E7389 Versus Capecitabine in Patients With Locally Advanced or Metastatic Breast Cancer Previously Treated With Anthracyclines and Taxanes
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1
|
Drug: Eribulin Mesylate
1.4 mg/m^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days
|
| Active Comparator: 2
|
Drug: Capecitabine
Capecitabine 2.5 g/m^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days
|
Outcome Measures
Primary Outcome Measures
- Overall Survival (OS) [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) [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.
Secondary Outcome Measures
- 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]
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.
- 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]
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.
- 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]
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.
- 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]
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.
- Overall Survival Rate [From the date of randomization to Year 1, 2 and 3]
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.
- Change From Baseline in Pain Intensity by Visual Analog Scale (VAS) Until 30 Days After the Last Dose of Study Drug [First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months)]
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.
- Number of Participants With Consumption of Analgesics During the Study [First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months)]
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
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months)]
TEAEs included both SAEs as well as non-SAEs.
- Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Parameter Values [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 [First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months)]
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.
- Duration of Eribulin Mesylate Exposure [Up to approximately 6 years for primary analysis completion stage, Up to approximately 6 years 2 months for final analysis completion stage]
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.
- Plasma Concentrations of Eribulin Mesylate [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)]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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 109/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 109/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.
Exclusion Criteria:
-
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.
-
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Anaheim | California | United States | ||
| 2 | La Verne | California | United States | ||
| 3 | Poway | California | United States | ||
| 4 | Centralia | Illinois | United States | ||
| 5 | Augusta | Maine | United States | ||
| 6 | Boston | Massachusetts | United States | ||
| 7 | Jefferson City | Missouri | United States | ||
| 8 | Lebanon | New Hampshire | United States | ||
| 9 | Ephrata | Pennsylvania | United States | ||
| 10 | Cookeville | Tennessee | United States | ||
| 11 | Germantown | Tennessee | United States | ||
| 12 | Amarillo | Texas | United States | ||
| 13 | Wenatchee | Washington | United States | ||
| 14 | Hospital General de Agudos Teodoro Alvarez | Ciudad Autonoma | Buenos Aires | Argentina | C1406FWY |
| 15 | Instituto Argentino de Diagnostico y Tratamiento | Cuidad Autonoma de Buenos Aires | Buenos Aires | Argentina | |
| 16 | La Plata | Buenos Aires | Argentina | 1898 | |
| 17 | La Plata | Buenos Aires | Argentina | ||
| 18 | Pilar | Buenos Aires | Argentina | B1629AHJ | |
| 19 | Corporacion Medica General San Martin | San Martin | Buenos Aires | Argentina | |
| 20 | Rosario | Santa Fe | Argentina | S2000DSK | |
| 21 | San Miguel de Tucuman | Tucuman | Argentina | T4000IAK | |
| 22 | Bahia Blanca | Argentina | Bema 8000 | ||
| 23 | Buenos Aires | Argentina | C1280AEB | ||
| 24 | Buenos Aires | Argentina | |||
| 25 | Hospital Italiano de Buenos Aires | Ciudad Autonoma de Buenos Aires | Argentina | ||
| 26 | Ciudad Autonoma | Argentina | |||
| 27 | Mendoza | Argentina | |||
| 28 | Santa Fe | Argentina | S3000FFU | ||
| 29 | Bankstown Hospital, Oncology Trials Unit | Bankstown | New South Wales | Australia | |
| 30 | Hornsby | New South Wales | Australia | 2077 | |
| 31 | Liverpool Hospital, Cancer Therapy Centre | Liverpool | New South Wales | Australia | |
| 32 | Ashford Cancer Centre | Adelaide | South Australia | Australia | 5035 |
| 33 | Royal Hobart Hospital | Hobart | Tasmania | Australia | 7000 |
