A Study Comparing Eribulin Mesylate and Ixabepilone in Causing or Exacerbating Neuropathy in Participants With Advanced Breast Cancer
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
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:
|
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
- 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
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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
Inclusion criteria:
- 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:
-
Subjects who have received prior ixabepilone therapy.
-
Subjects with prior participation in an eribulin clinical study, even if not assigned to eribulin treatment.
-
Subjects with pre-existing neuropathy Grade greater than or equal to 2.
-
Subjects with a history of diabetes mellitus Type 1 or 2.
-
Subjects with bilateral mastectomy which included bilateral axillary lymph node dissection.
-
Subjects with missing digits required for vibration assessment.
-
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.- E7389-G000-209
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
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) |
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) |
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)
|
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%
|
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%
|
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%
|
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%
|
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
|
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%
|
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
|
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
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 |
esi_oncmedinfo@eisai.com |
- E7389-G000-209