Metastatic Breast CancerPhase 3NCT00337103
E7389 Versus Capecitabine in Patients With Locally Advanced or Metastatic Breast Cancer Previously Treated With Anthracyclines and Taxanes
A Phase 3 study testing Eribulin Mesylate and Capecitabine in people with Metastatic Breast Cancer, run by Eisai Inc. at 169 sites in 23 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- Eribulin Mesylate and Capecitabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,276 participants
- Where
- 169 sitesin 23 countries
- Study dates
- 20 Sep 2006to 11 Dec 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
- Patients with pre-existing neuropathy > Grade 2.
- Patients with a hypersensitivity to halichondrin B and/or halichondrin B chemical derivative.
- Patients who participated in a prior E7389 clinical trial.
- Patients with other significant disease or disorders that, in the Investigator's opinion, would exclude the patient from the study.
Trial locations and contacts
169 sites in 23 countries.
169 sites in 23 countries
Argentina15 sites
Study site
Bahía Blanca, Bema 8000
Study site
Buenos Aires, C1280AEB
Hospital Italiano de Buenos Aires
Buenos Aires
Study site
Buenos Aires
Hospital General de Agudos Teodoro Alvarez
Ciudad Autonoma, Buenos Aires, C1406FWY
Study site
Ciudad Autonoma
Instituto Argentino de Diagnostico y Tratamiento
Cuidad Autonoma de Buenos Aires, Buenos Aires
Study site
La Plata, Buenos Aires, 1898
Study site
La Plata, Buenos Aires
Study site
Mendoza
Study site
Pilar, Buenos Aires, B1629AHJ
Study site
Rosario, Santa Fe Province, S2000DSK
Corporacion Medica General San Martin
San Martín, Buenos Aires
Study site
San Miguel de Tucumán, Tucumán Province, T4000IAK
Study site
Santa Fe, S3000FFU
Brazil15 sites
Study site
Florianópolis
Associacao Hospital de Caridade Ijui
Ijuí
Instituto de Oncologia Ltda
Jundiaí
Proonco Centro de Tratamento Oncologico
Londrina
Hospital de Clinicas de Porto Alegre, Servicio de Oncologia
Porto Alegre
Hospital Nossa Senhora da Conceicao
Porto Alegre
Servico de Quimioterapia de Pernambuco-SEQUIPE
Recife
Instituto Ribeiraopretano de Combate ao Cancer
Ribeirão Preto
Nucleo de Oncologia da Bahia
Salvador
Faculdade de Medicina do ABC
Santo André
Grupo Paulista de Oncologia Integrada Ltda
São Paulo
Hospital das Clinicas de Faculdade de Medicina da Universidade de Sao
São Paulo
Hospital do Cancer de Sao Paulo-AC Camargo
São Paulo
Hospital do Cancer de Sao Paulo-AC. Camargo
São Paulo
Instituto Brasileiro de Controle do Cancer-IBCC
São Paulo
Russia15 sites
Study site
Barnaul
Study site
Kazan'
Study site
Kirov
Study site
Krasnodar
Blokhin Cancer Research Centre
Moscow, 115478
Study site
Moscow
Study site
Nizhny Novgorod
Study site
Obninsk
Study site
Rostov-on-Don
Study site
Saint Petersburg
Study site
Saratov
Study site
Sochi
Study site
Tomsk
Study site
Vladimir
Regional Oncology Dispensary
Yaroslavl, Yaroslavlr, 150054
United States13 sites
Study site
Amarillo, Texas
Study site
Anaheim, California
Study site
Augusta, Maine
Study site
Boston, Massachusetts
Study site
Centralia, Illinois
Study site
Cookeville, Tennessee
Study site
Ephrata, Pennsylvania
Study site
Germantown, Tennessee
Study site
Jefferson City, Missouri
Study site
La Verne, California
Study site
Lebanon, New Hampshire
Study site
Poway, California
Study site
Wenatchee, Washington
Australia10 sites
Ashford Cancer Centre
