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

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Eribulin mesylate

About this trial

This is an interventional treatment trial for Locally Recurrent

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Experimental

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.

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.

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.

Full Information

NCT ID

NCT01268150

First Posted

December 28, 2010

Last Updated

June 16, 2023

Sponsor

Eisai Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01268150

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2016

Overall Recruitment Status

Completed

Study Start Date

February 2011 (undefined)

Primary Completion Date

March 2012 (Actual)

Study Completion Date

August 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eisai Inc.

4. Oversight

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Locally Recurrent, Metastatic Breast Cancer ( HER2 Negative)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

56 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Experimental

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Eribulin mesylate

Intervention Description

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.

Primary Outcome Measure Information:

Title

Objective Response Rate (ORR)

Description

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

Secondary Outcome Measure Information:

Title

Time to First Response (CR or PR)

Description

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

Title

Duration of Response

Description

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

Title

Progression-Free Survival (PFS)

Description

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

Other Pre-specified Outcome Measures:

Title

To Assess the Incidence of Adverse Events (AEs) of Eribulin Mesylate

Description

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

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sam Misir

Organizational Affiliation

Eisai Inc.

Official's Role

Study Director

Facility Information:

Facility Name

University of Miami

City

Miami

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

Facility Name

Augusta Oncology Associates

City

Augusta

State/Province

Georgia

ZIP/Postal Code

30901

Country

United States

Facility Name

Central Georgia Cancer Care

City

Macon

State/Province

Georgia

ZIP/Postal Code

31088

Country

United States

Facility Name

Northwest Georgia Oncology Centers, P.C.

City

Marietta

State/Province

Georgia

ZIP/Postal Code

30060

Country

United States

Facility Name

Central Indiana Cancer Centers

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46219

Country

United States

Facility Name

Missouri Cancer Associates

City

Columbia

State/Province

Missouri

ZIP/Postal Code

65201

Country

United States

Facility Name

Hematology Oncology Centers of Northern Rockies

City

Billings

State/Province

Montana

ZIP/Postal Code

59101

Country

United States

Facility Name

New York Oncology Hematology, P.C.

City

Albany

State/Province

New York

ZIP/Postal Code

12206

Country

United States

Facility Name

Weill Cornell Medical Center

City

New York

State/Province

New York

ZIP/Postal Code

10021

Country

United States

Facility Name

Northwest Cancer Specialists, P.C.

City

Portland

State/Province

Oregon

ZIP/Postal Code

97225

Country

United States

Facility Name

The West Clinic

City

Memphis

State/Province

Tennessee

ZIP/Postal Code

38120

Country

United States

Facility Name

Texas Oncology- Bedford

City

Bedford

State/Province

Texas

ZIP/Postal Code

76022

Country

United States

Facility Name

Texas Oncology - Medical City Dallas

City

Dallas

State/Province

Texas

ZIP/Postal Code

75230-2510

Country

United States

Facility Name

Texas Oncology-Dallas Presbyterian Hospital

City

Dallas

State/Province

Texas

ZIP/Postal Code

75231

Country

United States

Facility Name

Cancer Care Centers of South Texas

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78217

Country

United States

Facility Name

Texas Oncology- Tyler

City

Tyler

State/Province

Texas

ZIP/Postal Code

75702

Country

United States

Facility Name

Columbia Basin Hematology and Oncology

City

Kennewick

State/Province

Washington

ZIP/Postal Code

99336

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

24699910

Citation

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.

Results Reference

derived

Locally Recurrent, Metastatic Breast Cancer ( HER2 Negative)

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial