patients who have received more than two prior chemotherapy regimens for advanced disease (other therapies are allowed e.g., anti-estrogens, trastuzumab and radiotherapy).
- Patients who have received capecitabine as a prior therapy for their disease.
- Patients who have received chemotherapy, radiation, or biological therapy within two weeks, or hormonal therapy, within one week before study treatment start, or any investigational drug within four weeks before study treatment start.
- Radiation therapy encompassing \> 30% of marrow.
- Prior treatment with mitomycin C or nitrosourea.
- Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen.
- Patients with brain or subdural metastases are not eligible, unless they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment with study treatment. Any symptoms attributed to brain metastases must be stable for at least 4 weeks before starting study treatment; radiographic stability should be determined by comparing a contrast-enhanced Computed Tomography Scan (CT) or Magnetic Resonance Imaging (MRI) brain scan performed during screening to a prior scan performed at least 4 weeks earlier.
- Patients with meningeal carcinomatosis.
- Patients who are receiving anti-coagulant therapy with warfarin or related compounds, other than for line patency, and cannot be changed to heparin-based therapy, are not eligible. If a patient is to continue on mini-dose warfarin, then the prothrombin time (PT)/international normalized ratio (INR) must be closely monitored.
- Women who are pregnant or breast-feeding; women of childbearing potential with either a positive pregnancy test at screening or no pregnancy test; women of childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception (considered to be two methods of contraception, one of which must be a barrier method, e.g. condom, diaphragm or cervical cap). Perimenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
- Severe/uncontrolled intercurrent illness/infection.
- Significant cardiovascular impairment (history of congestive heart failure \> New York Heart Association \[NYHA\] Grade II, unstable angina or myocardial infarction within the past six months, or serious cardiac arrhythmia).
- Patients with organ allografts requiring immunosuppression.
- Patients with known positive human immunodeficiency virus (HIV) status.
- Patients who have had a prior malignancy, other than carcinoma in situ of the cervix, or non-melanoma skin cancer, unless the prior malignancy was diagnosed and definitively treated \>= 5 years previously with no subsequent evidence of recurrence.
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Eisai Inc.lead
Study Sites (169)
Unknown Facility
Anaheim, California, United States
Unknown Facility
La Verne, California, United States
Unknown Facility
Poway, California, United States
Unknown Facility
Centralia, Illinois, United States
Unknown Facility
Augusta, Maine, United States
Unknown Facility
Boston, Massachusetts, United States
Unknown Facility
Jefferson City, Missouri, United States
Unknown Facility
Lebanon, New Hampshire, United States
Unknown Facility
Ephrata, Pennsylvania, United States
Unknown Facility
Cookeville, Tennessee, United States
Unknown Facility
Germantown, Tennessee, United States
Unknown Facility
Amarillo, Texas, United States
Unknown Facility
Wenatchee, Washington, United States
