A Study Comparing Eribulin Mesylate and Ixabepilone in Causing or Exacerbating Neuropathy in Participants With Advanced Breast Cancer

Sponsor
Eisai Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT00879086
Collaborator
(none)
104
50
2
61
2.1
0

Study Details

Study Description

Brief Summary

The purpose of this study in patients with advanced breast cancer is to compare the incidence and severity of neuropathy adverse events for the two treatment groups (eribulin versus ixabepilone) using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 3.0) grading.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
104 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II, Multicenter, Randomized, Open-Label Study Comparing Eribulin Mesylate and Ixabepilone in Causing or Exacerbating Neuropathy in Patients With Advanced Breast Cancer
Actual Study Start Date :
Mar 31, 2009
Actual Primary Completion Date :
Apr 30, 2013
Actual Study Completion Date :
Apr 30, 2014

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Eribulin mesylate

Drug: Eribulin Mesylate
E7389 (eribulin mesylate) given at a dose of 1.4 mg/m^2 as a 2 to 5 minute intravenous (IV) bolus on Days 1 and 8 of a 21-day cycle. The Treatment Phase will include six cycles. Patients may enter the Extension Phase for additional cycles following the sixth cycle of treatment.
Other Names:
  • E7389
  • Active Comparator: Ixabepilone

    Drug: Ixabepilone
    Ixabepilone given at a starting dose of 32 or 40 mg/m^2 (as per approved labeling) as a 3-hour IV infusion on Day 1 of a 21-day cycle. The Treatment Phase will include six cycles. Patients may enter the Extension Phase for additional cycles following the sixth cycle of treatment.

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants With Treatment-Emergent Neuropathy Adverse Events (AEs) [From administration of first dose up to approximately 5 years]

      Neuropathy AEs were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0 and coded according to the current version of the Medical Dictionary for Regulatory Activities (MedDRA). Neuropathy AEs included the broad list of preferred terms (PTs) defined in the Standard MedDRA Query for Neuropathy and the following additional PTs: neuropathy, hyperesthesia, painful response to normal stimuli, pallanesthesia, and allodynia. If the post-baseline maximum CTCAE grade of the combined term "neuropathy" was greater than the baseline maximum CTCAE grade of the combined term, then the event was considered as treatment emergent neuropathy adverse events per CTCAE grade. For a single participant, 1) a neuropathy AE occurring more than once during the study, whether defined with the same or different MedDRA PTs, was counted only once, 2) a neuropathy AE with different CTCAE grades had only the highest grade AE counted.

    Secondary Outcome Measures

    1. Percentage of Participants With an Incidence of Treatment-emergent Myalgia/Arthralgia [From administration of first dose up to approximately 5 years]

      The incidence rate of TE myalgia/arthralgia was calculated as the percent of participants with TE myalgia/arthralgia. A participant who had an arthralgia or myalgia AE more than once over the course of the study was counted only once in the incidence calculation for myalgia/arthralgia AEs. A participant who had myalgia/arthralgia AEs with different CTCAE grades was counted with the highest CTCAE grade over the course of the evaluation period. If the post-baseline CTCAE grade of the combined term "Myalgia/Arthralgia" was greater than the baseline maximum CTCAE grade of the combined term, the participant had TE myalgia/arthralgia. The 2-sided 95% confidence interval (CI) for incidence rate of TE myalgia/arthralgia was calculated using the Clopper-Pearson method (i.e., the exact method) for each treatment group.

    2. Change From Baseline in Vibration Perception Threshold (VPT) [Baseline, Treatment Phase: Cycles 2 to 6 (Day 1); Extension Phase: Cycle 9 Day 1, Cycle 12 Day 1, Cycle 15 Day 1 (Each Cycle length=21 days), End of Treatment, Post-treatment Follow-up, Worst Post-baseline result (Up to approximately 5 years)]

      The participant-reported questionnaire was used to compare the incidence and severity of neuropathy AEs. Sensory and motor scores were to be analyzed separately using a generalized linear model. Separate subgroup analyses were performed by each stratification variable. VPAT was measured using a Vibratron II device (Physitemp, Inc.) and a modified Two Alternative Forced Choice psychophysical algorithm. VPT was assessed on the ventral surface of the distal index finger (side opposite the nail), contralateral to the side of the mastectomy or primary disease and on the distal fleshy pad of both the right and left great toes (side opposite the nail). If the mastectomy was bilateral, the index finger on the side without axillary lymph node dissection was tested. Data ranged from 0 (invalid) to 20 vu. A lower VPT indicated a greater sensitivity.

    3. Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 1 (Sensory) [Baseline up to approximately 5 years]

      The PNQ consisted of 3 parts; Item 1 (sensory) measured numbness, pain, burning or tingling in hands or feet, Item 2 (motor) measured weakness in arms or legs, and Item 3 (activities) measured activities that interfered with daily life. The participant was told that there was no right or wrong answer and their answer should reflect how they currently felt since last completing the PNQ. Sensory scores were analyzed separately. Letter scores (A= none, B=mild, C=moderate, D=moderate to severe, and E=severe) for PNQ were converted to numeric scores A (none)=0, B (mild)=1, C (moderate)=2, D (moderate to severe)=3 and E (severe)=4). Total scores ranged from 0 (minimum severity) to 10 (maximum severity). Higher scores indicated greater severity. Neuropathy AEs that were sensory were evaluated with the PNQ Item 1 (sensory). Categories where no participant showed any shift from baseline to post-baseline for both the arms were not included in the presentation.

    4. Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 2 (Motor) [Baseline up to approximately 5 years]

      The PNQ consisted of 3 parts; Item 1 (sensory) measured numbness, pain, burning or tingling in hands or feet, Item 2 (motor) measured weakness in arms or legs, and Item 3 (activities) measured activities that interfered with daily life. The participant was told that there was no right or wrong answer and their answer should reflect how they currently felt since last completing the PNQ. Motor scores were analyzed separately. Letter scores (A= none, B=mild, C=moderate, D=moderate to severe, and E=severe) for PNQ were converted to numeric scores A (none)=0, B (mild)=1, C (moderate)=2, D (moderate to severe)=3 and E (severe)=4). Total scores ranged from 0 (minimum severity) to 10 (maximum severity). Higher scores indicated greater severity. Neuropathy AEs that were motor were evaluated with the PNQ Item 2 (motor). Categories where no participant showed any shift from baseline to post-baseline for both the arms were not included in the presentation.

