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

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

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.

Study Overview

• Status: Completed
• Conditions: Locally Recurrent; Metastatic Breast Cancer ( HER2 Negative)
• Intervention / Treatment: Drug: Eribulin mesylate

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).

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Georgia
    • Augusta, Georgia, United States, 30901
      • Augusta Oncology Associates
    • Macon, Georgia, United States, 31088
      • Central Georgia Cancer Care
    • Marietta, Georgia, United States, 30060
      • Northwest Georgia Oncology Centers, P.C.
  • Indiana
    • Indianapolis, Indiana, United States, 46219
      • Central Indiana Cancer Centers
  • Missouri
    • Columbia, Missouri, United States, 65201
      • Missouri Cancer Associates
  • Montana
    • Billings, Montana, United States, 59101
      • Hematology Oncology Centers of Northern Rockies
  • New York
    • Albany, New York, United States, 12206
      • New York Oncology Hematology, P.C.
    • New York, New York, United States, 10021
      • Weill Cornell Medical Center
  • Oregon
    • Portland, Oregon, United States, 97225
      • Northwest Cancer Specialists, P.C.
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • The West Clinic
  • Texas
    • Bedford, Texas, United States, 76022
      • Texas Oncology- Bedford
    • Dallas, Texas, United States, 75231
      • Texas Oncology-Dallas Presbyterian Hospital
    • Dallas, Texas, United States, 75230-2510
      • Texas Oncology - Medical City Dallas
    • San Antonio, Texas, United States, 78217
      • Cancer Care Centers of South Texas
    • Tyler, Texas, United States, 75702
      • Texas Oncology- Tyler
  • Washington
    • Kennewick, Washington, United States, 99336
      • Columbia Basin Hematology and Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental	Drug: Eribulin 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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

Collaborators and Investigators

• Sponsor: Eisai Inc.
• Investigators: Study Director: Sam Misir, Eisai Inc.

Publications and helpful links

General Publications

• McIntyre K, O'Shaughnessy J, Schwartzberg L, Gluck S, Berrak E, Song JX, Cox D, Vahdat LT. Phase 2 study of eribulin mesylate as first-line therapy for locally recurrent or metastatic human epidermal growth factor receptor 2-negative breast cancer. Breast Cancer Res Treat. 2014 Jul;146(2):321-8. doi: 10.1007/s10549-014-2923-9. Epub 2014 Apr 4. Erratum In: Breast Cancer Res Treat. 2014 Jul;146(2):329.

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: December 28, 2010
• First Submitted That Met QC Criteria: December 28, 2010
• First Posted (Estimated): December 29, 2010

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 16, 2023
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Neoplasms; Neoplasms by Site; Disease Attributes; Breast Diseases; Breast Neoplasms; Recurrence
• Other Study ID Numbers: E7389-A001-206