Adelaide, South Australia, 5035
Bankstown Hospital, Oncology Trials Unit
Bankstown, New South Wales
Epworth Freemasons Hospital
East Melbourne
Saint Vincent's Hospital
Fitzroy, Victoria, 3065
Royal Hobart Hospital
Hobart, Tasmania, 7000
Study site
Hornsby, New South Wales, 2077
Liverpool Hospital, Cancer Therapy Centre
Liverpool, New South Wales
Sir Charles Gairdner Hospital, Dept. of Medical Oncology
Nedlands
Royal Perth Hospital
Perth, Western Australia, 6000
Mater Adult Hospital
South Brisbane
Ukraine10 sites
Study site
Chernihiv
Study site
Dnipro
Study site
Donetsk
Study site
Kharkiv
Study site
Khmelnytskyi
Study site
Kiev
Study site
Kryvyi Rih
Study site
Kyiv
Study site
Lviv
Study site
Odesa
Bulgaria9 sites
Study site
Burgas
Study site
Gabrovo
Study site
Pleven
Study site
Plovdiv
Study site
Rousse
Study site
Shumen
Study site
Sofia
Study site
Stara Zagora
Study site
Varna
Poland9 sites
Regionalny Osrodek Onkologii
Bialystok
Study site
Bytom
Study site
Elblag
Wojewodzkie Centrum Onkologii
Gdansk, 80-210
Study site
Krakow
Study site
Olsztyn, 10-513
Study site
Rybnik, 44-200
Study site
Torun
Wojewodzki Szpital Specjalistyczny
Wroclaw, 51-124
Italy8 sites
Study site
Ancona
Unita Operativa de Oncologia
Lugo
Study site
Meldola
Study site
Modena
Azienda Ospedaliera San Salvatore
Pesaro
Ospedale Civile S. Maria delle Croci
Ravenna
UO di Onco-ematologia
Rimini
Study site
Sassari
Hungary7 sites
Debrecen University
Debrecen
Study site
Debrecen
Study site
Gyor, Budapest
Study site
Gyula, 5700
Pecsi Tudomanyegyetem, Onkoterapias Intezet
Pécs
Study site
Szeged
Study site
Veszprém
Israel7 sites
Barzilai Medical Center
Ashkelon
Soroka Medical Center
Beersheba
Sharet Institute of Oncology
Jerusalem
Meir Hospital, Sapir Medical Center
Kfar Saba
Rabin Medical Center
Petah Tikva
Kaplan Medical Center
Rehovot
The Chaim Sheba Medical Center
Tel HaShomer
Romania7 sites
Spitalul Militar Central Bucuresti
Bucharest, 10825
Study site
Bucharest
Study site
Cluj-Napoca, Cluj, 400015
Study site
Cluj-Napoca
Centrul de Oncologie Medicala
Iași, 700106
Spitalul Clinic Judetean Sibiu
Sibiu
Study site
Timișoara
South Africa7 sites
Panorama Medical Centre
Cape Town
Study site
Durban, 4091
Study site
Groenkloof, Pretoria
Study site
Johannesburg
Study site
Mayville, Durban, 4091
Study site
Pretoria, Gaunteng
Study site
Sandton, 2199
Spain6 sites
Study site
A Coruña
Study site
Barakaldo, Vizcaya
Study site
Barcelona
Study site
Guadalajara
Study site
Seville
Study site
Valencia
Canada5 sites
Study site
Kingston, Ontario
Montreal General Hospital
Montreal, Quebec, H3G 1A4
Hopital du Sacre-Coeur de Montreal
Montreal, Quebec, H4J 1C5
Centre Hospitalier Universitaire de Montreal, Hopital Notre Dame
Montreal
Thunder Bay Regional Health Science Centre Northwestern Ontario
Thunder Bay
Germany5 sites
Augusta-Kranken-Anstalt, Klinik fur Hamatologie und Onkologie
Bochum
Study site
Hamburg
Study site
Homburg
Universitatsfrauenklinik Magdeburg
Magdeburg
Study site
Rostock
Taiwan5 sites
Study site
Changhua
Study site
Taichung
Study site
Tainan
Study site
Taipei
Study site
Yung-Kang City
Belgium4 sites
OLVZ Aalst, Oncology Service
Aalst, 9300
Institut Jules Bordet, Medical Oncology Unit
Brussels, 1000
Algemeen Ziekenhuis Sint Lucas
Ghent, 9000
Centre Hosptialier Universitaire Sart Tilman Liege
Liège
Czechia4 sites
Nemocnice Ceske Budejovice, a.s.
