A Study of Single-Agent Eribulin Mesylate as First-Line Therapy for Locally Recurrent or Metastatic Human Epidermal Growth Factor Receptor Two (HER2) Negative Breast Cancer

Study Overview
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Brief Summary
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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
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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).

Official Title
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A Phase 2, Multicenter, Single-Arm Study of Single-Agent Eribulin Mesylate as First-Line Therapy for Locally Recurrent or Metastatic Human Epidermal Growth Factor Receptor Two (HER2) Negative Breast Cancer

Conditions
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Locally Recurrent, Metastatic Breast Cancer ( HER2 Negative)

Intervention / Treatment
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* Drug: Eribulin mesylate


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br> | Drug: Eribulin mesylate<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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 | 
| 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. | 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 | 
| 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. | 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 |