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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT01268150
First received: December 28, 2010
Last updated: June 28, 2016
Last verified: June 2016
  Purpose
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.

Condition Intervention Phase
Locally Recurrent
Metastatic Breast Cancer ( HER2 Negative)
Drug: Eribulin mesylate
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Objective Response Rate (ORR) [ 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 ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Time to First Response (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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • To Assess the Incidence of Adverse Events (AEs) of Eribulin Mesylate [ 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 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 56
Study Start Date: February 2011
Study Completion Date: August 2013
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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).
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01268150

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT01268150     History of Changes
Other Study ID Numbers: E7389-A001-206 
Study First Received: December 28, 2010
Results First Received: May 11, 2016
Last Updated: June 28, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Mitogens
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 22, 2016