    5. Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Composite Score [Baseline up to approximately 5 years]

      The PNQ consisted of 3 parts; Item 1 (sensory) measured numbness, pain, burning or tingling in hands or feet, Item 2 (motor) measured weakness in arms or legs, and Item 3 (activities) measured activities that interfered with daily life. Sensory scores, motor scores and composite scores were analyzed separately. For both item 1 and item 2, letter scores (A=none, B=mild, C=moderate, D=moderate to severe, and E=severe) for PNQ were converted to numeric scores A(none)=0, B(mild)=1, C(moderate)=2, D(moderate to severe)=3 and E (severe)=4. Total scores ranged from 0 (minimum severity) to 10 (maximum severity). Higher scores indicated greater severity. PNQ composite score was defined as the worst of Item 1 and Item 2 score. If neither Item 1 or item 2 score was D or E, but if a box was checked in Item 3, PNQ composite score would be D. Categories where no participant showed any shift from baseline to post-baseline for both the arms were not included in the presentation.

    6. Objective Response Rate (ORR) [From date of treatment start until disease progression (PD) (Up to approximately 5 years)]

      ORR was defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v.1.0 for target lesions assessed by magnetic resonance imaging and computed tomography and investigator assessment. Participants with unknown or missing responses were treated as non-responders. CR was defined as disappearance of all target lesions. PR was defined as at least a 30 percent (%) decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter. ORR=CR+PR, was presented with 2-sided 95% confidence interval (CI) by the method of Clopper-Pearson method for calculating the exact binomial intervals.

    7. Progression-Free Survival (PFS) [From date of treatment start until the date of PD or death from any cause (Up to approximately 5 years)]

      PFS was defined as the time from randomization until PD or death due to any cause as determined by the investigator. Disease progression per RECIST v1.0 was defined as at least a 20% relative increase and 5 millimeter absolute increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. The duration of PFS was calculated as the end date minus date of first drug plus 1. For participants who did not have an event (those lost to follow-up or who had not progressed at the date of data cut-off) PFS was censored. The median PFS and corresponding 95% CI was estimated for each treatment group using the Kaplan-Meier method.

    8. Clinical Benefit Rate (CBR) [From date of treatment start until PD or death from any cause, whichever occurred first (Up to approximately 5 years)]

      CBR was defined as the number of participants (CR + PR + stable disease (SD) greater than or equal to 6 months) divided by the number of participants in the analysis population. The 95% CI was generated for the clinical benefit rate for each treatment group, and it was based on the Clopper-Pearson method for calculating the exact binomial intervals.

    9. Duration of Response (DoR) [From date of first CR or PR until the first documentation of PD or date of death (Up to approximately 5 years)]

      DoR was defined as the time from first documented CR or PR until PD or death from any cause. It was measured from the time that measurement criteria were met for CR or PR (whichever status was recorded first) until the first date that recurrent or PD was objectively documented. It was defined for participants with a confirmed CR or a confirmed PR. Participants without progressive disease or death were censored. Median duration and 95% CI of the median were estimated for each treatment group, using the Kaplan-Meier method.

    10. Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Eribulin and Ixabepilone [For each participant, from the first dose till 42 days after the last dose of study treatment (Up to approximately 5 years)]

      General safety was assessed by monitoring all TEAEs and SAEs. TEAEs were reported at a frequency of 0% or greater in the study population.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion criteria:
    1. Female subjects with confirmed locally recurrent or metastatic carcinoma of the breast who have received prior taxane therapy and at least one prior cytotoxic chemotherapy regimen for advanced disease.
    Exclusion criteria:
    1. Subjects who have received prior ixabepilone therapy.

    2. Subjects with prior participation in an eribulin clinical study, even if not assigned to eribulin treatment.

    3. Subjects with pre-existing neuropathy Grade greater than or equal to 2.

    4. Subjects with a history of diabetes mellitus Type 1 or 2.

    5. Subjects with bilateral mastectomy which included bilateral axillary lymph node dissection.

    6. Subjects with missing digits required for vibration assessment.

    7. Subjects with any other concurrent diseases or conditions that would be expected to interfere with neuropathy assessments, which may include vitamin deficiency, sequelae of cerebrovascular disease, thyroid insufficiency, lumbar or cervical radiculopathy, or alcoholic or inflammatory neuropathy.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Northern AZ Hematology and Oncology Associates Sedona Arizona United States 86336
    2 Healing Hands Oncology and Medical Care Hawthorne California United States 90250
    3 University of Southern California Los Angeles California United States 90033
    4 Comprehensive Cancer Center Palm Springs California United States 92262
    5 Comprehensive Cancer Care Specialist of Boca Boca Raton Florida United States 33428
    6 Robert R. Carroll, MD, PA Gainesville Florida United States 32605
    7 Hematology Oncology Associates Lake Worth Florida United States 33461
    8 Medical Specialists of the Palm Beaches Lake Worth Florida United States 33467
    9 Ocala Oncology Center Ocala Florida United States 34471
    10 Hematology Oncology Associates of Treasure Coast Port Saint Lucie Florida United States 34952
    11 Oncology and Hematology Associates of West Broward Tamarac Florida United States 33321
    12 Hematology Oncology Associates of Illinois Chicago Illinois United States 60611
    13 Decatur Memorial Hospital Decatur Illinois United States 62526
    14 Central Indiana Cancer Centers Indianapolis Indiana United States 46219
    15 Heartland Oncology Hematology Council Bluffs Iowa United States 51503
    16 Hematology and Oncology Specialists Marrero Louisiana United States 70072
    17 Metairie Institute of Comprehensive Health Metairie Louisiana United States 70006
    18 Hematology and Oncology Specialists New Orleans Louisiana United States 70115
    19 Maryland Oncology Hematology, PA Columbia Maryland United States 21044
    20 Washington County Hospital Hagerstown Maryland United States 21740
    21 Josephine Ford Cancer Center Brownstown Michigan United States 48183
    22 Henry Ford Medical Center-Fairlane Dearborn Michigan United States 48126
    23 Henry Ford Health Systems Detroit Michigan United States 48202
    24 Henry Ford Medical Center Farmington West Bloomfield Michigan United States 48322
    25 Summit Medical Group Berkeley Heights New Jersey United States 7922
    26 Joan Knechel Cancer Center Mount Arlington New Jersey United States 7856
    27 Montefiore Medical Center Bronx New York United States 10461
    28 Queens Cancer Center of Queens Hospital Jamaica New York United States 11432
    29 Saint Vincent's Comprehensive Cancer Center New York New York United States 10011
    30 Weil Cornell Breast Center New York New York United States 10065
    31 Charleston Hematology Oncology Associates PA Charleston North Carolina United States 29403
    32 Cancer Center of North Carolina Raleigh North Carolina United States 27607
    33 Northwest Cancer Specialists Rose Quarter Portland Oregon United States 97227
    34 Northwest Cancer Specialists Hoyt Portland Oregon United States
    35 Northwest Cancer Specialists Tualatin Oregon United States 97062
    36 Lone Star Oncology Austin Texas United States 78759
    37 South Texas Institute of Cancer Corpus Christi Texas United States 78405
    38 Northwest Cancer Center Corpus Christi Texas United States 78410
    39 Texas Oncology-Sammons Cancer Center Dallas Texas United States 75246
    40 Texas Cancer Center at Medical City Dallas Texas United States
    41 Texas Oncology, PA Dallas Texas United States
    42 Texas Oncology, PA Bedford Houston Texas United States 76033
    43 Texas Oncology, PA Houston Texas United States 77024
    44 North Texas Regional Cancer Center Plano Texas United States
    45 Tyler Cancer Center Tyler Texas United States 75702
    46 Northern Utah Associates Ogden Utah United States 84403
    47 Virginia Oncology Associates Newport News Virginia United States 23606
    48 Virginia Oncology Associates Norfolk Virginia United States 23502
    49 Northwest Cancer Specialist Vancouver Vancouver Washington United States 98684
    50 Northwest Cancer Care Specialists, P.C. Vancouver Washington United States 98686

