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CompletedNCT00337103Updated Jun 18, 2020Results posted

E7389 Versus Capecitabine in Patients With Locally Advanced or Metastatic Breast Cancer Previously Treated With Anthracyclines and Taxanes

A Phase 3 interventional study of Eribulin Mesylate and Capecitabine in Metastatic Breast Cancer, sponsored by Eisai Inc.. Completed at 169 sites in 23 countries. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-06-18.

Sponsored by Eisai Inc. · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
1,276
Allocation
Randomized
Ages
18 Years and older
Sex
Female
01

Study 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.

02

Conditions studied

  • Metastatic Breast Cancer

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03

In context

Breast Neoplasms

12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.

This study's enrollment of 1,276 is above the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.

Browse Breast Neoplasms studies →

Lead sponsor

Eisai Inc. is the lead sponsor of 360 studies on the registry; 7 are open to participants now.

Of its 81 completed or terminated interventional studies of FDA-regulated products, 54 (67%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Female
Accepts healthy volunteers
No

Inclusion criteria

  1. 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.

  2. 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.
  3. Resolution of all chemotherapy or radiation-related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy \<= Grade 2 and alopecia.
  4. Age >= 18 years.
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
  6. Life expectancy of >= 3 months.
  7. 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.
  8. 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.
  9. 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.
  10. 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).
  11. Patients willing and able to comply with the study protocol for the duration of the study.
  12. 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

Exclusion Criteria:

  1. 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).
  2. Patients who have received capecitabine as a prior therapy for their disease.
  3. 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.
  4. Radiation therapy encompassing > 30% of marrow.
  5. Prior treatment with mitomycin C or nitrosourea.
  6. Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen.
  7. 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.
  8. Patients with meningeal carcinomatosis.
  9. 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.
  10. 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.
  11. Severe/uncontrolled intercurrent illness/infection.
  12. 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).
  13. Patients with organ allografts requiring immunosuppression.
  14. Patients with known positive human immunodeficiency virus (HIV) status.
  15. 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.
  16. Patients with pre-existing neuropathy > Grade 2.
  17. Patients with a hypersensitivity to halichondrin B and/or halichondrin B chemical derivative.
  18. Patients who participated in a prior E7389 clinical trial.
  19. Patients with other significant disease or disorders that, in the Investigator's opinion, would exclude the patient from the study.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
1,276 participants (actual)

Study arms

  • Experimental
    1

    Drug: Eribulin Mesylate

  • Active comparator
    2

    Drug: Capecitabine

Interventions

  • DrugEribulin Mesylate

    1.4 mg/m\^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days

  • DrugCapecitabine

    Capecitabine 2.5 g/m\^2/day administered orally twice daily in two equal doses on Days 1 to 14 every 21 days

06

What researchers measure

Primary outcomes

  1. 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.

    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

  2. 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.

    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

Secondary outcomes

  1. 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.

    Time frame: Baseline and Week 6

  2. 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.

    Time frame: Baseline and Week 6

  3. 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.

    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

  4. 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.

    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

  5. 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.

    Time frame: From the date of randomization to Year 1, 2 and 3

  6. 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.

    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)

  7. 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

    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)

  8. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    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)

  9. 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)

  10. 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.

    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)

  11. 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.

    Time frame: Up to approximately 6 years for primary analysis completion stage, Up to approximately 6 years 2 months for final analysis completion stage

  12. 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)

07

Results

Posted Sep 30, 2013

Participant flow

Participant flow — Overall Study
MilestoneEribulin Mesylate 1.4 mg/m^2Capecitabine 2.5 g/m^2/Day
Started554548
Treated (safety population)544546
Completed00
Not completed554548
Withdrew: Progressive disease414410
Withdrew: Adverse event4559
Withdrew: Subject choice3427
Withdrew: Clinical progression2724
Withdrew: Physician decision1514
Withdrew: Withdrawal by subject85
Withdrew: Other56
Withdrew: Entry criteria not met41
Withdrew: Lost to follow-up12
Withdrew: Death10

Outcome measures

PrimaryOverall 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.

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
Reported as:
Median · days
Overall Survival (OS)
daysEribulin Mesylate 1.4 mg/m^2Capecitabine 2.5 g/m^2/Day
Overall Survival (OS)484 (462 to 536)440 (400 to 487)
PrimaryProgression 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.

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
Reported as:
Median · Days
Progression Free Survival (PFS)
DaysEribulin Mesylate 1.4 mg/m^2Capecitabine 2.5 g/m^2/Day
Progression Free Survival (PFS)126 (106 to 131)129 (120 to 147)
SecondaryChange 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.

Time frame:
Baseline and Week 6
Reported as:
Mean · units on a scale
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
units on a scaleEribulin Mesylate 1.4 mg/m^2Capecitabine 2.5 g/m^2/Day
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 60.1 ± 19.231.7 ± 20.69
SecondaryChange 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.

Time frame:
Baseline and Week 6
Reported as:
Mean · units on a scale
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
units on a scaleEribulin Mesylate 1.4 mg/m^2Capecitabine 2.5 g/m^2/Day
Body Image0.7 ± 21.264.8 ± 21.80
Sexual functioning1.2 ± 14.75-0.1 ± 16.62
Sexual enjoyment0.8 ± 21.583.1 ± 17.49
Future perspective7.7 ± 28.4810.0 ± 30.84
Systemic therapy side effects4.5 ± 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
SecondaryObjective 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.

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
Reported as:
Number · percentage of participants
Objective Response Rate (ORR): Independent Review
percentage of participantsEribulin Mesylate 1.4 mg/m^2Capecitabine 2.5 g/m^2/Day
Objective Response Rate (ORR): Independent Review11.0 (8.5 to 13.9)11.5 (8.9 to 14.5)
SecondaryDuration 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.

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
Reported as:
Median · days
Duration of Response (DOR): Independent Review
daysEribulin Mesylate 1.4 mg/m^2Capecitabine 2.5 g/m^2/Day
Duration of Response (DOR): Independent Review198 (150 to 273)330 (208 to 541)
SecondaryOverall 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.

Time frame:
From the date of randomization to Year 1, 2 and 3
Reported as:
Number · percentage of participants
Overall Survival Rate
percentage of participantsEribulin Mesylate 1.4 mg/m^2Capecitabine 2.5 g/m^2/Day
At 1-year0.644 (0.604 to 0.684)0.580 (0.538 to 0.622)
At 2-years0.328 (0.289 to 0.368)0.298 (0.259 to 0.337)
At 3-years0.178 (0.144 to 0.212)0.145 (0.113 to 0.177)
SecondaryChange 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.

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)
Reported as:
Mean · units on a scale
Change From Baseline in Pain Intensity by Visual Analog Scale (VAS) Until 30 Days After the Last Dose of Study Drug
units on a scaleEribulin Mesylate 1.4 mg/m^2Capecitabine 2.5 g/m^2/Day
Change From Baseline in Pain Intensity by Visual Analog Scale (VAS) Until 30 Days After the Last Dose of Study Drug-3.7 ± 22.800.4 ± 22.90
SecondaryNumber 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

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)
Reported as:
Count of participants · Participants
Number of Participants With Consumption of Analgesics During the Study
ParticipantsEribulin Mesylate 1.4 mg/m^2Capecitabine 2.5 g/m^2/Day
Number of Participants With Consumption of Analgesics During the Study222196
SecondaryNumber of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

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)
Reported as:
Count of participants · Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
ParticipantsEribulin Mesylate 1.4 mg/m^2Capecitabine 2.5 g/m^2/Day
TEAEs512494
SAEs95115
SecondaryNumber 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)
Reported as:
Count of participants · Participants
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Parameter Values
ParticipantsEribulin Mesylate 1.4 mg/m^2Capecitabine 2.5 g/m^2/Day
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Parameter Values362224
SecondaryNumber 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.