České Budějovice
Onkologicka Klinika, Fakutni Nemocnice
Olomouc
1. LF UK, Ustav radiacnej onkologie
Prague
Krajska nemocnice T. Bati
Zlin Poiters
France3 sites
Centre Hospitalier La Roche sur Yon, CHD les Oudairies
La Roche-sur-Yon
CHU de Poitiers, Service d'Oncologie Medicale
Poitiers
Hopital Nord Saint-Etienne
Saint-Priest-en-Jarez
Mexico3 sites
Centro Estatal de Cancerologia
Chihuahua City
Study site
Monterrey
Consultorio del Dr. Trigueros
Morelia
About this study
Official title: 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
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.
- Conditions
- Metastatic Breast Cancer
- Being tested
- Eribulin Mesylate, Capecitabine
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Eribulin MesylateDrug
1.4 mg/m^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days
CapecitabineDrug
Capecitabine 2.5 g/m^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: Eribulin Mesylate |
| 2 | Active comparator | Not described Receives: Drug: Capecitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
EORTC-QLQ-C30:cancer-specific instrument with 30 questions to assess the participant QoL. First 28 questions used to evaluate 5 functional scales (physical, role, cognitive, emotional, social), 3 symptom scales (fatigue, nausea and vomiting, pain) and other single items(dyspnoea, appetite loss, insomnia, constipation, diarrhea, financial difficulties). Each of these 28 questions assessed on 4-point scale(1=not at all, 2=a little, 3=quite a bit, 4=very much); functional scales: higher score=better level of functioning; symptom scale: higher score=more severe symptoms; for single items: higher score= more severe problem. Last 2 questions used to evaluate global health status (GHS)/QoL. Each question was assessed on 7-point scale (1=very poor to 7=excellent). Scores averaged, transformed to 0-100 scale; higher score=better quality of life/better level of functioning.
Measured: 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
EORTC-QLQ-BR23:disease-specific module for breast cancer developed as a supplement for the EORTC-QLQ-C30 to assess quality of life of participants with breast cancer. The scores from 23 items of QLQ-BR23 included functional scales (body image, sexual functioning, sexual enjoyment, future perspective), symptom scales (systemic therapy side effects, breast symptoms, arm symptoms, upset by hair loss). Each item was rated on a scale of 1 to 4 to record level of intensity (1= not at all, 2= a little, 3= quite a bit, 4= very much) within each scales. Scores averaged and transformed to 0-100 scale. High score indicated high/better level of functioning/healthy functioning. Negative change from Baseline indicated deterioration in QOL and positive change from Baseline indicated an improvement in QOL.
Measured: Baseline and Week 6
Objective Response Rate (ORR): Independent Review
ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v 1.1). CR is defined as disappearance of all target legions and non-target lesions. All pathological lymph nodes (whether target and non-target), must have reduction in their short axis to less than 10 mm. PR is defined as at least 30% decrease in the sum of the long diameter LD (hereafter referred to as sum of LD) of all target lesions, as compared with Baseline summed LD.
Measured: 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
DOR was defined as the time from first documented CR or PR until disease progression or death from any cause for those participants with a confirmed PR or CR measured by RECIST v1.1. CR defined as disappearance of all target and non-target lesions. All pathological lymph nodes(whether target and non-target), must have reduction in their short axis to less than 10 mm. PR defined as at least 30% decrease in the sum of the long diameter LD (hereafter referred to as sum of LD) of all target lesions, as compared with Baseline summed LD.
Measured: 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
One-, two-, and three- year's survival rates were defined as the percentage of participants who were alive at one, two, and three years respectively, and estimated using the Kaplan-Meier method and Greenwood Formula.
Measured: From the date of randomization to Year 1, 2 and 3
Change From Baseline in Pain Intensity by Visual Analog Scale (VAS) Until 30 Days After the Last Dose of Study Drug
Pain intensity was measured by marking a single vertical line that crosses a 1-100 mm unmarked VAS scale. The left-end of the visual analog scale was labelled "least possible pain" and the right-end of the visual analog scale was labelled "worst possible pain". The pain rating ranged from 0 to 100, with a higher score indicating more pain. A negative change score indicated improvement.
Measured: First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months)
Number of Participants With Consumption of Analgesics During the Study
Participants took analgesics as concomitant pain medications which are defined as pain medications that (1) started before the first dose of study drug and were continuing at the time of the first dose of study drug, or (2) started on/after the day of the first dose of study drug up to 30 days after the last dose of study drug medication
Measured: First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months)
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
TEAEs included both SAEs as well as non-SAEs.