    Sponsors and Collaborators

    • Eisai Inc.

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Eisai Inc.
    ClinicalTrials.gov Identifier:
    NCT00879086
    Other Study ID Numbers:
    • E7389-G000-209
    First Posted:
    Apr 9, 2009
    Last Update Posted:
    Dec 1, 2021
    Last Verified:
    Oct 1, 2021
    Keywords provided by Eisai Inc.
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 127 participants were screened. Of these, 104 participants were enrolled and randomized into the study and 23 participants were screen failures (19 failed to meet entrance criteria, 3 failed due to other reason, and 1 failed due to consent withdrawal).
    Arm/Group Title Eribulin Mesylate Ixabepilone
    Arm/Group Description Eribulin mesylate was given at a dose of 1.4 milligram per square meter (mg/m^2) as a 2 to 5 minute intravenous (IV) bolus on Days 1 and 8 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks). Ixabepilone was given at a starting dose of 32 or 40 mg/m^2 (as per approved labeling) as a 3-hour IV infusion on Day 1 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).
    Period Title: Overall Study
    STARTED 52 52
    Safety Analysis Set (SAS) 51 50
    COMPLETED 0 0
    NOT COMPLETED 52 52

    Baseline Characteristics

    Arm/Group Title Eribulin Mesylate Ixabepilone Total
    Arm/Group Description Eribulin mesylate was given at a dose of 1.4 mg/m^2 as a 2 to 5 minute IV bolus on Days 1 and 8 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks). Ixabepilone was given at a starting dose of 32 or 40 mg/m^2 (as per approved labeling) as a 3-hour IV infusion on Day 1 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks). Total of all reporting groups
    Overall Participants 51 50 101
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    52.2
    (9.83)
    56.9
    (10.68)
    54.5
    (10.49)
    Sex/Gender, Customized (Count of Participants)
    Female
    51
    100%
    50
    100%
    101
    100%
    Male
    0
    0%
    0
    0%
    0
    0%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants With Treatment-Emergent Neuropathy Adverse Events (AEs)
    Description Neuropathy AEs were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0 and coded according to the current version of the Medical Dictionary for Regulatory Activities (MedDRA). Neuropathy AEs included the broad list of preferred terms (PTs) defined in the Standard MedDRA Query for Neuropathy and the following additional PTs: neuropathy, hyperesthesia, painful response to normal stimuli, pallanesthesia, and allodynia. If the post-baseline maximum CTCAE grade of the combined term "neuropathy" was greater than the baseline maximum CTCAE grade of the combined term, then the event was considered as treatment emergent neuropathy adverse events per CTCAE grade. For a single participant, 1) a neuropathy AE occurring more than once during the study, whether defined with the same or different MedDRA PTs, was counted only once, 2) a neuropathy AE with different CTCAE grades had only the highest grade AE counted.
    Time Frame From administration of first dose up to approximately 5 years

    Outcome Measure Data

    Analysis Population Description
    SAS included all randomized participants who received at least one dose of study medication and who had at least one safety assessment following the first dose of study medication.
    Arm/Group Title Eribulin Mesylate Ixabepilone
    Arm/Group Description Eribulin mesylate was given at a dose of 1.4 mg/m^2 as a 2 to 5 minute IV bolus on Days 1 and 8 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks). Ixabepilone was given at a starting dose of 32 or 40 mg/m^2 (as per approved labeling) as a 3-hour IV infusion on Day 1 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).
    Measure Participants 51 50
    Number (95% Confidence Interval) [Percentage of participants]
    33.3
    65.3%
    50.0
    100%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Eribulin Mesylate, Ixabepilone
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value =0.0941
    Comments The two treatment groups were compared, controlling for baseline pre-existing neuropathy (CTCAE Grade 0 or 1) and number of prior chemotherapy regimens (less than or equal to 3 or greater than 3), with both covariates included as binary variables.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -16.7
    Confidence Interval (2-Sided) 95%
    -36.1 to 2.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Extended Mantel-Haenszel test statistics with stratification adjustment for pre-existing baseline neuropathy (CTCAE Grade 0 or 1) and number of prior chemotherapy regimens (greater than or equal to 3 or greater than 3)
    2. Secondary Outcome
    Title Percentage of Participants With an Incidence of Treatment-emergent Myalgia/Arthralgia
    Description The incidence rate of TE myalgia/arthralgia was calculated as the percent of participants with TE myalgia/arthralgia. A participant who had an arthralgia or myalgia AE more than once over the course of the study was counted only once in the incidence calculation for myalgia/arthralgia AEs. A participant who had myalgia/arthralgia AEs with different CTCAE grades was counted with the highest CTCAE grade over the course of the evaluation period. If the post-baseline CTCAE grade of the combined term "Myalgia/Arthralgia" was greater than the baseline maximum CTCAE grade of the combined term, the participant had TE myalgia/arthralgia. The 2-sided 95% confidence interval (CI) for incidence rate of TE myalgia/arthralgia was calculated using the Clopper-Pearson method (i.e., the exact method) for each treatment group.
    Time Frame From administration of first dose up to approximately 5 years