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)
Reported as:
Count of participants · Participants
Number of Participants Who Took at Least One Concomitant Medication
ParticipantsEribulin Mesylate 1.4 mg/m^2Capecitabine 2.5 g/m^2/Day
Number of Participants Who Took at Least One Concomitant Medication496483
SecondaryDuration 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.

Time frame:
Up to approximately 6 years for primary analysis completion stage, Up to approximately 6 years 2 months for final analysis completion stage
Reported as:
Median · days
Duration of Eribulin Mesylate Exposure
daysEribulin Mesylate 1.4 mg/m^2Capecitabine 2.5 g/m^2/Day
At primary analysis completion stage125.0 (21 to 1372)119.0 (21 to 1442)
At final analysis completion stage1743.0 (1561 to 2219)1506.0 (1175 to 2296)
SecondaryPlasma 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)
Reported as:
Mean · nanogram per milliliter (ng/mL)
Plasma Concentrations of Eribulin Mesylate
nanogram per milliliter (ng/mL)Eribulin Mesylate 1.4 mg/m^2
5-10 minutes415.8 ± 719.5
15-30 minutes152.6 ± 70.51
30-60 minutes95.5 ± 87.90
60-90 minutes52.7 ± 79.33
2-4 hours20.7 ± 32.81
4-8 hours10.0 ± 5.40
10-24 hours5.8 ± 3.72
48-72 hours3.7 ± 2.58
72-96 hours2.4 ± 1.60
96-120 hours7.6 ± 38.75

Adverse events

Collected over First dose of study drug (Baseline) up to 30 days after last dose of study drug (up to approximately 6 years 3 months). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Eribulin Mesylate 1.4 mg/m^2442/544 (81.3%)95/544 (17.5%)509/544 (93.6%)
Capecitabine 2.5 g/m^2/Day459/546 (84.1%)115/546 (21.1%)489/546 (89.6%)
Most frequent serious events
Showing 10 of 148
Most frequent serious events
EventEribulin Mesylate 1.4 mg/m^2Capecitabine 2.5 g/m^2/Day
DyspnoeaRespiratory, thoracic and mediastinal disorders13/54417/546
DiarrhoeaGastrointestinal disorders1/54415/546
NeutropeniaBlood and lymphatic system disorders10/5441/546
VomitingGastrointestinal disorders2/5449/546
DehydrationMetabolism and nutrition disorders1/5449/546
Febrile NeutropeniaBlood and lymphatic system disorders7/5444/546
Neoplasm MalignantNeoplasms benign, malignant and unspecified (incl cysts and polyps)7/5444/546
Respiratory FailureRespiratory, thoracic and mediastinal disorders5/5447/546
NauseaGastrointestinal disorders1/5447/546
PyrexiaGeneral disorders3/5445/546
Most frequent other events
Showing 10 of 34
Most frequent other events
EventEribulin Mesylate 1.4 mg/m^2Capecitabine 2.5 g/m^2/Day
NeutropeniaBlood and lymphatic system disorders292/54487/546
Palmar-Plantar Erythrodysaesthesia SyndromeSkin and subcutaneous tissue disorders1/544244/546
AlopeciaSkin and subcutaneous tissue disorders188/54422/546
LeukopeniaBlood and lymphatic system disorders171/54457/546
DiarrhoeaGastrointestinal disorders77/544154/546
NauseaGastrointestinal disorders121/544131/546
AnaemiaBlood and lymphatic system disorders102/54496/546
FatigueGeneral disorders91/54482/546
VomitingGastrointestinal disorders63/54489/546
AstheniaGeneral disorders83/54479/546