Hospital General de Agudos Teodoro Alvarez
Ciudad Autonoma, Buenos Aires, C1406FWY, Argentina
Instituto Argentino de Diagnostico y Tratamiento
Cuidad Autonoma de Buenos Aires, Buenos Aires, Argentina
Unknown Facility
La Plata, Buenos Aires, 1898, Argentina
Unknown Facility
La Plata, Buenos Aires, Argentina
Unknown Facility
Pilar, Buenos Aires, B1629AHJ, Argentina
Corporacion Medica General San Martin
San Martín, Buenos Aires, Argentina
Unknown Facility
Rosario, Santa Fe Province, S2000DSK, Argentina
Unknown Facility
San Miguel de Tucumán, Tucumán Province, T4000IAK, Argentina
Unknown Facility
Bahía Blanca, Bema 8000, Argentina
Unknown Facility
Buenos Aires, C1280AEB, Argentina
Hospital Italiano de Buenos Aires
Buenos Aires, Argentina
Unknown Facility
Buenos Aires, Argentina
Unknown Facility
Ciudad Autonoma, Argentina
Unknown Facility
Mendoza, Argentina
Unknown Facility
Santa Fe, S3000FFU, Argentina
Bankstown Hospital, Oncology Trials Unit
Bankstown, New South Wales, Australia
Unknown Facility
Hornsby, New South Wales, 2077, Australia
Liverpool Hospital, Cancer Therapy Centre
Liverpool, New South Wales, Australia
Ashford Cancer Centre
Adelaide, South Australia, 5035, Australia
Royal Hobart Hospital
Hobart, Tasmania, 7000, Australia
Saint Vincent's Hospital
Fitzroy, Victoria, 3065, Australia
Royal Perth Hospital
Perth, Western Australia, 6000, Australia
Epworth Freemasons Hospital
East Melbourne, Australia
Sir Charles Gairdner Hospital, Dept. of Medical Oncology
Nedlands, Australia
Mater Adult Hospital
South Brisbane, Australia
OLVZ Aalst, Oncology Service
Aalst, 9300, Belgium
Institut Jules Bordet, Medical Oncology Unit
Brussels, 1000, Belgium
Algemeen Ziekenhuis Sint Lucas
Ghent, 9000, Belgium
Centre Hosptialier Universitaire Sart Tilman Liege
Liège, Belgium
Unknown Facility
Florianópolis, Brazil
Associacao Hospital de Caridade Ijui
Ijuí, Brazil
Instituto de Oncologia Ltda
Jundiaí, Brazil
Proonco Centro de Tratamento Oncologico
Londrina, Brazil
Hospital de Clinicas de Porto Alegre, Servicio de Oncologia
Porto Alegre, Brazil
Hospital Nossa Senhora da Conceicao
Porto Alegre, Brazil
Servico de Quimioterapia de Pernambuco-SEQUIPE
Recife, Brazil
Instituto Ribeiraopretano de Combate ao Cancer
Ribeirão Preto, Brazil
Nucleo de Oncologia da Bahia
Salvador, Brazil
Faculdade de Medicina do ABC
Santo André, Brazil
Grupo Paulista de Oncologia Integrada Ltda
São Paulo, Brazil
Hospital das Clinicas de Faculdade de Medicina da Universidade de Sao
São Paulo, Brazil
Hospital do Cancer de Sao Paulo-AC Camargo
São Paulo, Brazil
Hospital do Cancer de Sao Paulo-AC. Camargo
São Paulo, Brazil
Instituto Brasileiro de Controle do Cancer-IBCC
São Paulo, Brazil
Unknown Facility
Burgas, Bulgaria
Unknown Facility
Gabrovo, Bulgaria
Unknown Facility
Pleven, Bulgaria
Unknown Facility
Plovdiv, Bulgaria
Unknown Facility
Rousse, Bulgaria
Unknown Facility
Shumen, Bulgaria
Unknown Facility
Sofia, Bulgaria
Unknown Facility
Stara Zagora, Bulgaria
Unknown Facility
Varna, Bulgaria
Unknown Facility
Kingston, Ontario, Canada
Montreal General Hospital
Montreal, Quebec, H3G 1A4, Canada
Hopital du Sacre-Coeur de Montreal
Montreal, Quebec, H4J 1C5, Canada
Centre Hospitalier Universitaire de Montreal, Hopital Notre Dame
Montreal, Canada
Thunder Bay Regional Health Science Centre Northwestern Ontario
Thunder Bay, Canada
Nemocnice Ceske Budejovice, a.s.