| 34 | Saint Vincent's Hospital | Fitzroy | Victoria | Australia | 3065 |
| 35 | Royal Perth Hospital | Perth | Western Australia | Australia | 6000 |
| 36 | Epworth Freemasons Hospital | East Melbourne | Australia | ||
| 37 | Sir Charles Gairdner Hospital, Dept. of Medical Oncology | Nedlands | Australia | ||
| 38 | Mater Adult Hospital | South Brisbane | Australia | ||
| 39 | OLVZ Aalst, Oncology Service | Aalst | Belgium | 9300 | |
| 40 | Institut Jules Bordet, Medical Oncology Unit | Brussels | Belgium | 1000 | |
| 41 | Algemeen Ziekenhuis Sint Lucas | Ghent | Belgium | 9000 | |
| 42 | Centre Hosptialier Universitaire Sart Tilman Liege | Liege | Belgium | ||
| 43 | Florianopolis | Brazil | |||
| 44 | Associacao Hospital de Caridade Ijui | Ijui | Brazil | ||
| 45 | Instituto de Oncologia Ltda | Jundiai | Brazil | ||
| 46 | Proonco Centro de Tratamento Oncologico | Londrina | Brazil | ||
| 47 | Hospital de Clinicas de Porto Alegre, Servicio de Oncologia | Porto Alegre | Brazil | ||
| 48 | Hospital Nossa Senhora da Conceicao | Porto Alegre | Brazil | ||
| 49 | Servico de Quimioterapia de Pernambuco-SEQUIPE | Recife | Brazil | ||
| 50 | Instituto Ribeiraopretano de Combate ao Cancer | Ribeirao Preto | Brazil | ||
| 51 | Nucleo de Oncologia da Bahia | Salvador | Brazil | ||
| 52 | Faculdade de Medicina do ABC | Santo Andre | Brazil | ||
| 53 | Grupo Paulista de Oncologia Integrada Ltda | Sao Paulo | Brazil | ||
| 54 | Hospital das Clinicas de Faculdade de Medicina da Universidade de Sao | Sao Paulo | Brazil | ||
| 55 | Hospital do Cancer de Sao Paulo-AC Camargo | Sao Paulo | Brazil | ||
| 56 | Hospital do Cancer de Sao Paulo-AC. Camargo | Sao Paulo | Brazil | ||
| 57 | Instituto Brasileiro de Controle do Cancer-IBCC | Sao Paulo | Brazil | ||
| 58 | Burgas | Bulgaria | |||
| 59 | Gabrovo | Bulgaria | |||
| 60 | Pleven | Bulgaria | |||
| 61 | Plovdiv | Bulgaria | |||
| 62 | Ruse | Bulgaria | |||
| 63 | Shumen | Bulgaria | |||
| 64 | Sofia | Bulgaria | |||
| 65 | Stara Zagora | Bulgaria | |||
| 66 | Varna | Bulgaria | |||
| 67 | Kingston | Ontario | Canada | ||
| 68 | Montreal General Hospital | Montreal | Quebec | Canada | H3G 1A4 |
| 69 | Hopital du Sacre-Coeur de Montreal | Montreal | Quebec | Canada | H4J 1C5 |
| 70 | Centre Hospitalier Universitaire de Montreal, Hopital Notre Dame | Montreal | Canada | ||
| 71 | Thunder Bay Regional Health Science Centre Northwestern Ontario | Thunder Bay | Canada | ||
| 72 | Nemocnice Ceske Budejovice, a.s. | Ceske Budejovice | Czechia | ||
| 73 | Onkologicka Klinika, Fakutni Nemocnice | Olomouc | Czechia | ||
| 74 | 1. LF UK, Ustav radiacnej onkologie | Prague 8 | Czechia | ||
| 75 | Krajska nemocnice T. Bati | Zlin Poiters | Czechia | ||
| 76 | Centre Hospitalier La Roche sur Yon, CHD les Oudairies | La Roche sur Yon | France | ||
| 77 | CHU de Poitiers, Service d'Oncologie Medicale | Poitiers Cedex | France | ||
| 78 | Hopital Nord Saint-Etienne | Saint Priest en Jarez | France | ||
| 79 | Augusta-Kranken-Anstalt, Klinik fur Hamatologie und Onkologie | Bochum | Germany | ||
| 80 | Hamburg | Germany | |||
| 81 | Homburg | Germany | |||
| 82 | Universitatsfrauenklinik Magdeburg | Magdeburg | Germany | ||
| 83 | Rostock | Germany | |||
| 84 | Patra | Greece | |||
| 85 | Gyor | Budapest | Hungary | ||
| 86 | Debrecen University | Debrecen | Hungary | ||
| 87 | Debrecen | Hungary | |||
| 88 | Gyula | Hungary | 5700 | ||
| 89 | Pecsi Tudomanyegyetem, Onkoterapias Intezet | Pecs | Hungary | ||
| 90 | Szeged | Hungary | |||
| 91 | Veszprem | Hungary | |||
| 92 | Barzilai Medical Center | Ashkelon | Israel | ||
| 93 | Soroka Medical Center | Beer Sheva | Israel | ||
| 94 | Sharet Institute of Oncology | Jerusalem | Israel | ||
| 95 | Meir Hospital, Sapir Medical Center | Kfar Saba | Israel | ||
| 96 | Rabin Medical Center | Petach Tikva | Israel | ||
| 97 | Kaplan Medical Center | Rechovot | Israel | ||
| 98 | The Chaim Sheba Medical Center | Tel Hashomer | Israel | ||
| 99 | Ancona | Italy | |||
| 100 | Unita Operativa de Oncologia | Lugo | Italy | ||
| 101 | Meldola | Italy | |||
| 102 | Modena | Italy | |||
| 103 | Azienda Ospedaliera San Salvatore | Pesaro | Italy | ||
| 104 | Ospedale Civile S. Maria delle Croci | Ravenna | Italy | ||
| 105 | UO di Onco-ematologia | Rimini | Italy | ||
| 106 | Sassari | Italy | |||
| 107 | Centro Estatal de Cancerologia | Chihuahua | Mexico | ||
| 108 | Monterrey | Mexico | |||
| 109 | Consultorio del Dr. Trigueros | Morelia | Mexico | ||
| 110 | Regionalny Osrodek Onkologii | Bialystok | Poland | ||
| 111 | Bytom | Poland | |||
| 112 | Elblag | Poland | |||
| 113 | Wojewodzkie Centrum Onkologii | Gdansk | Poland | 80-210 | |