Baseline characteristics

Age, Continuous
Age, Continuous(years)Eribulin Mesylate 1.4 mg/m^2Capecitabine 2.5 g/m^2/DayTotal
Mean53.8 ± 10.3752.8 ± 10.2053.3 ± 10.29
Sex: Female, Male
Sex: Female, Male(Participants)Eribulin Mesylate 1.4 mg/m^2Capecitabine 2.5 g/m^2/DayTotal
Female5545481102
Male000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Eribulin Mesylate 1.4 mg/m^2Capecitabine 2.5 g/m^2/DayTotal
American Indian or Alaska Native000
Asian181836
Native Hawaiian or Other Pacific Islander000
Black or African American151631
White496495991
More than one race000
Unknown or Not Reported251944
08

Study locations

169 sites
  • Anaheim, California, United States
  • La Verne, California, United States
  • Poway, California, United States
  • Centralia, Illinois, United States
  • Augusta, Maine, United States
  • Boston, Massachusetts, United States
  • Jefferson City, Missouri, United States
  • Lebanon, New Hampshire, United States
  • Ephrata, Pennsylvania, United States
  • Cookeville, Tennessee, United States
  • Germantown, Tennessee, United States
  • Amarillo, Texas, United States
  • Wenatchee, Washington, United States
  • Hospital General de Agudos Teodoro Alvarez
    Ciudad Autonoma, Buenos Aires C1406FWY, Argentina
  • Instituto Argentino de Diagnostico y Tratamiento
    Cuidad Autonoma de Buenos Aires, Buenos Aires, Argentina
  • La Plata, Buenos Aires 1898, Argentina
  • La Plata, Buenos Aires, Argentina
  • Pilar, Buenos Aires B1629AHJ, Argentina
  • Corporacion Medica General San Martin
    San Martin, Buenos Aires, Argentina
  • Rosario, Santa Fe S2000DSK, Argentina
  • San Miguel de Tucuman, Tucuman T4000IAK, Argentina
  • Bahia Blanca, Bema 8000, Argentina
  • Buenos Aires, C1280AEB, Argentina
  • Buenos Aires, Argentina
  • Hospital Italiano de Buenos Aires
    Ciudad Autonoma de Buenos Aires, Argentina
  • Ciudad Autonoma, Argentina
  • Mendoza, Argentina
  • Santa Fe, S3000FFU, Argentina
  • Bankstown Hospital, Oncology Trials Unit
    Bankstown, New South Wales, Australia
  • Hornsby, New South Wales 2077, Australia
  • Liverpool Hospital, Cancer Therapy Centre
    Liverpool, New South Wales, Australia
  • Ashford Cancer Centre
    Adelaide, South Australia 5035, Australia
  • Royal Hobart Hospital
    Hobart, Tasmania 7000, Australia
  • Saint Vincent's Hospital
    Fitzroy, Victoria 3065, Australia
  • Royal Perth Hospital
    Perth, Western Australia 6000, Australia
  • Epworth Freemasons Hospital
    East Melbourne, Australia
  • Sir Charles Gairdner Hospital, Dept. of Medical Oncology
    Nedlands, Australia
  • Mater Adult Hospital
    South Brisbane, Australia
  • OLVZ Aalst, Oncology Service
    Aalst, 9300, Belgium
  • Institut Jules Bordet, Medical Oncology Unit
    Brussels, 1000, Belgium
  • Algemeen Ziekenhuis Sint Lucas
    Ghent, 9000, Belgium
  • Centre Hosptialier Universitaire Sart Tilman Liege
    Liege, Belgium
  • Florianopolis, Brazil
  • Associacao Hospital de Caridade Ijui
    Ijui, Brazil
  • Instituto de Oncologia Ltda
    Jundiai, Brazil
  • Proonco Centro de Tratamento Oncologico
    Londrina, Brazil
  • Hospital de Clinicas de Porto Alegre, Servicio de Oncologia
    Porto Alegre, Brazil
  • Hospital Nossa Senhora da Conceicao
    Porto Alegre, Brazil
  • Servico de Quimioterapia de Pernambuco-SEQUIPE
    Recife, Brazil
  • Instituto Ribeiraopretano de Combate ao Cancer