    Outcome Measure Data

    Analysis Population Description
    SAS included all randomized participants who received at least one dose of study medication and who had at least one safety assessment following the first dose of study medication.
    Arm/Group Title Eribulin Mesylate Ixabepilone
    Arm/Group Description Eribulin mesylate was given at a dose of 1.4 mg/m^2 as a 2 to 5 minute IV bolus on Days 1 and 8 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks). Ixabepilone was given at a starting dose of 32 or 40 mg/m^2 (as per approved labeling) as a 3-hour IV infusion on Day 1 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).
    Measure Participants 51 50
    Number (95% Confidence Interval) [Percentage of participants]
    19.6
    38.4%
    38.0
    76%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Eribulin Mesylate, Ixabepilone
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0492
    Comments Controlled for baseline pre-existing neuropathy (CTCAE Grade 0 or 1) and number of prior chemotherapy regimens (greater than or equal to 3 or greater than 3), with both covariates included as binary variables.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Difference in proportions
    Estimated Value -18.4
    Confidence Interval (2-Sided) 95%
    -36.0 to -0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Extended Mantel-Haenszel test statistics with stratification adjustment for pre-existing baseline neuropathy (CTCAE Grade 0 or 1) and number of prior chemotherapy regimens (greater than or equal to 3 or greater than 3)
    3. Secondary Outcome
    Title Change From Baseline in Vibration Perception Threshold (VPT)
    Description The participant-reported questionnaire was used to compare the incidence and severity of neuropathy AEs. Sensory and motor scores were to be analyzed separately using a generalized linear model. Separate subgroup analyses were performed by each stratification variable. VPAT was measured using a Vibratron II device (Physitemp, Inc.) and a modified Two Alternative Forced Choice psychophysical algorithm. VPT was assessed on the ventral surface of the distal index finger (side opposite the nail), contralateral to the side of the mastectomy or primary disease and on the distal fleshy pad of both the right and left great toes (side opposite the nail). If the mastectomy was bilateral, the index finger on the side without axillary lymph node dissection was tested. Data ranged from 0 (invalid) to 20 vu. A lower VPT indicated a greater sensitivity.
    Time Frame Baseline, Treatment Phase: Cycles 2 to 6 (Day 1); Extension Phase: Cycle 9 Day 1, Cycle 12 Day 1, Cycle 15 Day 1 (Each Cycle length=21 days), End of Treatment, Post-treatment Follow-up, Worst Post-baseline result (Up to approximately 5 years)

    Outcome Measure Data

    Analysis Population Description
    SAS included all randomized participants who received at least one dose of study medication and who had at least one safety assessment following the first dose of study medication. Here "number analyzed" signifies participants who were evaluable for this outcome measure at given time points.
    Arm/Group Title Eribulin Mesylate Ixabepilone
    Arm/Group Description Eribulin mesylate was given at a dose of 1.4 mg/m^2 as a 2 to 5 minute IV bolus on Days 1 and 8 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks). Ixabepilone was given at a starting dose of 32 or 40 mg/m^2 (as per approved labeling) as a 3-hour IV infusion on Day 1 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).
    Measure Participants 51 50
    Index Finger, Baseline
    1.50
    (1.117)
    1.96
    (1.373)
    Index Finger, Cycle 2 (Day 1)
    0.13
    (1.196)
    -0.09
    (1.641)
    Index Finger, Cycle 3 (Day 1)
    0.31
    (0.478)
    -0.22
    (1.762)
    Index Finger, Cycle 4 (Day 1)
    0.67
    (1.218)
    -0.14
    (1.588)
    Index Finger, Cycle 5 (Day 1)
    0.93
    (1.291)
    0.10
    (1.828)
    Index Finger, Cycle 6 (Day 1)
    1.86
    (2.515)
    -0.07
    (2.213)
    Index Finger, Cycle 9 (Day 1)
    1.94
    (2.221)
    0.35
    (1.144)
    Index Finger, Cycle 12 (Day 1)
    0.50
    (0.816)
    0.65
    (0.354)
    Index Finger, Cycle 15 (Day 1)
    0.90
    (0.906)
    1.30
    (NA)
    Index finger, End of Treatment
    1.23
    (2.108)
    0.35
    (1.388)
    Index finger, Post-treatment follow-up
    1.34
    (1.727)
    0.58
    (0.991)
    Index finger, Worst post-baseline result
    1.95
    (2.491)
    0.67
    (1.721)
    Great toe, Baseline
    5.22
    (2.393)
    6.60
    (3.525)
    Great toe, Cycle 2 (Day 1)
    0.15
    (1.760)
    0.08
    (1.988)
    Great toe, Cycle 3 (Day 1)
    0.49
    (2.110)
    0.20
    (2.589)
    Great toe, Cycle 4 (Day 1)
    0.89
    (2.037)
    0.82
    (3.679)
    Great toe, Cycle 5 (Day 1)
    1.08
    (1.899)
    0.54
    (3.645)
    Great toe, Cycle 6 (Day 1)
    2.28
    (2.873)
    0.39
    (3.371)
    Great toe, Cycle 9 (Day 1)
    2.69
    (3.711)
    1.34
    (2.417)
    Great toe, Cycle 12 (Day 1)
    1.23
    (2.992)
    5.35
    (0.636)
    Great toe, Cycle 15 (Day 1)
    1.12
    (3.070)
    3.40
    Great toe, End of treatment
    1.39
    (2.208)
    1.71
    (2.682)
    Great toe, Post-treatment follow-up
    3.34
    (2.422)
    1.53
    (3.371)
    Great toe, Worst post-baseline results
    2.39
    (2.762)
    2.16
    (2.916)
    4. Secondary Outcome
    Title Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 1 (Sensory)
    Description The PNQ consisted of 3 parts; Item 1 (sensory) measured numbness, pain, burning or tingling in hands or feet, Item 2 (motor) measured weakness in arms or legs, and Item 3 (activities) measured activities that interfered with daily life. The participant was told that there was no right or wrong answer and their answer should reflect how they currently felt since last completing the PNQ. Sensory scores were analyzed separately. Letter scores (A= none, B=mild, C=moderate, D=moderate to severe, and E=severe) for PNQ were converted to numeric scores A (none)=0, B (mild)=1, C (moderate)=2, D (moderate to severe)=3 and E (severe)=4). Total scores ranged from 0 (minimum severity) to 10 (maximum severity). Higher scores indicated greater severity. Neuropathy AEs that were sensory were evaluated with the PNQ Item 1 (sensory). Categories where no participant showed any shift from baseline to post-baseline for both the arms were not included in the presentation.
    Time Frame Baseline up to approximately 5 years