| 114 | Krakow | Poland | |||
| 115 | Olsztyn | Poland | 10-513 | ||
| 116 | Rybnik | Poland | 44-200 | ||
| 117 | Torun | Poland | |||
| 118 | Wojewodzki Szpital Specjalistyczny | Wroclaw | Poland | 51-124 | |
| 119 | Cluj-Napoca | Cluj | Romania | 400015 | |
| 120 | Spitalul Militar Central Bucuresti | Bucharest | Romania | 10825 | |
| 121 | Bucuresti | Romania | |||
| 122 | Cluj-Napoca | Romania | |||
| 123 | Centrul de Oncologie Medicala | Iasi | Romania | 700106 | |
| 124 | Spitalul Clinic Judetean Sibiu | Sibiu | Romania | ||
| 125 | Timisoara | Romania | |||
| 126 | Regional Oncology Dispensary | Yaroslavl | Yaroslavlr | Russian Federation | 150054 |
| 127 | Barnaul | Russian Federation | |||
| 128 | Kazan | Russian Federation | |||
| 129 | Kirov | Russian Federation | |||
| 130 | Krasnodar | Russian Federation | |||
| 131 | Blokhin Cancer Research Centre | Moscow | Russian Federation | 115478 | |
| 132 | Moscow | Russian Federation | |||
| 133 | Nizhny Novgorod | Russian Federation | |||
| 134 | Obninsk | Russian Federation | |||
| 135 | Rostov-on-Don | Russian Federation | |||
| 136 | Saint Petersburg | Russian Federation | |||
| 137 | Saratov | Russian Federation | |||
| 138 | Sochi | Russian Federation | |||
| 139 | Tomsk | Russian Federation | |||
| 140 | Vladimir | Russian Federation | |||
| 141 | Singapore | Singapore | |||
| 142 | Mayville | Durban | South Africa | 4091 | |
| 143 | Pretoria | Gaunteng | South Africa | ||
| 144 | Groenkloof | Pretoria | South Africa | ||
| 145 | Panorama Medical Centre | Cape Town | South Africa | ||
| 146 | Durban | South Africa | 4091 | ||
| 147 | Johannesburg | South Africa | |||
| 148 | Sandton | South Africa | 2199 | ||
| 149 | Barakaldo | Vizcaya | Spain | ||
| 150 | Barcelona | Spain | |||
| 151 | Guadalajara | Spain | |||
| 152 | La Coruna | Spain | |||
| 153 | Sevilla | Spain | |||
| 154 | Valencia | Spain | |||
| 155 | Changhua | Taiwan | |||
| 156 | Taichung | Taiwan | |||
| 157 | Tainan City | Taiwan | |||
| 158 | Taipei | Taiwan | |||
| 159 | Yung-Kang City | Taiwan | |||
| 160 | Chernigov | Ukraine | |||
| 161 | Dnepropetrovsk | Ukraine | |||
| 162 | Donetsk | Ukraine | |||
| 163 | Kharkov | Ukraine | |||
| 164 | Khmelnytskyi | Ukraine | |||
| 165 | Kiev | Ukraine | |||
| 166 | Kryvyi Rih | Ukraine | |||
| 167 | Kyiv | Ukraine | |||
| 168 | Lvov | Ukraine | |||
| 169 | Odessa | Ukraine |
Sponsors and Collaborators
- Eisai Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- E7389-G000-301
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | A total of 1276 participants were enrolled and screened, of which 174 were screen failures and 1102 were randomized in the study. Of the randomized participants, 1090 participants received the study treatment. |
| Arm/Group Title | Eribulin Mesylate 1.4 mg/m^2 | Capecitabine 2.5 g/m^2/Day |
|---|---|---|
| Arm/Group Description | Eribulin mesylate 1.4 milligram per meter square (mg/m^2) intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days. | Capecitabine : Capecitabine 2.5 gram per meter square per day (g/m^2/day) administered orally twice daily in two equal doses on Days 1 to 14 every 21 days. |
| Period Title: Overall Study | ||
| STARTED | 554 | 548 |
| Treated (Safety Population) | 544 | 546 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 554 | 548 |
Baseline Characteristics
| Arm/Group Title | Eribulin Mesylate 1.4 mg/m^2 | Capecitabine 2.5 g/m^2/Day | Total |
|---|---|---|---|
| Arm/Group Description | Eribulin mesylate 1.4 mg/m^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days. | Capecitabine : Capecitabine 2.5 g/m^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days. | Total of all reporting groups |
| Overall Participants | 554 | 548 | 1102 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
53.8
(10.37)
|
52.8
(10.20)
|
53.3
(10.29)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
554
100%
|
548
100%
|
1102
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
18
3.2%
|
18
3.3%
|
36
3.3%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
15
2.7%
|
16
2.9%
|
31
2.8%
|
| White |
496
89.5%
|
495
90.3%
|
991
89.9%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
25
4.5%
|
19
3.5%
|
44
4%
|
Outcome Measures
| Title | Overall Survival (OS) |
|---|---|
| Description | 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. |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was analyzed using the Intent-to-Treat (ITT) Population defined as all participants who were randomized. |
| Arm/Group Title | Eribulin Mesylate 1.4 mg/m^2 | Capecitabine 2.5 g/m^2/Day |
|---|---|---|