České Budějovice, Czechia
Onkologicka Klinika, Fakutni Nemocnice
Olomouc, Czechia
1. LF UK, Ustav radiacnej onkologie
Prague, Czechia
Krajska nemocnice T. Bati
Zlin Poiters, Czechia
Centre Hospitalier La Roche sur Yon, CHD les Oudairies
La Roche-sur-Yon, France
CHU de Poitiers, Service d'Oncologie Medicale
Poitiers, France
Hopital Nord Saint-Etienne
Saint-Priest-en-Jarez, France
Augusta-Kranken-Anstalt, Klinik fur Hamatologie und Onkologie
Bochum, Germany
Unknown Facility
Hamburg, Germany
Unknown Facility
Homburg, Germany
Universitatsfrauenklinik Magdeburg
Magdeburg, Germany
Unknown Facility
Rostock, Germany
Unknown Facility
Pátrai, Greece
Unknown Facility
Gyor, Budapest, Hungary
Debrecen University
Debrecen, Hungary
Unknown Facility
Debrecen, Hungary
Unknown Facility
Gyula, 5700, Hungary
Pecsi Tudomanyegyetem, Onkoterapias Intezet
Pécs, Hungary
Unknown Facility
Szeged, Hungary
Unknown Facility
Veszprém, Hungary
Barzilai Medical Center
Ashkelon, Israel
Soroka Medical Center
Beersheba, Israel
Sharet Institute of Oncology
Jerusalem, Israel
Meir Hospital, Sapir Medical Center
Kfar Saba, Israel
Rabin Medical Center
Petah Tikva, Israel
Kaplan Medical Center
Rehovot, Israel
The Chaim Sheba Medical Center
Tel Litwinsky, Israel
Unknown Facility
Ancona, Italy
Unita Operativa de Oncologia
Lugo, Italy
Unknown Facility
Meldola, Italy
Unknown Facility
Modena, Italy
Azienda Ospedaliera San Salvatore
Pesaro, Italy
Ospedale Civile S. Maria delle Croci
Ravenna, Italy
UO di Onco-ematologia
Rimini, Italy
Unknown Facility
Sassari, Italy
Centro Estatal de Cancerologia
Chihuahua City, Mexico
Unknown Facility
Monterrey, Mexico
Consultorio del Dr. Trigueros
Morelia, Mexico
Regionalny Osrodek Onkologii
Bialystok, Poland
Unknown Facility
Bytom, Poland
Unknown Facility
Elblag, Poland
Wojewodzkie Centrum Onkologii
Gdansk, 80-210, Poland
Unknown Facility
Krakow, Poland
Unknown Facility
Olsztyn, 10-513, Poland
Unknown Facility
Rybnik, 44-200, Poland
Unknown Facility
Torun, Poland
Wojewodzki Szpital Specjalistyczny
Wroclaw, 51-124, Poland
Unknown Facility
Cluj-Napoca, Cluj, 400015, Romania
Spitalul Militar Central Bucuresti
Bucharest, 10825, Romania
Unknown Facility
Bucharest, Romania
Unknown Facility
Cluj-Napoca, Romania
Centrul de Oncologie Medicala
Iași, 700106, Romania
Spitalul Clinic Judetean Sibiu
Sibiu, Romania
Unknown Facility
Timișoara, Romania
Regional Oncology Dispensary
Yaroslavl, Yaroslavlr, 150054, Russia
Unknown Facility
Barnaul, Russia
Unknown Facility
Kazan', Russia
Unknown Facility
Kirov, Russia
Unknown Facility
Krasnodar, Russia
Blokhin Cancer Research Centre
Moscow, 115478, Russia
Unknown Facility
Moscow, Russia
Unknown Facility
Nizhny Novgorod, Russia
Unknown Facility
Obninsk, Russia
Unknown Facility
Rostov-on-Don, Russia
Unknown Facility
Saint Petersburg, Russia
Unknown Facility
Saratov, Russia
Unknown Facility
Sochi, Russia
Unknown Facility
Tomsk, Russia
Unknown Facility
Vladimir, Russia
Unknown Facility
Singapore, Singapore
Unknown Facility
Mayville, Durban, 4091, South Africa
Unknown Facility
Pretoria, Gaunteng, South Africa
