Locally Recurrent, Metastatic Breast Cancer ( HER2 Negative)
Conditions
Brief summary
The purpose of this study is to assess the efficacy and safety of single-agent eribulin mesylate for first-line treatment of subjects with locally recurrent or metastatic breast cancer.
Detailed description
This is a multicenter, single-arm, Phase 2 trial to assess the efficacy and safety of single-agent eribulin mesylate for first-line treatment of subjects with locally recurrent or metastatic human epidermal growth factor receptor (HER2)-negative breast cancer. A total of 52 adult female subjects will be enrolled and treated with eribulin mesylate (1.4 mg/m2 as an intravenous \[i.v.\] infusion over 2 to 5 minutes on Days 1 and 8 of each 3-week cycle).
Interventions
DRUGEribulin mesylate
Eribulin mesylate 1.4 mg/m2 will be administered as an intravenous (IV) infusion (over 2 to 5 minutes) on Days 1 and 8 of each 3-week cycle.
Sponsors
Eisai Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria Females age 18 years or older at the time of informed consent Have histologically or cytologically proven adenocarcinoma of the breast Subjects with locally recurrent or metastatic disease with at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria v 1.1 Human epidermal growth factor receptor (HER2)-negative disease as determined by fluorescence in situ hybridization (FISH) or 0 or 1+ by immunohistochemical (IHC) staining. Life expectancy of greater than 24 weeks Eastern Cooperative Oncology Group (ECOG) Performance Score (PS) of 0, 1 or 2 At least 12 months since prior neoadjuvant or adjuvant chemotherapy At least 2 weeks since prior radiotherapy or endocrine therapy, with complete recovery from the effects of these interventions Adequate renal function Adequate bone marrow function Adequate liver function Key
Exclusion criteria
Subjects who meet any of the following criteria will be excluded from participation in this study: Prior chemotherapy, biologic therapy, or investigational therapy for locally recurrent or metastatic breast cancer Subjects who have had a prior malignancy other than carcinoma in situ of the cervix or nonmelanoma skin cancer Prior exposure of greater than 360 mg/m2 doxorubicin or liposomal doxorubicin, greater than 120 mg/m2 mitoxantrone, greater than 90 mg/m2 idarubicin, or greater than720 mg/m2 epirubicin Inflammatory breast cancer Clinically significant cardiovascular impairment Subjects with known CNS disease are not eligible, except for those with treated brain metastasis. Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring the use of oxygen Currently pregnant or breast-feeding. Subjects with pre-existing Grade 3 or 4 neuropathy. Any peripheral neuropathy must recover to Grade 2 before enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Cycle 1 (Day 1) until first evidence of disease progression, assessed up to the data cutoff date (30 Aug 2013) up to 2.5 years | The ORR was defined as the percentage of participants with best overall response (BOR) of confirmed complete response (CR) or partial response (PR), based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Targeted lesions were assessed by computed tomography (CT) and magnetic resonance imaging (MRI) which were then assessed by the investigator based on RECIST. CR was defined as the disappearance of all target lesions. PR was defined as at least 30% decrease in the sum of diameters of target lesions, taking as reference baseline sum diameters. Possible CR and PR had to be confirmed no fewer than 4 weeks after the initial response assessment. A brain and bone scan was performed by CT/MRI within 1 week after confirmation of a response to ensure no new metastases. To be assigned a status of CR or PR, changes in tumor measurements had to be confirmed by repeat evaluations, to be performed not fewer than 4 weeks after the response criteria were first met. ORR = CR + PR |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Response (CR or PR) | Treatment Phase (Day 1 Cycle 1) to earliest date of confirmed objective response (CR or PR), assessed up to the data cutoff date (30 Aug 2013) up to 2.5 years | Time to first response was defined for participants whose BOR was a CR or PR. Analysis was based on the Kaplan-Meier estimated number of months to CR or PR. This statistical analysis method measures the effect of study drug on CR or PR. |
| Duration of Response | First date of CR or PR to PD or Death from any cause, assessed up to the data cutoff date (30 Aug 2013) up to 2.5 years | Duration of response was measured for participants who were responders only, had attained a BOR that was CR or PR. The duration of response was measured from time that response criteria for CR or PR (whichever was recorded first) were first met until the date that progressive disease (PD) or death from any cause was first objectively documented. Participants who did not have PD were censored on the day of their last tumor assessment. Duration of response was summarized for the responders using Kaplan-Meier estimation method. This statistical analysis method measures the effect of study drug on the length of response time. |