| Arm/Group Description | Eribulin mesylate 1.4 mg/m^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days. | Capecitabine : Capecitabine 2.5 g/m^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days. |
| Measure Participants | 554 | 548 |
| Median (95% Confidence Interval) [days] |
484
|
440
|
| Title | Progression Free Survival (PFS) |
|---|---|
| Description | 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. |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was analyzed using the ITT Population defined as all participants who were randomized. |
| Arm/Group Title | Eribulin Mesylate 1.4 mg/m^2 | Capecitabine 2.5 g/m^2/Day |
|---|---|---|
| Arm/Group Description | Eribulin mesylate 1.4 mg/m^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days. | Capecitabine : Capecitabine 2.5 g/m^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days. |
| Measure Participants | 554 | 548 |
| Median (95% Confidence Interval) [Days] |
126
|
129
|
| Title | 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 |
|---|---|
| Description | 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. |
| Time Frame | Baseline and Week 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was analyzed using the ITT Population defined as all participants who were randomized. Here,"overall number of participants analyzed" are the participants who were evaluable for this outcome measure. |
| Arm/Group Title | Eribulin Mesylate 1.4 mg/m^2 | Capecitabine 2.5 g/m^2/Day |
|---|---|---|
| Arm/Group Description | Eribulin mesylate 1.4 mg/m^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days. | Capecitabine : Capecitabine 2.5 g/m^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days. |
| Measure Participants | 438 | 406 |
| Mean (Standard Deviation) [units on a scale] |
0.1
(19.23)
|
1.7
(20.69)
|
| Title | 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 |
|---|---|
| Description | 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. |
| Time Frame | Baseline and Week 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was analyzed using the ITT Population defined as all participants who were randomized. Here,"number analyzed" signifies the participants who were evaluable for this outcome measure for individual row. |
| Arm/Group Title | Eribulin Mesylate 1.4 mg/m^2 | Capecitabine 2.5 g/m^2/Day |
|---|---|---|
| Arm/Group Description | Eribulin mesylate 1.4 mg/m^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days. | Capecitabine : Capecitabine 2.5 g/m^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days. |
| Measure Participants | 554 | 548 |
| Body Image |
0.7
(21.26)
|
4.8
(21.80)
|
| Sexual functioning |
1.2
(14.75)
|
-0.1
(16.62)
|
| Sexual enjoyment |
0.8
(21.58)
|
3.1
(17.49)
|
| Future perspective |
7.7
(28.48)
|
10.0
(30.84)
|
| Systemic therapy side effects |
4.5
(15.55)
|
-1.2
(14.73)
|
| Breast Symptoms |
-3.4
(16.55)
|
-3.6
(16.20)
|
| Arm Symptoms |
-4.2
(17.94)
|
-3.4
(18.65)
|
| Upset by hair loss |
-4.4
(32.66)
|
-10.1
(29.76)
|
| Title | Objective Response Rate (ORR): Independent Review |
|---|---|
| Description | 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. |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was analyzed using the ITT Population defined as all participants who were randomized. |
| Arm/Group Title | Eribulin Mesylate 1.4 mg/m^2 | Capecitabine 2.5 g/m^2/Day |
|---|---|---|
| Arm/Group Description | Eribulin mesylate 1.4 mg/m^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days. | Capecitabine : Capecitabine 2.5 g/m^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days. |
| Measure Participants | 554 | 548 |
| Number (95% Confidence Interval) [percentage of participants] |
11.0
2%
|
11.5
2.1%
|
| Title | Duration of Response (DOR): Independent Review |
|---|---|
| Description | 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. |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was analyzed using for a subset of participants in the ITT Population who had a response. Here, "overall number of participants analyzed" are the participants who were evaluable for this outcome measure. |
| Arm/Group Title | Eribulin Mesylate 1.4 mg/m^2 | Capecitabine 2.5 g/m^2/Day |
|---|---|---|
| Arm/Group Description | Eribulin mesylate 1.4 mg/m^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days. | Capecitabine : Capecitabine 2.5 g/m^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days |
| Measure Participants | 61 | 63 |
| Median (95% Confidence Interval) [days] |
198
|
330
|
| Title | Overall Survival Rate |
|---|---|
| Description | 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. |