    Outcome Measure Data

    Analysis Population Description
    SAS included all randomized participants who received at least one dose of study medication and who had at least one safety assessment following the first dose of study medication. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.
    Arm/Group Title Eribulin Mesylate Ixabepilone
    Arm/Group Description Eribulin mesylate was given at a dose of 1.4 mg/m^2 as a 2 to 5 minute IV bolus on Days 1 and 8 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks). Ixabepilone was given at a starting dose of 32 or 40 mg/m^2 (as per approved labeling) as a 3-hour IV infusion on Day 1 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).
    Measure Participants 48 46
    A (Baseline) to A (Worst Post-baseline)
    8
    15.7%
    7
    14%
    A (Baseline) to B (Worst Post-baseline)
    9
    17.6%
    3
    6%
    A (Baseline) to C (Worst Post-baseline)
    5
    9.8%
    4
    8%
    A (Baseline) to D (Worst Post-baseline)
    2
    3.9%
    4
    8%
    A (Baseline) to E (Worst Post-baseline)
    0
    0%
    1
    2%
    B (Baseline) to A (Worst Post-baseline)
    1
    2%
    1
    2%
    B (Baseline) to B (Worst Post-baseline)
    5
    9.8%
    4
    8%
    B (Baseline) to C (Worst Post-baseline)
    2
    3.9%
    8
    16%
    B (Baseline) to D (Worst Post-baseline)
    9
    17.6%
    5
    10%
    B (Baseline) to E (Worst Post-baseline)
    1
    2%
    0
    0%
    C (Baseline) to B (Worst Post-baseline)
    0
    0%
    1
    2%
    C (Baseline) to C (Worst Post-baseline)
    3
    5.9%
    4
    8%
    C (Baseline) to D (Worst Post-baseline)
    2
    3.9%
    3
    6%
    D (Baseline) to D (Worst Post-baseline)
    1
    2%
    1
    2%
    5. Secondary Outcome
    Title Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 2 (Motor)
    Description The PNQ consisted of 3 parts; Item 1 (sensory) measured numbness, pain, burning or tingling in hands or feet, Item 2 (motor) measured weakness in arms or legs, and Item 3 (activities) measured activities that interfered with daily life. The participant was told that there was no right or wrong answer and their answer should reflect how they currently felt since last completing the PNQ. Motor scores were analyzed separately. Letter scores (A= none, B=mild, C=moderate, D=moderate to severe, and E=severe) for PNQ were converted to numeric scores A (none)=0, B (mild)=1, C (moderate)=2, D (moderate to severe)=3 and E (severe)=4). Total scores ranged from 0 (minimum severity) to 10 (maximum severity). Higher scores indicated greater severity. Neuropathy AEs that were motor were evaluated with the PNQ Item 2 (motor). Categories where no participant showed any shift from baseline to post-baseline for both the arms were not included in the presentation.
    Time Frame Baseline up to approximately 5 years

    Outcome Measure Data

    Analysis Population Description
    SAS included all randomized participants who received at least one dose of study medication and who had at least one safety assessment following the first dose of study medication. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.
    Arm/Group Title Eribulin Mesylate Ixabepilone
    Arm/Group Description Eribulin mesylate was given at a dose of 1.4 mg/m^2 as a 2 to 5 minute IV bolus on Days 1 and 8 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks). Ixabepilone was given at a starting dose of 32 or 40 mg/m^2 (as per approved labeling) as a 3-hour IV infusion on Day 1 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).
    Measure Participants 48 46
    A (Baseline) to A (Worst Post-baseline)
    8
    15.7%
    12
    24%
    A (Baseline) to B (Worst Post-baseline)
    12
    23.5%
    3
    6%
    A (Baseline) to C (Worst Post-baseline)
    8
    15.7%
    6
    12%
    A (Baseline) to D (Worst Post-baseline)
    2
    3.9%
    7
    14%
    A (Baseline) to E (Worst Post-baseline)
    0
    0%
    1
    2%
    B (Baseline) to B (Worst Post-baseline)
    5
    9.8%
    5
    10%
    B (Baseline) to C (Worst Post-baseline)
    4
    7.8%
    2
    4%
    B (Baseline) to D (Worst Post-baseline)
    4
    7.8%
    4
    8%
    C (Baseline) to C (Worst Post-baseline)
    0
    0%
    1
    2%
    C (Baseline) to D (Worst Post-baseline)
    0
    0%
    4
    8%
    D (Baseline) to A (Worst Post-baseline)
    1
    2%
    0
    0%
    D (Baseline) to D (Worst Post-baseline)
    3
    5.9%
    0
    0%
    D (Baseline) to E (Worst Post-baseline)
    1
    2%
    1
    2%
    6. Secondary Outcome
    Title Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Composite Score
    Description The PNQ consisted of 3 parts; Item 1 (sensory) measured numbness, pain, burning or tingling in hands or feet, Item 2 (motor) measured weakness in arms or legs, and Item 3 (activities) measured activities that interfered with daily life. Sensory scores, motor scores and composite scores were analyzed separately. For both item 1 and item 2, letter scores (A=none, B=mild, C=moderate, D=moderate to severe, and E=severe) for PNQ were converted to numeric scores A(none)=0, B(mild)=1, C(moderate)=2, D(moderate to severe)=3 and E (severe)=4. Total scores ranged from 0 (minimum severity) to 10 (maximum severity). Higher scores indicated greater severity. PNQ composite score was defined as the worst of Item 1 and Item 2 score. If neither Item 1 or item 2 score was D or E, but if a box was checked in Item 3, PNQ composite score would be D. Categories where no participant showed any shift from baseline to post-baseline for both the arms were not included in the presentation.
    Time Frame Baseline up to approximately 5 years