Measured: First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months)
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Parameter Values
Measured: First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months)
Number of Participants Who Took at Least One Concomitant Medication
Concomitant medications included medications that either (1) started before the first dose of study drug and were continuing at the time of the first dose of study drug, or (2) started on or after the first dose of study drug up to 30 days after the last dose of study drug.
Measured: First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months)
Duration of Eribulin Mesylate Exposure
Data have been reported per primary analysis completion stage and final analysis completion stage. After primary analysis completion (at cutoff date of 12 March 2012), only 10 participants were still receiving study treatment.
Measured: Up to approximately 6 years for primary analysis completion stage, Up to approximately 6 years 2 months for final analysis completion stage
Plasma Concentrations of Eribulin Mesylate
Measured: Cycle 1 Day 1: 5-10 minutes(min), 15-30 min, 30-60 min, 60-90 min, 2-4 hours(hrs), 4-8 hrs, 10-24 hrs, 48-72 hrs, 72-96 hrs, 96-120 hrs after the start of infusion of Eribulin mesylate (Duration of each cycle is 21 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2006 (estimated)
- Study start20 Sep 2006
- Primary completion12 Mar 2012
- Study completion11 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- More trials run by Eisai Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,276 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00337103
- Sponsor's protocol ID
- E7389-G000-301
- Status last verified
- Jan 2018
- First submitted
- 13 Jun 2006
- Last updated
- 18 Jun 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
Publications
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.
PubMed 27398025Twelves 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.
PubMed 27391598Cortes 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.
PubMed 26567010Kaufman 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.
PubMed 25605862Twelves 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.
PubMed 20299316
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00337103
- Acronym / sponsor ID
- E7389-G000-301
- Conditions
- Metastatic Breast Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,276 participants (actual)
- Lead sponsor
- Eisai Inc.Industry (pharma, biotech, devices)
- Study start
- 20 Sep 2006 (actual)
- Primary completion
- 12 Mar 2012 (actual)
- Study completion
- 11 Dec 2017 (actual)
- First posted
- 15 Jun 2006 (estimated)
- Results
- Posted 30 Sep 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Eribulin Mesylate |
| 2 | Active comparator | Drug: Capecitabine |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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.
- 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.
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Eribulin Mesylate1.4 mg/m^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days | Drug | 1 |
| CapecitabineCapecitabine 2.5 g/m^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days | Drug | 2 |
Primary outcome
Overall Survival (OS)
Time frame: 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
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.
Progression Free Survival (PFS)
Time frame: 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
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.
12 secondary outcomes
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
Time frame: 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
Time frame: Baseline and Week 6
Objective Response Rate (ORR): Independent Review
Time frame: 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
Time frame: 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
Time frame: From the date of randomization to Year 1, 2 and 3
Change From Baseline in Pain Intensity by Visual Analog Scale (VAS) Until 30 Days After the Last Dose of Study Drug
Time frame: First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months)
Number of Participants With Consumption of Analgesics During the Study
Time frame: First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months)
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months)
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Parameter Values
Time frame: First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months)
Number of Participants Who Took at Least One Concomitant Medication
Time frame: First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months)
Duration of Eribulin Mesylate Exposure
Time frame: Up to approximately 6 years for primary analysis completion stage, Up to approximately 6 years 2 months for final analysis completion stage
Plasma Concentrations of Eribulin Mesylate
Time frame: Cycle 1 Day 1: 5-10 minutes(min), 15-30 min, 30-60 min, 60-90 min, 2-4 hours(hrs), 4-8 hrs, 10-24 hrs, 48-72 hrs, 72-96 hrs, 96-120 hrs after the start of infusion of Eribulin mesylate (Duration of each cycle is 21 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27398025Twelves 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.
- Derived from this study: PubMed 27391598Twelves 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.
- Derived from this study: PubMed 26567010Cortes 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.
- Derived from this study: PubMed 25605862Kaufman 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.
- Derived from this study: PubMed 20299316Twelves 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
169 sites in 23 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Eribulin Mesylate and Capecitabine in people with Metastatic Breast Cancer, run by Eisai Inc. at 169 sites in 23 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 169 sites in Argentina, Brazil, Russia, United States, Australia and 18 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Sep 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (OS) (time frame: 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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00337103, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2020.