| Time Frame | From the date of randomization to Year 1, 2 and 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was analyzed using the ITT Population defined as all participants who were randomized. |
| Arm/Group Title | Eribulin Mesylate 1.4 mg/m^2 | Capecitabine 2.5 g/m^2/Day |
|---|---|---|
| Arm/Group Description | Eribulin mesylate 1.4 mg/m^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days. | Capecitabine : Capecitabine 2.5 g/m^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days. |
| Measure Participants | 554 | 548 |
| At 1-year |
0.644
0.1%
|
0.580
0.1%
|
| At 2-years |
0.328
0.1%
|
0.298
0.1%
|
| At 3-years |
0.178
0%
|
0.145
0%
|
| Title | Change From Baseline in Pain Intensity by Visual Analog Scale (VAS) Until 30 Days After the Last Dose of Study Drug |
|---|---|
| Description | 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. |
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was analyzed using the ITT Population defined as all participants who were randomized. Here, "overall number of participants analyzed" are the participants who were evaluable for the outcome measure. |
| Arm/Group Title | Eribulin Mesylate 1.4 mg/m^2 | Capecitabine 2.5 g/m^2/Day |
|---|---|---|
| Arm/Group Description | Eribulin mesylate 1.4 mg/m^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days. | Capecitabine : Capecitabine 2.5 g/m^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days. |
| Measure Participants | 431 | 431 |
| Mean (Standard Deviation) [units on a scale] |
-3.7
(22.80)
|
0.4
(22.90)
|
| Title | Number of Participants With Consumption of Analgesics During the Study |
|---|---|
| Description | 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 |
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was analyzed using safety population defined as all participants who received at least one dose of study treatment. |
| Arm/Group Title | Eribulin Mesylate 1.4 mg/m^2 | Capecitabine 2.5 g/m^2/Day |
|---|---|---|
| Arm/Group Description | Eribulin mesylate 1.4 mg/m^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days. | Capecitabine : Capecitabine 2.5 g/m^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days. |
| Measure Participants | 544 | 546 |
| Count of Participants [Participants] |
222
40.1%
|
196
35.8%
|
| Title | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
|---|---|
| Description | TEAEs included both SAEs as well as non-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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was analyzed using safety population defined as all participants who received at least one dose of study treatment. |
| Arm/Group Title | Eribulin Mesylate 1.4 mg/m^2 | Capecitabine 2.5 g/m^2/Day |
|---|---|---|
| Arm/Group Description | Eribulin mesylate 1.4 mg/m^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days. | Capecitabine : Capecitabine 2.5 g/m^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days |
| Measure Participants | 544 | 546 |
| TEAEs |
512
92.4%
|
494
90.1%
|
| SAEs |
95
17.1%
|
115
21%
|
| Title | Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Parameter Values |
|---|---|
| Description | |
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was analyzed using safety population defined as all participants who received at least one dose of study treatment. |
| Arm/Group Title | Eribulin Mesylate 1.4 mg/m^2 | Capecitabine 2.5 g/m^2/Day |
|---|---|---|
| Arm/Group Description | Eribulin mesylate 1.4 mg/m^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days. | Capecitabine : Capecitabine 2.5 g/m^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days. |
| Measure Participants | 544 | 546 |
| Count of Participants [Participants] |
362
65.3%
|
224
40.9%
|
| Title | Number of Participants Who Took at Least One Concomitant Medication |
|---|---|
| Description | 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. |
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was analyzed using safety population defined as all participants who received at least one dose of study treatment. |
| Arm/Group Title | Eribulin Mesylate 1.4 mg/m^2 | Capecitabine 2.5 g/m^2/Day |
|---|---|---|
| Arm/Group Description | Eribulin mesylate 1.4 mg/m^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days. | Capecitabine : Capecitabine 2.5 g/m^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days. |
| Measure Participants | 544 | 546 |
| Count of Participants [Participants] |
496
89.5%
|
483
88.1%
|
| Title | Duration of Eribulin Mesylate Exposure |
|---|---|
| Description | 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. |
| Time Frame | Up to approximately 6 years for primary analysis completion stage, Up to approximately 6 years 2 months for final analysis completion stage |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was analyzed using safety population defined as all participants who received at least one dose of study treatment. Here, "number analyzed" signifies the participants who were evaluable at individual stage for this outcome measure. |
| Arm/Group Title | Eribulin Mesylate 1.4 mg/m^2 | Capecitabine 2.5 g/m^2/Day |
|---|---|---|
| Arm/Group Description | Eribulin mesylate 1.4 mg/m^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days. | Capecitabine : Capecitabine 2.5 g/m^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days. |
| Measure Participants | 544 | 546 |
| At primary analysis completion stage |
125.0
|
119.0
|
| At final analysis completion stage |
1743.0
|
1506.0
|
| Title | Plasma Concentrations of Eribulin Mesylate |
|---|---|
| Description | |
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic (PK) analysis set included all participants who have received at least one dose of E7389 and have at least one quantifiable E7389 concentration. Here, "number analyzed" signifies the participants who were evaluable for this outcome measure for given time points. |
| Arm/Group Title | Eribulin Mesylate 1.4 mg/m^2 |
|---|---|
| Arm/Group Description | Eribulin mesylate 1.4 mg/m^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days. |
| Measure Participants | 173 |
| 5-10 minutes |
415.8
(719.5)
|
| 15-30 minutes |
152.6
(70.51)
|
| 30-60 minutes |
95.5
(87.90)
|
| 60-90 minutes |
52.7
(79.33)
|
| 2-4 hours |
20.7
(32.81)
|
| 4-8 hours |
10.0
(5.40)
|
| 10-24 hours |
5.8
(3.72)
|
| 48-72 hours |
3.7
(2.58)
|
| 72-96 hours |
2.4
(1.60)
|
| 96-120 hours |
7.6
(38.75)
|
Adverse Events
| 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) | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Data was analyzed using Safety Population defined as all participants who received at least one dose of study treatment. | |||
| Arm/Group Title | Eribulin Mesylate 1.4 mg/m^2 | Capecitabine 2.5 g/m^2/Day | ||
| Arm/Group Description | Eribulin mesylate 1.4 mg/m^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days | Capecitabine : Capecitabine 2.5 g/m^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days | ||
All Cause Mortality |
||||
| Eribulin Mesylate 1.4 mg/m^2 | Capecitabine 2.5 g/m^2/Day | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 442/544 (81.3%) | 459/546 (84.1%) | ||
Serious Adverse Events |
||||
| Eribulin Mesylate 1.4 mg/m^2 | Capecitabine 2.5 g/m^2/Day | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 95/544 (17.5%) | 115/546 (21.1%) | ||
| Blood and lymphatic system disorders | ||||
| Neutropenia | 10/544 (1.8%) | 1/546 (0.2%) | ||
| Febrile Neutropenia | 7/544 (1.3%) | 4/546 (0.7%) | ||
| Leukopenia | 4/544 (0.7%) | 0/546 (0%) | ||
| Anaemia | 3/544 (0.6%) | 0/546 (0%) | ||
| Pancytopenia | 1/544 (0.2%) | 1/546 (0.2%) | ||
| Thrombocytopenia | 0/544 (0%) | 1/546 (0.2%) | ||
| Cardiac disorders | ||||
| Cardiopulmonary Failure | 1/544 (0.2%) | 1/546 (0.2%) | ||
| Myocardial Infarction | 1/544 (0.2%) | 1/546 (0.2%) | ||
| Pericardial Effusion | 1/544 (0.2%) | 1/546 (0.2%) | ||
| Angina Pectoris | 1/544 (0.2%) | 0/546 (0%) | ||
| Left Ventricular Dysfunction | 1/544 (0.2%) | 0/546 (0%) | ||
| Tachycardia | 1/544 (0.2%) | 0/546 (0%) | ||
| Cardiac Failure | 0/544 (0%) | 2/546 (0.4%) | ||
| Acute Myocardial Infarction | 0/544 (0%) | 1/546 (0.2%) | ||
| Bradycardia | 0/544 (0%) | 1/546 (0.2%) | ||
| Cardiac Tamponade | 0/544 (0%) | 1/546 (0.2%) | ||
| Cardio-respiratory Arrest | 0/544 (0%) | 1/546 (0.2%) | ||
| Cardiogenic Shock | 0/544 (0%) | 1/546 (0.2%) | ||
| Ear and labyrinth disorders | ||||
| Vertigo | 1/544 (0.2%) | 0/546 (0%) | ||
| Gastrointestinal disorders | ||||
| Vomiting | 2/544 (0.4%) | 9/546 (1.6%) | ||
| Abdominal Pain | 2/544 (0.4%) | 1/546 (0.2%) | ||
| Diarrhoea | 1/544 (0.2%) | 15/546 (2.7%) | ||
| Nausea | 1/544 (0.2%) | 7/546 (1.3%) | ||
| Gastrointestinal Haemorrhage | 1/544 (0.2%) | 0/546 (0%) | ||
| Haematemesis | 1/544 (0.2%) | 0/546 (0%) | ||
| Haematochezia | 1/544 (0.2%) | 0/546 (0%) | ||
| Haemorrhoids | 1/544 (0.2%) | 0/546 (0%) | ||
| Intestinal Ischaemia | 1/544 (0.2%) | 0/546 (0%) | ||
| Dysphagia | 0/544 (0%) | 2/546 (0.4%) | ||
| Constipation | 0/544 (0%) | 1/546 (0.2%) | ||
| Intestinal Obstruction | 1/544 (0.2%) | 0/546 (0%) | ||
| Stomatitis | 1/544 (0.2%) | 1/546 (0.2%) | ||
| General disorders | ||||
| Pyrexia | 3/544 (0.6%) | 5/546 (0.9%) | ||
| Asthenia | 3/544 (0.6%) | 4/546 (0.7%) | ||
| Fatigue | 3/544 (0.6%) | 4/546 (0.7%) | ||
| Death | 2/544 (0.4%) | 2/546 (0.4%) | ||