    Outcome Measure Data

    Analysis Population Description
    SAS included all randomized participants who received at least one dose of study medication and who had at least one safety assessment following the first dose of study medication. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.
    Arm/Group Title Eribulin Mesylate Ixabepilone
    Arm/Group Description Eribulin mesylate was given at a dose of 1.4 mg/m^2 as a 2 to 5 minute IV bolus on Days 1 and 8 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks). Ixabepilone was given at a starting dose of 32 or 40 mg/m^2 (as per approved labeling) as a 3-hour IV infusion on Day 1 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).
    Measure Participants 48 46
    A (Baseline) to A (Worst Post-baseline)
    3
    5.9%
    5
    10%
    A (Baseline) to B (Worst Post-baseline)
    6
    11.8%
    1
    2%
    A (Baseline) to C (Worst Post-baseline)
    5
    9.8%
    2
    4%
    A (Baseline) to D (Worst Post-baseline)
    2
    3.9%
    5
    10%
    A (Baseline) to E (Worst Post-baseline)
    0
    0%
    1
    2%
    B (Baseline) to A (Worst Post-baseline)
    0
    0%
    1
    2%
    B (Baseline) to B (Worst Post-baseline)
    5
    9.8%
    6
    12%
    B (Baseline) to C (Worst Post-baseline)
    5
    9.8%
    6
    12%
    B (Baseline) to D (Worst Post-baseline)
    9
    17.6%
    6
    12%
    C (Baseline) to C (Worst Post-baseline)
    2
    3.9%
    0
    0%
    C (Baseline) to D (Worst Post-baseline)
    1
    2%
    3
    6%
    D (Baseline) to A (Worst Post-baseline)
    1
    2%
    0
    0%
    D (Baseline) to C (Worst Post-baseline)
    0
    0%
    2
    4%
    D (Baseline) to D (Worst Post-baseline)
    7
    13.7%
    7
    14%
    D (Baseline) to E (Worst Post-baseline)
    2
    3.9%
    1
    2%
    7. Secondary Outcome
    Title Objective Response Rate (ORR)
    Description ORR was defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v.1.0 for target lesions assessed by magnetic resonance imaging and computed tomography and investigator assessment. Participants with unknown or missing responses were treated as non-responders. CR was defined as disappearance of all target lesions. PR was defined as at least a 30 percent (%) decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter. ORR=CR+PR, was presented with 2-sided 95% confidence interval (CI) by the method of Clopper-Pearson method for calculating the exact binomial intervals.
    Time Frame From date of treatment start until disease progression (PD) (Up to approximately 5 years)

    Outcome Measure Data

    Analysis Population Description
    Full analysis set (FAS) included all randomized participants.
    Arm/Group Title Eribulin Mesylate Ixabepilone
    Arm/Group Description Eribulin mesylate was given at a dose of 1.4 mg/m^2 as a 2 to 5 minute IV bolus on Days 1 and 8 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks). Ixabepilone was given at a starting dose of 32 or 40 mg/m^2 (as per approved labeling) as a 3-hour IV infusion on Day 1 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).
    Measure Participants 52 52
    Number (95% Confidence Interval) [Percentage of participants]
    15.4
    30.2%
    5.8
    11.6%
    8. Secondary Outcome
    Title Progression-Free Survival (PFS)
    Description PFS was defined as the time from randomization until PD or death due to any cause as determined by the investigator. Disease progression per RECIST v1.0 was defined as at least a 20% relative increase and 5 millimeter absolute increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. The duration of PFS was calculated as the end date minus date of first drug plus 1. For participants who did not have an event (those lost to follow-up or who had not progressed at the date of data cut-off) PFS was censored. The median PFS and corresponding 95% CI was estimated for each treatment group using the Kaplan-Meier method.
    Time Frame From date of treatment start until the date of PD or death from any cause (Up to approximately 5 years)

    Outcome Measure Data

    Analysis Population Description
    FAS analysis set included all randomized participants.
    Arm/Group Title Eribulin Mesylate Ixabepilone
    Arm/Group Description Eribulin mesylate was given at a dose of 1.4 mg/m^2 as a 2 to 5 minute IV bolus on Days 1 and 8 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks). Ixabepilone was given at a starting dose of 32 or 40 mg/m^2 (as per approved labeling) as a 3-hour IV infusion on Day 1 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).
    Measure Participants 52 52
    Median (95% Confidence Interval) [Days]
    104
    95
    9. Secondary Outcome
    Title Clinical Benefit Rate (CBR)
    Description CBR was defined as the number of participants (CR + PR + stable disease (SD) greater than or equal to 6 months) divided by the number of participants in the analysis population. The 95% CI was generated for the clinical benefit rate for each treatment group, and it was based on the Clopper-Pearson method for calculating the exact binomial intervals.
    Time Frame From date of treatment start until PD or death from any cause, whichever occurred first (Up to approximately 5 years)

    Outcome Measure Data

    Analysis Population Description
    FAS analysis set included all randomized participants.
    Arm/Group Title Eribulin Mesylate Ixabepilone
    Arm/Group Description Eribulin mesylate was given at a dose of 1.4 mg/m^2 as a 2 to 5 minute IV bolus on Days 1 and 8 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks). Ixabepilone was given at a starting dose of 32 or 40 mg/m^2 (as per approved labeling) as a 3-hour IV infusion on Day 1 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).
    Measure Participants 52 52
    Number (95% Confidence Interval) [Percentage of participants]
    26.9
    52.7%
    21.2
    42.4%
    10. Secondary Outcome
    Title Duration of Response (DoR)
    Description DoR was defined as the time from first documented CR or PR until PD or death from any cause. It was measured from the time that measurement criteria were met for CR or PR (whichever status was recorded first) until the first date that recurrent or PD was objectively documented. It was defined for participants with a confirmed CR or a confirmed PR. Participants without progressive disease or death were censored. Median duration and 95% CI of the median were estimated for each treatment group, using the Kaplan-Meier method.
    Time Frame From date of first CR or PR until the first documentation of PD or date of death (Up to approximately 5 years)