    Ribeirao Preto, Brazil
  • Nucleo de Oncologia da Bahia
    Salvador, Brazil
  • Faculdade de Medicina do ABC
    Santo Andre, Brazil
  • Grupo Paulista de Oncologia Integrada Ltda
    Sao Paulo, Brazil
  • Hospital das Clinicas de Faculdade de Medicina da Universidade de Sao
    Sao Paulo, Brazil
  • Hospital do Cancer de Sao Paulo-AC Camargo
    Sao Paulo, Brazil
  • Hospital do Cancer de Sao Paulo-AC. Camargo
    Sao Paulo, Brazil
  • Instituto Brasileiro de Controle do Cancer-IBCC
    Sao Paulo, Brazil
  • Burgas, Bulgaria
  • Gabrovo, Bulgaria
  • Pleven, Bulgaria
  • Plovdiv, Bulgaria
  • Ruse, Bulgaria
  • Shumen, Bulgaria
  • Sofia, Bulgaria
  • Stara Zagora, Bulgaria
  • Varna, Bulgaria
  • Kingston, Ontario, Canada
  • Montreal General Hospital
    Montreal, Quebec H3G 1A4, Canada
  • Hopital du Sacre-Coeur de Montreal
    Montreal, Quebec H4J 1C5, Canada
  • Centre Hospitalier Universitaire de Montreal, Hopital Notre Dame
    Montreal, Canada
  • Thunder Bay Regional Health Science Centre Northwestern Ontario
    Thunder Bay, Canada
  • Nemocnice Ceske Budejovice, a.s.
    Ceske Budejovice, Czechia
  • Onkologicka Klinika, Fakutni Nemocnice
    Olomouc, Czechia
  • 1. LF UK, Ustav radiacnej onkologie
    Prague 8, Czechia
  • Krajska nemocnice T. Bati
    Zlin Poiters, Czechia
  • Centre Hospitalier La Roche sur Yon, CHD les Oudairies
    La Roche sur Yon, France
  • CHU de Poitiers, Service d'Oncologie Medicale
    Poitiers Cedex, France
  • Hopital Nord Saint-Etienne
    Saint Priest en Jarez, France
  • Augusta-Kranken-Anstalt, Klinik fur Hamatologie und Onkologie
    Bochum, Germany
  • Hamburg, Germany
  • Homburg, Germany
  • Universitatsfrauenklinik Magdeburg
    Magdeburg, Germany
  • Rostock, Germany
  • Patra, Greece
  • Gyor, Budapest, Hungary
  • Debrecen University
    Debrecen, Hungary
  • Debrecen, Hungary
  • Gyula, 5700, Hungary
  • Pecsi Tudomanyegyetem, Onkoterapias Intezet
    Pecs, Hungary
  • Szeged, Hungary
  • Veszprem, Hungary
  • Barzilai Medical Center
    Ashkelon, Israel
  • Soroka Medical Center
    Beer Sheva, Israel
  • Sharet Institute of Oncology
    Jerusalem, Israel
  • Meir Hospital, Sapir Medical Center
    Kfar Saba, Israel
  • Rabin Medical Center
    Petach Tikva, Israel
  • Kaplan Medical Center
    Rechovot, Israel
  • The Chaim Sheba Medical Center
    Tel Hashomer, Israel
  • Ancona, Italy
  • Unita Operativa de Oncologia
    Lugo, Italy

Showing the first 100 of 169 sites across 23 countries.

09

References and documents

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 27398025 ↗
  • Cortes 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 26567010 ↗
  • Kaufman 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 25605862 ↗
  • Twelves 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 27391598 ↗
  • Twelves 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 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 18, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00337103
Lead sponsor
Eisai Inc.
Responsible party
Sponsor
First posted
Jun 15, 2006
Start date
Sep 20, 2006
Primary completion
Mar 12, 2012
Completion
Dec 11, 2017
Results posted
Sep 30, 2013
Last update
Jun 18, 2020

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
View the source record on ClinicalTrials.gov ↗

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