Unknown Facility
Groenkloof, Pretoria, South Africa
Panorama Medical Centre
Cape Town, South Africa
Unknown Facility
Durban, 4091, South Africa
Unknown Facility
Johannesburg, South Africa
Unknown Facility
Sandton, 2199, South Africa
Unknown Facility
Barakaldo, Vizcaya, Spain
Unknown Facility
A Coruña, Spain
Unknown Facility
Barcelona, Spain
Unknown Facility
Guadalajara, Spain
Unknown Facility
Seville, Spain
Unknown Facility
Valencia, Spain
Unknown Facility
Changhua, Taiwan
Unknown Facility
Taichung, Taiwan
Unknown Facility
Tainan, Taiwan
Unknown Facility
Taipei, Taiwan
Unknown Facility
Yung-Kang City, Taiwan
Unknown Facility
Chernihiv, Ukraine
Unknown Facility
Dnipro, Ukraine
Unknown Facility
Donetsk, Ukraine
Unknown Facility
Kharkiv, Ukraine
Unknown Facility
Khmelnytskyi, Ukraine
Unknown Facility
Kiev, Ukraine
Unknown Facility
Kryvyi Rih, Ukraine
Unknown Facility
Kyiv, Ukraine
Unknown Facility
Lviv, Ukraine
Unknown Facility
Odesa, Ukraine
Related Publications (5)
Twelves C, Awada A, Cortes J, Yelle L, Velikova G, Olivo MS, Song J, Dutcus CE, Kaufman PA. Subgroup Analyses from a Phase 3, Open-Label, Randomized Study of Eribulin Mesylate Versus Capecitabine in Pretreated Patients with Advanced or Metastatic Breast Cancer. Breast Cancer (Auckl). 2016 Jun 28;10:77-84. doi: 10.4137/BCBCR.S39615. eCollection 2016.
PMID: 27398025DERIVEDTwelves C, Cortes J, Kaufman PA, Yelle L, Awada A, Binder TA, Olivo M, Song J, O'Shaughnessy JA, Jove M, Perez EA. "New" metastases are associated with a poorer prognosis than growth of pre-existing metastases in patients with metastatic breast cancer treated with chemotherapy. Breast Cancer Res. 2015 Dec 9;17(1):150. doi: 10.1186/s13058-015-0657-1.
PMID: 27391598DERIVEDCortes J, Hudgens S, Twelves C, Perez EA, Awada A, Yelle L, McCutcheon S, Kaufman PA, Forsythe A, Velikova G. Health-related quality of life in patients with locally advanced or metastatic breast cancer treated with eribulin mesylate or capecitabine in an open-label randomized phase 3 trial. Breast Cancer Res Treat. 2015 Dec;154(3):509-20. doi: 10.1007/s10549-015-3633-7. Epub 2015 Nov 14.
PMID: 26567010DERIVEDKaufman PA, Awada A, Twelves C, Yelle L, Perez EA, Velikova G, Olivo MS, He Y, Dutcus CE, Cortes J. Phase III open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2015 Feb 20;33(6):594-601. doi: 10.1200/JCO.2013.52.4892. Epub 2015 Jan 20.
PMID: 25605862DERIVEDTwelves C, Cortes J, Vahdat LT, Wanders J, Akerele C, Kaufman PA. Phase III trials of eribulin mesylate (E7389) in extensively pretreated patients with locally recurrent or metastatic breast cancer. Clin Breast Cancer. 2010 Apr;10(2):160-3. doi: 10.3816/CBC.2010.n.023.
PMID: 20299316DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Eisai Medical Information
- Organization
- Eisai Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 13, 2006
First Posted
June 15, 2006
Study Start
September 20, 2006
Primary Completion
March 12, 2012
Study Completion
December 11, 2017
Last Updated
June 18, 2020
Results First Posted
September 30, 2013
Record last verified: 2018-01