    Outcome Measure Data

    Analysis Population Description
    FAS analysis set included all randomized participants. Number of participants analyzed who had CR or PR.
    Arm/Group Title Eribulin Mesylate Ixabepilone
    Arm/Group Description Eribulin mesylate was given at a dose of 1.4 mg/m^2 as a 2 to 5 minute IV bolus on Days 1 and 8 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks). Ixabepilone was given at a starting dose of 32 or 40 mg/m^2 (as per approved labeling) as a 3-hour IV infusion on Day 1 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).
    Measure Participants 8 3
    Median (95% Confidence Interval) [Days]
    169
    NA
    11. Secondary Outcome
    Title Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Eribulin and Ixabepilone
    Description General safety was assessed by monitoring all TEAEs and SAEs. TEAEs were reported at a frequency of 0% or greater in the study population.
    Time Frame For each participant, from the first dose till 42 days after the last dose of study treatment (Up to approximately 5 years)

    Outcome Measure Data

    Analysis Population Description
    SAS included all randomized participants who received at least one dose of study medication and who had at least one safety assessment following the first dose of study medication.
    Arm/Group Title Eribulin Mesylate Ixabepilone
    Arm/Group Description Eribulin mesylate was given at a dose of 1.4 mg/m^2 as a 2 to 5 minute IV bolus on Days 1 and 8 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks). Ixabepilone was given at a starting dose of 32 or 40 mg/m^2 (as per approved labeling) as a 3-hour IV infusion on Day 1 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).
    Measure Participants 51 50
    TEAEs
    100.0
    196.1%
    100.0
    200%
    SAEs
    37.3
    73.1%
    34.0
    68%

