Breast Cancer
Conditions
Keywords
Locally recurrent, metastatic HER2Positive breast cancer
Brief summary
This is a multicenter phase 2 study designed to evaluate the safety and efficacy of eribulin mesylate in combination with trastuzumab as first line treatment in female subjects with locally recurrent or metastatic human epidermal growth factor receptor (HER2) positive breast cancer.
Interventions
DRUGEribulin Mesylate
Eribulin mesylate 1.4 mg/m2 administered as an intravenous (IV) infusion (over 2 to 5 minutes) on Days 1 and 8 of each 3-week cycle. Trastuzumab 8 mg/kg will be administered as in IV infusion over a 90-minute period on Day 1 of Cycle 1. Thereafter, trastuzumab 6 mg/kg will be administered as an IV infusion over a 30-minute period on Day 1 of each subsequent 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: * Age 18 years or older * Histologically or cytologically proven adenocarcinoma of the breast * Subjects who have locally recurrent or metastatic disease with at least one measurable lesion * HER2 positive as determined by score of 3 on immunohistochemistry (IHC) staining or gene amplification by fluorescence in situ hybridization (FISH). * Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0, 1 or 2 * At least 12 months since prior neoadjuvant or adjuvant chemotherapy * At least 2 weeks since prior radiotherapy, endocrine therapy, trastuzumab, or lapatinib, with complete recovery from the effects of these interventions * Adequate renal function * Adequate bone marrow function * Adequate liver function * Adequate cardiac function Key
Exclusion criteria
* Prior chemotherapy, biologic therapy, or investigational therapy for locally recurrent or metastatic HER2 breast cancer. * Subjects who have had a prior malignancy other than carcinoma in situ of the cervix, or nonmelanoma skin cancer * Prior exposure to greater than 360 mg/m2 doxorubicin or liposomal doxorubicin, greater than 120 mg/m2 mitoxantrone, greater than 90 mg/m2 idarubicin, or greater than 720 mg/m2 epirubicin * Inflammatory breast cancer * Prior history of hypertensive crisis or hypertensive encephalopathy * Clinically significant cardiovascular impairment * Subjects with known central nervous system (CNS) disease are not eligible, except for those subjects with treated brain metastasis. * Subjects with metastatic disease limited to bone are ineligible unless there is at least one lytic lesion with identifiable soft tissue components that can be evaluated by computed tomography (CT) or magnetic resonance imaging (MRI) * Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring the use of oxygen * History of bleeding diasthesis * Currently pregnant or breast-feeding. * Subjects with preexisting Grade 3 or 4 neuropathy. Any peripheral neuropathy must recover to Grade less than or equal to 2 before enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | Baseline (within 28 days of first infusion of study drug); Treatment Phase (every 6 weeks during the first 6 cycles); Extension Phase (every 12 weeks) to PR or CR | The Objective Response Rate (Complete Response plus Partial Response, (CR + PR)) was defined as the proportion of participants who have a best overall response of confirmed CR or PR based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as assessed by the Investigator. Tumor assessment was by computed tomography (CT)/magnetic resonance imaging (MRI). To assess best response (CR, PR, stable disease (SD), progressive disease (PD), or not estimable (NE)), the Investigator selected up to five measurable target lesions (2 per organ). All other lesions were identified as nontarget lesions. Each participant's overall tumor burden at Baseline was compared with subsequent measurements of the target lesions. For participants with CR or PR, changes in tumor sizes had to be confirmed by repeat evaluations performed not fewer than four weeks after the initial response assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Response | From date of first dose of study drug to the earliest date that CR or PR was objectively documented, assessed up to data cutoff (12 Sep 2013), up to approximately 2 years 9 months | Time to first response was defined for participants whose best overall response was a CR or PR. |
| Duration of Response (DOR) | Date of a confirmed CR or PR was first documented to the date of PD or death (due to any cause and in the absence of PD), whichever occurred first, or date of data cutoff (12 Sep 2013), or up to approximately 2 years 9 months | Duration of response was defined for participants whose best overall response was CR or PR. Participants who died without reported PD were considered to have progressed on the day of their death. Participants who were alive at the end of the study without reported PD were censored on the date of their last tumor assessment. |
| Progression-Free Survival (PFS) | Date of first dose of study drug to date of PD or death (from any cause) whichever came first, or date of data cutoff (12 Sep 2013), up to approximately 2 years 9 months | 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. |
| Duration of Stable Disease (SD) | Start of study treatment to date of PD or death, whichever occurred first, or date of data cutoff (12 Sep 2013), up to approximately 2 years 9 months | Defined as the period from treatment start date to the date of PD or death, whichever occurred first. Participants who were alive without having PD as of the data cutoff date were censored as of their last tumor assessment. Calculated for participants who best response was SD. |
Countries
United States
Participant flow
Pre-assignment details
A total of 64 participants were screened for entry into the study, of these participants 12 were screen failures and 52 were enrolled into the study and received at least one dose of study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Eribulin Mesylate in Combination With Trastuzumab Eribulin Mesylate: Eribulin mesylate 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.
Trastuzumab 8 mg/kg was administered as in IV infusion over a 90-minute period on Day 1 of Cycle 1. Thereafter, trastuzumab 6 mg/kg was administered as an IV infusion over a 30-minute period on Day 1 of each subsequent 21-day cycle. | 52 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Extension Phase | Adverse Event | 6 |
| Extension Phase | Clinical progression | 1 |
| Extension Phase | Disease progression | 22 |
| Extension Phase | Physician decision or participant choice | 9 |
| Extension Phase | Started a prohibited con med | 1 |
| Extension Phase | Withdrawal by Subject | 4 |
| Treatment Phase | Adverse Event | 3 |
| Treatment Phase | Disease progression | 3 |
| Treatment Phase | Other | 2 |
| Treatment Phase | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Eribulin Mesylate in Combination With Trastuzumab |
|---|---|
| Age, Continuous | 58.7 Years STANDARD_DEVIATION 10.92 |
| Sex: Female, Male Female | 51 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 52 / 52 |
| serious Total, serious adverse events | 15 / 52 |
Outcome results
Primary
Objective Response Rate
The Objective Response Rate (Complete Response plus Partial Response, (CR + PR)) was defined as the proportion of participants who have a best overall response of confirmed CR or PR based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as assessed by the Investigator. Tumor assessment was by computed tomography (CT)/magnetic resonance imaging (MRI). To assess best response (CR, PR, stable disease (SD), progressive disease (PD), or not estimable (NE)), the Investigator selected up to five measurable target lesions (2 per organ). All other lesions were identified as nontarget lesions. Each participant's overall tumor burden at Baseline was compared with subsequent measurements of the target lesions. For participants with CR or PR, changes in tumor sizes had to be confirmed by repeat evaluations performed not fewer than four weeks after the initial response assessment.
Time frame: Baseline (within 28 days of first infusion of study drug); Treatment Phase (every 6 weeks during the first 6 cycles); Extension Phase (every 12 weeks) to PR or CR
Population: FAS included all participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eribulin Mesylate in Combination With Trastuzumab | Objective Response Rate | 71.2 Percentage of participants |
Secondary
Duration of Response (DOR)
Duration of response was defined for participants whose best overall response was CR or PR. Participants who died without reported PD were considered to have progressed on the day of their death. Participants who were alive at the end of the study without reported PD were censored on the date of their last tumor assessment.
Time frame: Date of a confirmed CR or PR was first documented to the date of PD or death (due to any cause and in the absence of PD), whichever occurred first, or date of data cutoff (12 Sep 2013), or up to approximately 2 years 9 months
Population: FAS included all participants who received at least one dose of study drug. Analyzed for responders only (n = 37).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Eribulin Mesylate in Combination With Trastuzumab | Duration of Response (DOR) | 11.1 Months |
Secondary
Duration of Stable Disease (SD)
Defined as the period from treatment start date to the date of PD or death, whichever occurred first. Participants who were alive without having PD as of the data cutoff date were censored as of their last tumor assessment. Calculated for participants who best response was SD.
Time frame: Start of study treatment to date of PD or death, whichever occurred first, or date of data cutoff (12 Sep 2013), up to approximately 2 years 9 months
Population: FAS included all participants who received at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Eribulin Mesylate in Combination With Trastuzumab | Duration of Stable Disease (SD) | 7.1 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.
Time frame: Date of first dose of study drug to date of PD or death (from any cause) whichever came first, or date of data cutoff (12 Sep 2013), up to approximately 2 years 9 months
Population: FAS included all participants who received at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Eribulin Mesylate in Combination With Trastuzumab | Progression-Free Survival (PFS) | 11.6 Months |
Secondary
Time to First Response
Time to first response was defined for participants whose best overall response was a CR or PR.
Time frame: From date of first dose of study drug to the earliest date that CR or PR was objectively documented, assessed up to data cutoff (12 Sep 2013), up to approximately 2 years 9 months
Population: FAS included all participants who received at least one dose of study drug. Analyzed for responders (CR or PR) only.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Eribulin Mesylate in Combination With Trastuzumab | Time to First Response | 1.3 Months |