| Progression-Free Survival (PFS) | Treatment Phase (Day 1 Cycle 1) to date of progressive disease or death, whichever occurred first, assessed up to the data cutoff date (30 Aug 2013) up to 2.5 years | PFS was defined as the time from the date of the first dose of study drug until the date of first documentation of PD or date of death from any cause, whichever occurred first. Participants who died without reported PD were considered to have progressed on the day of their death. Participants who were lost to follow-up or alive and without reported PD at the end of study were censored on the date of their last tumor assessment. Participants without evidence of PD upon discontinuation of study drug during the Extension Phase returned to the clinic for disease evaluation and PFS calculation every 12 weeks until PD was documented. PFS was analyzed using Kaplan-Meier product-limit estimates. This statistical analysis method measures the effect of study drug on PFS. |
Other
| Measure | Time frame | Description |
|---|---|---|
| To Assess the Incidence of Adverse Events (AEs) of Eribulin Mesylate | Baseline until End of Treatment (within 21 days of last dose), assessed up to the data cutoff date (30 Aug 2013) up to 2.5 years | Treatment-emergent adverse events (TEAEs) were defined as AEs that emerged during treatment, having been absent at pretreatment, and occurring within 30 days of the last dose of study treatment, or if they were present prior to the first dose administration and increased in severity during the study. For each AE a participant with two or more TEAEs in that category were counted only once. TEAEs were considered related if the relationship of the event to study drug was possibly or probably related. Serious adverse events (SAEs) were defined as any untoward medical experience that resulted in death, was life-threatening, required hospitalization or prolongation of hospitalization, persistent or significant disability/incapacity, or was a congenital anomaly/birth defect. Safety information will be summarized with adverse events. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Eribulin Mesylate Eribulin mesylate at 1.4 mg/m\^2 was administered as an intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 of each 3-week cycle. | 56 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Extension Phase | Adverse Event | 3 |
| Extension Phase | Disease progression | 18 |
| Extension Phase | Other | 6 |
| Treatment Phase | Adverse Event | 3 |
| Treatment Phase | Other | 4 |
| Treatment Phase | Progression of disease | 18 |
| Treatment Phase | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Eribulin Mesylate |
|---|---|
| Age, Continuous | 57.0 Years STANDARD_DEVIATION 10.78 |
| Sex: Female, Male Female | 56 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 56 / 56 |
| serious Total, serious adverse events | 17 / 56 |
Outcome results
Primary
Objective Response Rate (ORR)
The ORR was defined as the percentage of participants with best overall response (BOR) of confirmed complete response (CR) or partial response (PR), based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Targeted lesions were assessed by computed tomography (CT) and magnetic resonance imaging (MRI) which were then assessed by the investigator based on RECIST. CR was defined as the disappearance of all target lesions. PR was defined as at least 30% decrease in the sum of diameters of target lesions, taking as reference baseline sum diameters. Possible CR and PR had to be confirmed no fewer than 4 weeks after the initial response assessment. A brain and bone scan was performed by CT/MRI within 1 week after confirmation of a response to ensure no new metastases. To be assigned a status of CR or PR, changes in tumor measurements had to be confirmed by repeat evaluations, to be performed not fewer than 4 weeks after the response criteria were first met. ORR = CR + PR
Time frame: Cycle 1 (Day 1) until first evidence of disease progression, assessed up to the data cutoff date (30 Aug 2013) up to 2.5 years
Population: Full analysis set included all participants who received at least one dose of eribulin mesylate.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eribulin Mesylate | Objective Response Rate (ORR) | 28.6 Percentage of participants |
Secondary
Duration of Response
Duration of response was measured for participants who were responders only, had attained a BOR that was CR or PR. The duration of response was measured from time that response criteria for CR or PR (whichever was recorded first) were first met until the date that progressive disease (PD) or death from any cause was first objectively documented. Participants who did not have PD were censored on the day of their last tumor assessment. Duration of response was summarized for the responders using Kaplan-Meier estimation method. This statistical analysis method measures the effect of study drug on the length of response time.