    Adverse Events

    Time Frame For each participant, from the first dose till 42 days after the last dose of study treatment (Up to approximately 5 years)
    Adverse Event Reporting Description Treatment-emergent adverse events were reported. All adverse events were graded using National Cancer Institute Common Terminology Criteria (NCI CTCAE) version 3.0. The SAS included all randomized participants who received at least one dose of study medication and who had at least one safety assessment following the first dose of study medication. Of 104 participants randomized into the study, 3 did not receive treatment, 1 in the E7389 Treatment Group and 2 in the Ixabepilone Treatment Group.
    Arm/Group Title Eribulin Mesylate Ixabepilone
    Arm/Group Description Eribulin mesylate was given at a dose of 1.4 mg/m^2 as a 2 to 5 minute IV bolus on Days 1 and 8 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks). Ixabepilone was given at a starting dose of 32 or 40 mg/m^2 (as per approved labeling) as a 3-hour IV infusion on Day 1 of a 21-day cycle during the Treatment and Extension Phases. The Treatment Phase included six cycles. Following the sixth cycle of the Treatment Phase, participants who demonstrated clinical benefit could continue treatment during the Extension Phase for an indefinite number of cycles for as long as clinical benefit was sustained (up to 211 weeks).
    All Cause Mortality
    Eribulin Mesylate Ixabepilone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/51 (3.9%) 2/50 (4%)
    Serious Adverse Events
    Eribulin Mesylate Ixabepilone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 19/51 (37.3%) 17/50 (34%)
    Blood and lymphatic system disorders
    Febrile neutropenia 6/51 (11.8%) 0/50 (0%)
    Anaemia 1/51 (2%) 1/50 (2%)
    Leukopenia 1/51 (2%) 0/50 (0%)
    Neutropenia 1/51 (2%) 1/50 (2%)
    Thrombocytopenia 0/51 (0%) 1/50 (2%)
    Cardiac disorders
    Pericarditis 1/51 (2%) 0/50 (0%)
    Atrial flutter 0/51 (0%) 1/50 (2%)
    Cardiac failure congestive 0/51 (0%) 1/50 (2%)
    Eye disorders
    Visual impairment 0/51 (0%) 1/50 (2%)
    Gastrointestinal disorders
    Dysphagia 1/51 (2%) 0/50 (0%)
    Abdominal pain 0/51 (0%) 1/50 (2%)
    General disorders
    Chills 1/51 (2%) 0/50 (0%)
    Mucosal inflammation 1/51 (2%) 1/50 (2%)
    Pain 1/51 (2%) 1/50 (2%)
    Pyrexia 1/51 (2%) 1/50 (2%)
    Chest pain 0/51 (0%) 1/50 (2%)
    Non-cardiac chest pain 0/51 (0%) 1/50 (2%)
    Hepatobiliary disorders
    Hepatic failure 0/51 (0%) 1/50 (2%)
    Infections and infestations
    Sepsis 2/51 (3.9%) 0/50 (0%)
    Device related infection 1/51 (2%) 0/50 (0%)
    Pneumonia 1/51 (2%) 0/50 (0%)
    Cellulitis 0/51 (0%) 1/50 (2%)
    Injury, poisoning and procedural complications
    Lower limb fracture 1/51 (2%) 0/50 (0%)
    Radiation pneumonitis 1/51 (2%) 0/50 (0%)
    Investigations
    Haemoglobin decreased 0/51 (0%) 1/50 (2%)
    Metabolism and nutrition disorders
    Dehydration 1/51 (2%) 0/50 (0%)
    Hypovolaemia 1/51 (2%) 0/50 (0%)
    Hypercalcaemia 0/51 (0%) 2/50 (4%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/51 (2%) 0/50 (0%)
    Myalgia / Arthralgia 1/51 (2%) 1/50 (2%)
    Intervertebral disc protrusion 0/51 (0%) 1/50 (2%)
    Myalgia 0/51 (0%) 1/50 (2%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Metastases to central nervous system 2/51 (3.9%) 0/50 (0%)
    Malignant neoplasm progression 2/51 (3.9%) 0/50 (0%)
    Malignant pleural effusion 0/51 (0%) 1/50 (2%)
    Metastases to meninges 0/51 (0%) 1/50 (2%)
    Nervous system disorders
    Dizziness 1/51 (2%) 0/50 (0%)
    Reversible posterior leukoencephalopathy syndrome 1/51 (2%) 0/50 (0%)
    Convulsion 0/51 (0%) 1/50 (2%)
    Peripheral Neuropathy 0/51 (0%) 1/50 (2%)
    Peripheral sensory neuropathy 0/51 (0%) 1/50 (2%)
    Psychiatric disorders
    Confusional state 1/51 (2%) 0/50 (0%)
    Mental status changes 1/51 (2%) 0/50 (0%)
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism 1/51 (2%) 0/50 (0%)
    Asthma 0/51 (0%) 1/50 (2%)
    Dyspnoea 0/51 (0%) 1/50 (2%)
    Pleural effusion 0/51 (0%) 1/50 (2%)
    Other (Not Including Serious) Adverse Events
    Eribulin Mesylate Ixabepilone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 51/51 (100%) 50/50 (100%)
    Blood and lymphatic system disorders
    Neutropenia 24/51 (47.1%) 14/50 (28%)
    Anaemia 13/51 (25.5%) 10/50 (20%)
    Febrile neutropenia 8/51 (15.7%) 1/50 (2%)
    Thrombocytopenia 6/51 (11.8%) 7/50 (14%)
    Leukopenia 3/51 (5.9%) 3/50 (6%)
    Eye disorders
    Lacrimation increased 4/51 (7.8%) 0/50 (0%)
    Gastrointestinal disorders
    Nausea 23/51 (45.1%) 27/50 (54%)
    Diarrhoea 12/51 (23.5%) 12/50 (24%)
    Vomiting 12/51 (23.5%) 15/50 (30%)
    Constipation 11/51 (21.6%) 10/50 (20%)
    Dry mouth 5/51 (9.8%) 1/50 (2%)
    Abdominal pain 4/51 (7.8%) 9/50 (18%)
    Abdominal pain upper 4/51 (7.8%) 0/50 (0%)
    Ascites 3/51 (5.9%) 0/50 (0%)
    Dyspepsia 3/51 (5.9%) 6/50 (12%)
    Gastrooesophageal reflux disease 3/51 (5.9%) 0/50 (0%)
    Stomatitis 3/51 (5.9%) 5/50 (10%)
    Abdominal pain lower 0/51 (0%) 4/50 (8%)
    General disorders
    Fatigue 19/51 (37.3%) 27/50 (54%)
    Fatigue / Asthenia 19/51 (37.3%) 29/50 (58%)
    Mucosal inflammation 11/51 (21.6%) 1/50 (2%)
    Pyrexia 10/51 (19.6%) 5/50 (10%)
    Chills 6/51 (11.8%) 3/50 (6%)
    Oedema peripheral 3/51 (5.9%) 5/50 (10%)
    Asthenia 2/51 (3.9%) 4/50 (8%)
    Pain 2/51 (3.9%) 4/50 (8%)
    Chest pain 0/51 (0%) 3/50 (6%)
    Infections and infestations
    Upper respiratory tract infection 6/51 (11.8%) 2/50 (4%)
    Pharyngitis 0/51 (0%) 3/50 (6%)
    Investigations
    Blood alkaline phosphatase increased 8/51 (15.7%) 1/50 (2%)
    Aspartate aminotransferase increased 7/51 (13.7%) 0/50 (0%)
    White blood cell count decreased 7/51 (13.7%) 2/50 (4%)
    Haemoglobin decreased 6/51 (11.8%) 4/50 (8%)
    Alanine aminotransferase increased 5/51 (9.8%) 0/50 (0%)
    Neutrophil count decreased 5/51 (9.8%) 0/50 (0%)
    Weight decreased 5/51 (9.8%) 0/50 (0%)
    Platelet count decreased 2/51 (3.9%) 3/50 (6%)
    Metabolism and nutrition disorders
    Decreased appetite 17/51 (33.3%) 13/50 (26%)
    Dehydration 6/51 (11.8%) 6/50 (12%)
    Hyperglycaemia 6/51 (11.8%) 1/50 (2%)
    Hypokalaemia 5/51 (9.8%) 3/50 (6%)
    Hypocalcaemia 4/51 (7.8%) 4/50 (8%)
    Musculoskeletal and connective tissue disorders
    Myalgia / Arthralgia 14/51 (27.5%) 22/50 (44%)
    Arthralgia 12/51 (23.5%) 17/50 (34%)
    Back pain 7/51 (13.7%) 5/50 (10%)
    Pain in extremity 5/51 (9.8%) 7/50 (14%)
    Muscle spasms 4/51 (7.8%) 2/50 (4%)
    Bone pain 3/51 (5.9%) 5/50 (10%)
    Musculoskeletal pain 3/51 (5.9%) 4/50 (8%)
    Musculoskeletal chest pain 2/51 (3.9%) 4/50 (8%)
    Myalgia 2/51 (3.9%) 11/50 (22%)
    Nervous system disorders
    Peripheral Neuropathy 18/51 (35.3%) 23/50 (46%)
    Neuropathy peripheral 16/51 (31.4%) 15/50 (30%)
    Headache 7/51 (13.7%) 6/50 (12%)
    Dizziness 6/51 (11.8%) 4/50 (8%)
    Dysgeusia 4/51 (7.8%) 3/50 (6%)
    Paraesthesia 4/51 (7.8%) 2/50 (4%)
    Peripheral sensory neuropathy 4/51 (7.8%) 8/50 (16%)
    Peripheral motor neuropathy 0/51 (0%) 3/50 (6%)
    Psychiatric disorders
    Depression 4/51 (7.8%) 2/50 (4%)
    Insomnia 4/51 (7.8%) 1/50 (2%)
    Anxiety 3/51 (5.9%) 3/50 (6%)
    Respiratory, thoracic and mediastinal disorders
    Cough 10/51 (19.6%) 6/50 (12%)
    Dyspnoea 6/51 (11.8%) 13/50 (26%)
    Oropharyngeal pain 6/51 (11.8%) 3/50 (6%)
    Dysphonia 3/51 (5.9%) 0/50 (0%)
    Epistaxis 1/51 (2%) 5/50 (10%)
    Pleural effusion 1/51 (2%) 4/50 (8%)
    Skin and subcutaneous tissue disorders
    Alopecia 20/51 (39.2%) 21/50 (42%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Results Point of Contact

    Name/Title Eisai Medical Information
    Organization Eisai Inc.
    Phone 888-274-2378 ext +1
    Email esi_oncmedinfo@eisai.com
    Responsible Party:
    Eisai Inc.
    ClinicalTrials.gov Identifier:
    NCT00879086
    Other Study ID Numbers:
    • E7389-G000-209
    First Posted:
    Apr 9, 2009
    Last Update Posted:
    Dec 1, 2021
    Last Verified:
    Oct 1, 2021