| General Physical Health Deterioration | 2/544 (0.4%) | 3/546 (0.5%) | ||
| Multi-Organ Failure | 1/544 (0.2%) | 2/546 (0.4%) | ||
| Extravasation | 1/544 (0.2%) | 0/546 (0%) | ||
| Influenza Like Illness | 1/544 (0.2%) | 0/546 (0%) | ||
| Sudden Death | 1/544 (0.2%) | 0/546 (0%) | ||
| Mucosal Inflammation | 0/544 (0%) | 2/546 (0.4%) | ||
| Generalized Edema | 0/544 (0%) | 1/546 (0.2%) | ||
| Injection Site Extravasation | 0/544 (0%) | 1/546 (0.2%) | ||
| Oedema Peripheral | 0/544 (0%) | 1/546 (0.2%) | ||
| Hepatobiliary disorders | ||||
| Hepatitis Toxic | 1/544 (0.2%) | 0/546 (0%) | ||
| Hepatic Failure | 1/544 (0.2%) | 1/546 (0.2%) | ||
| Cholelithiasis | 1/544 (0.2%) | 0/546 (0%) | ||
| Immune system disorders | ||||
| Hypersensitivity | 1/544 (0.2%) | 1/546 (0.2%) | ||
| Infections and infestations | ||||
| Pneumonia | 4/544 (0.7%) | 4/546 (0.7%) | ||
| Sepsis | 2/544 (0.4%) | 4/546 (0.7%) | ||
| Bronchopneumonia | 1/544 (0.2%) | 1/546 (0.2%) | ||
| Hepatitis C | 1/544 (0.2%) | 0/546 (0%) | ||
| Lung Infection | 1/544 (0.2%) | 0/546 (0%) | ||
| Pneumonia Klebsiella | 1/544 (0.2%) | 0/546 (0%) | ||
| Respiratory Tract Infection | 1/544 (0.2%) | 0/546 (0%) | ||
| Soft Tissue Infection | 1/544 (0.2%) | 0/546 (0%) | ||
| Upper Respiratory Tract Infection | 1/544 (0.2%) | 0/546 (0%) | ||
| Urinary Tract Infection | 1/544 (0.2%) | 0/546 (0%) | ||
| Bronchitis | 0/544 (0%) | 3/546 (0.5%) | ||
| Cellulitis | 0/544 (0%) | 2/546 (0.4%) | ||
| Staphylococcal Infection | 0/544 (0%) | 1/546 (0.2%) | ||
| Subcutaneous Abscess | 0/544 (0%) | 1/546 (0.2%) | ||
| Injury, poisoning and procedural complications | ||||
| Femur Fracture | 1/544 (0.2%) | 2/546 (0.4%) | ||
| Accidental Overdose | 1/544 (0.2%) | 1/546 (0.2%) | ||
| Femoral Neck Fracture | 1/544 (0.2%) | 1/546 (0.2%) | ||
| Hip Fracture | 1/544 (0.2%) | 0/546 (0%) | ||
| Humerus Fracture | 1/544 (0.2%) | 0/546 (0%) | ||
| Lumbar Vertebral Fracture | 1/544 (0.2%) | 0/546 (0%) | ||
| Joint Dislocation | 0/544 (0%) | 1/546 (0.2%) | ||
| Investigations | ||||
| Haemoglobin Decreased | 1/544 (0.2%) | 0/546 (0%) | ||
| Aspartate Aminotransferase Increased | 0/544 (0%) | 1/546 (0.2%) | ||
| Hepatic Enzyme Increased | 0/544 (0%) | 1/546 (0.2%) | ||
| Troponin Increased | 0/544 (0%) | 1/546 (0.2%) | ||
| Metabolism and nutrition disorders | ||||
| Dehydration | 1/544 (0.2%) | 9/546 (1.6%) | ||
| Hyperglycaemia | 1/544 (0.2%) | 2/546 (0.4%) | ||
| Decreased Appetite | 1/544 (0.2%) | 1/546 (0.2%) | ||
| Hypercalcaemia | 1/544 (0.2%) | 1/546 (0.2%) | ||
| Electrolyte Imbalance | 0/544 (0%) | 1/546 (0.2%) | ||
| Hypokalaemia | 0/544 (0%) | 1/546 (0.2%) | ||
| Hyponatraemia | 0/544 (0%) | 1/546 (0.2%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back Pain | 2/544 (0.4%) | 0/546 (0%) | ||
| Muscular Weakness | 1/544 (0.2%) | 0/546 (0%) | ||
| Pathological Fracture | 1/544 (0.2%) | 0/546 (0%) | ||
| Arthralgia | 0/544 (0%) | 1/546 (0.2%) | ||
| Bone Pain | 0/544 (0%) | 1/546 (0.2%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Neoplasm Malignant | 7/544 (1.3%) | 4/546 (0.7%) | ||
| Metastases to Liver | 1/544 (0.2%) | 1/546 (0.2%) | ||
| Metastases to Meninges | 1/544 (0.2%) | 0/546 (0%) | ||
| Metastases to Ovary | 1/544 (0.2%) | 0/546 (0%) | ||
| Metastases to Peritoneum | 1/544 (0.2%) | 0/546 (0%) | ||
| Oncologic Complication | 0/544 (0%) | 2/546 (0.4%) | ||
| Tumour Pain | 0/544 (0%) | 2/546 (0.4%) | ||
| Malignant Ascites | 0/544 (0%) | 1/546 (0.2%) | ||
| Malignant Pleural Effusion | 0/544 (0%) | 1/546 (0.2%) | ||
| Metastases to Central Nervous System | 0/544 (0%) | 1/546 (0.2%) | ||
| Metastases to Pleura | 0/544 (0%) | 1/546 (0.2%) | ||
| Rectal Cancer | 0/544 (0%) | 1/546 (0.2%) | ||
| Nervous system disorders | ||||
| Headache | 2/544 (0.4%) | 4/546 (0.7%) | ||
| Cerebrovascular Accident | 2/544 (0.4%) | 2/546 (0.4%) | ||
| Spinal Cord Compression | 2/544 (0.4%) | 2/546 (0.4%) | ||
| Convulsion | 1/544 (0.2%) | 2/546 (0.4%) | ||
| Dizziness | 1/544 (0.2%) | 0/546 (0%) | ||
| Facial Paresis | 1/544 (0.2%) | 0/546 (0%) | ||
| Myoclonic Epilepsy | 1/544 (0.2%) | 0/546 (0%) | ||
| Partial Seizures | 1/544 (0.2%) | 0/546 (0%) | ||
| Peripheral Motor Neuropathy | 1/544 (0.2%) | 0/546 (0%) | ||
| Peripheral Sensory Neuropathy | 1/544 (0.2%) | 0/546 (0%) | ||
| Syncope | 1/544 (0.2%) | 0/546 (0%) | ||
| Transient Ischaemic Attack | 1/544 (0.2%) | 0/546 (0%) | ||
| Depressed Level of Consciousness | 0/544 (0%) | 2/546 (0.4%) | ||
| Aphasia | 0/544 (0%) | 1/546 (0.2%) | ||
| Cerebellar Infarction | 0/544 (0%) | 1/546 (0.2%) | ||
| Coma Hepatic | 0/544 (0%) | 1/546 (0.2%) | ||
| Dysgeuesia | 0/544 (0%) | 1/546 (0.2%) | ||
| Intracranial Pressure Increased | 0/544 (0%) | 1/546 (0.2%) | ||
| Lethargy | 0/544 (0%) | 1/546 (0.2%) | ||
| Simple Partial Seizures | 0/544 (0%) | 1/546 (0.2%) | ||
| Somnolence | 0/544 (0%) | 1/546 (0.2%) | ||
| Psychiatric disorders | ||||
| Confusional State | 2/544 (0.4%) | 0/546 (0%) | ||
| Mental status changes | 2/544 (0.4%) | 1/546 (0.2%) | ||
| Renal and urinary disorders | ||||
| Renal Failure | 1/544 (0.2%) | 1/546 (0.2%) | ||
| Renal Failure Acute | 1/544 (0.2%) | 1/546 (0.2%) | ||
| Haematuria | 0/544 (0%) | 1/546 (0.2%) | ||
| Hydronephrosis | 0/544 (0%) | 1/546 (0.2%) | ||
| Reproductive system and breast disorders | ||||
| Vaginal Haemorrhage | 0/544 (0%) | 1/546 (0.2%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnoea | 13/544 (2.4%) | 17/546 (3.1%) | ||
| Respiratory Failure | 5/544 (0.9%) | 7/546 (1.3%) | ||
| Pleural Effusion | 2/544 (0.4%) | 2/546 (0.4%) | ||
| Pulmonary Embolism | 1/544 (0.2%) | 3/546 (0.5%) | ||
| Hydrothorax | 1/544 (0.2%) | 2/546 (0.4%) | ||
| Acute Respiratory Failure | 1/544 (0.2%) | 1/546 (0.2%) | ||
| Epistaxis | 1/544 (0.2%) | 0/546 (0%) | ||
| Tracheal Stenosis | 1/544 (0.2%) | 0/546 (0%) | ||
| Respiratory Distress | 0/544 (0%) | 2/546 (0.4%) | ||
| Cough | 0/544 (0%) | 1/546 (0.2%) | ||
| Dyspnoea Exertional | 0/544 (0%) | 1/546 (0.2%) | ||
| Pneumothorax | 0/544 (0%) | 1/546 (0.2%) | ||
| Wheezing | 0/544 (0%) | 1/546 (0.2%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Palmar-Plantar Erythrodysaesthesia | 0/544 (0%) | 2/546 (0.4%) | ||
| Surgical and medical procedures | ||||
| Malignant Breast Lump Removal | 0/544 (0%) | 1/546 (0.2%) | ||
| Vascular disorders | ||||
| Deep Vein Thrombosis | 2/544 (0.4%) | 3/546 (0.5%) | ||
| Hypotension | 1/544 (0.2%) | 1/546 (0.2%) | ||
| Thrombophlebitis | 1/544 (0.2%) | 0/546 (0%) | ||
| Hypertension | 0/544 (0%) | 1/546 (0.2%) | ||
| Shock Haemorrhagic | 0/544 (0%) | 1/546 (0.2%) | ||
| Thrombosis | 0/544 (0%) | 1/546 (0.2%) | ||
| Haemorrhage | 0/544 (0%) | 1/546 (0.2%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Eribulin Mesylate 1.4 mg/m^2 | Capecitabine 2.5 g/m^2/Day | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 509/544 (93.6%) | 489/546 (89.6%) | ||
| Blood and lymphatic system disorders | ||||
| Neutropenia | 292/544 (53.7%) | 87/546 (15.9%) | ||
| Leukopenia | 171/544 (31.4%) | 57/546 (10.4%) | ||
| Anaemia | 102/544 (18.8%) | 96/546 (17.6%) | ||
| Thrombocytopenia | 27/544 (5%) | 29/546 (5.3%) | ||
| Gastrointestinal disorders | ||||
| Nausea | 121/544 (22.2%) | 131/546 (24%) | ||
| Diarrhoea | 77/544 (14.2%) | 154/546 (28.2%) | ||
| Vomiting | 63/544 (11.6%) | 89/546 (16.3%) | ||
| Constipation | 42/544 (7.7%) | 46/546 (8.4%) | ||
| Abdominal Pain | 32/544 (5.9%) | 46/546 (8.4%) | ||
| Abdominal Pain Upper | 31/544 (5.7%) | 39/546 (7.1%) | ||
| Stomatitis | 27/544 (5%) | 31/546 (5.7%) | ||
| General disorders | ||||
| Fatigue | 91/544 (16.7%) | 82/546 (15%) | ||
| Asthenia | 83/544 (15.3%) | 79/546 (14.5%) | ||
| Pyrexia | 67/544 (12.3%) | 27/546 (4.9%) | ||
| Oedema Peripheral | 35/544 (6.4%) | 36/546 (6.6%) | ||
| Mucosal Inflammation | 26/544 (4.8%) | 35/546 (6.4%) | ||
| Hepatobiliary disorders | ||||
| Hyperbilirubinaemia | 9/544 (1.7%) | 38/546 (7%) | ||
| Infections and infestations | ||||
| Urinary Tract Infection | 29/544 (5.3%) | 26/546 (4.8%) | ||
| Investigations | ||||
| Alanine Aminotransferase Increased | 47/544 (8.6%) | 23/546 (4.2%) | ||
| Aspartate Aminotransferase Increased | 43/544 (7.9%) | 27/546 (4.9%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased Appetite | 68/544 (12.5%) | 80/546 (14.7%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back Pain | 55/544 (10.1%) | 43/546 (7.9%) | ||
| Bone Pain | 50/544 (9.2%) | 42/546 (7.7%) | ||
| Pain in Extremity | 47/544 (8.6%) | 37/546 (6.8%) | ||
| Arthralgia | 42/544 (7.7%) | 31/546 (5.7%) | ||
| Myalgia | 30/544 (5.5%) | 8/546 (1.5%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Tumour Pain | 29/544 (5.3%) | 22/546 (4%) | ||
| Nervous system disorders | ||||
| Peripheral Sensory Neuropathy | 73/544 (13.4%) | 38/546 (7%) | ||
| Headache | 67/544 (12.3%) | 55/546 (10.1%) | ||
| Dizziness | 30/544 (5.5%) | 29/546 (5.3%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnoea | 49/544 (9%) | 51/546 (9.3%) | ||
| Cough | 45/544 (8.3%) | 44/546 (8.1%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 188/544 (34.6%) | 22/546 (4%) | ||
| Palmar-Plantar Erythrodysaesthesia Syndrome | 1/544 (0.2%) | 244/546 (44.7%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Eisai Medical Information |
|---|---|
| Organization | Eisai Inc. |
| Phone | 1-888-274-2378 |
| esi_oncmedinfo@eisai.com |
- E7389-G000-301