Time frame: First date of CR or PR to PD or Death from any cause, assessed up to the data cutoff date (30 Aug 2013) up to 2.5 years
Population: Full analysis set included all participants who received at least one dose of eribulin mesylate and were determined to be responders (CR or PR) to study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Eribulin Mesylate | Duration of Response | 5.8 Months |
Secondary
Progression-Free Survival (PFS)
PFS was defined as the time from the date of the first dose of study drug until the date of first documentation of PD or date of death from any cause, whichever occurred first. Participants who died without reported PD were considered to have progressed on the day of their death. Participants who were lost to follow-up or alive and without reported PD at the end of study were censored on the date of their last tumor assessment. Participants without evidence of PD upon discontinuation of study drug during the Extension Phase returned to the clinic for disease evaluation and PFS calculation every 12 weeks until PD was documented. PFS was analyzed using Kaplan-Meier product-limit estimates. This statistical analysis method measures the effect of study drug on PFS.
Time frame: Treatment Phase (Day 1 Cycle 1) to date of progressive disease or death, whichever occurred first, assessed up to the data cutoff date (30 Aug 2013) up to 2.5 years
Population: Full analysis set included all participants who received at least one dose of eribulin mesylate.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Eribulin Mesylate | Progression-Free Survival (PFS) | 6.8 Months |
Secondary
Time to First Response (CR or PR)
Time to first response was defined for participants whose BOR was a CR or PR. Analysis was based on the Kaplan-Meier estimated number of months to CR or PR. This statistical analysis method measures the effect of study drug on CR or PR.
Time frame: Treatment Phase (Day 1 Cycle 1) to earliest date of confirmed objective response (CR or PR), assessed up to the data cutoff date (30 Aug 2013) up to 2.5 years
Population: Full analysis set included all participants who received at least one dose of eribulin mesylate and were determined to be responders (CR or PR) to study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Eribulin Mesylate | Time to First Response (CR or PR) | 1.4 Months |
Other Pre-specified
To Assess the Incidence of Adverse Events (AEs) of Eribulin Mesylate
Treatment-emergent adverse events (TEAEs) were defined as AEs that emerged during treatment, having been absent at pretreatment, and occurring within 30 days of the last dose of study treatment, or if they were present prior to the first dose administration and increased in severity during the study. For each AE a participant with two or more TEAEs in that category were counted only once. TEAEs were considered related if the relationship of the event to study drug was possibly or probably related. Serious adverse events (SAEs) were defined as any untoward medical experience that resulted in death, was life-threatening, required hospitalization or prolongation of hospitalization, persistent or significant disability/incapacity, or was a congenital anomaly/birth defect. Safety information will be summarized with adverse events. AEs were graded on a five-point scale according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Time frame: Baseline until End of Treatment (within 21 days of last dose), assessed up to the data cutoff date (30 Aug 2013) up to 2.5 years
Population: Safety Analysis Set population included all participants who received at least one dose of study drug and had at least one postbaseline safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eribulin Mesylate | To Assess the Incidence of Adverse Events (AEs) of Eribulin Mesylate | TEAEs | 100.0 Percentage of participants |
| Eribulin Mesylate | To Assess the Incidence of Adverse Events (AEs) of Eribulin Mesylate | Treatment-related TEAEs | 100.0 Percentage of participants |
| Eribulin Mesylate | To Assess the Incidence of Adverse Events (AEs) of Eribulin Mesylate | Serious TEAEs | 30.4 Percentage of participants |
| Eribulin Mesylate | To Assess the Incidence of Adverse Events (AEs) of Eribulin Mesylate | Treatment-related Serious TEAEs | 8.9 Percentage of participants |
| Eribulin Mesylate | To Assess the Incidence of Adverse Events (AEs) of Eribulin Mesylate | TEAEs leading to withdrawl of study drug | 10.7 Percentage of participants |
| Eribulin Mesylate | To Assess the Incidence of Adverse Events (AEs) of Eribulin Mesylate | TEAEs leading to dose reduction | 35.7 Percentage of participants |