Eribulin With Trastuzumab as First-line Therapy for Locally Recurrent or Metastatic HER2 Positive Breast Cancer

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Eribulin Mesylate

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80204
      • University of Colorado
  • Florida
    • Davie, Florida, United States, 33328
      • Florida Cancer Care
    • Jacksonville, Florida, United States, 32256
      • Florida Oncology Associates
    • Ocala, Florida, United States, 34471
      • Ocala Oncology Center
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Peachtree Hematology Oncology Associates, PC
    • Marietta, Georgia, United States, 30060
      • Northwest Georgia Oncology Centers, P.C.
  • Kentucky
    • Mount Sterling, Kentucky, United States, 40353
      • Montgomery Cancer Center
  • Mississippi
    • Jackson, Mississippi, United States, 39202
      • Jackson Oncology Associates, PLLC
  • Missouri
    • Saint Joseph, Missouri, United States, 64507
      • Heartland Regional Medical Center
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Breast Clinic
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • Raleigh Hematology Associates
  • Oregon
    • Bend, Oregon, United States, 97701
      • Cancer Care of the Cascades
  • Pennsylvania
    • Kingston, Pennsylvania, United States, 18704
      • Medical Oncology Associates of Wyoming Valley, P.C.
  • South Carolina
    • Charleston, South Carolina, United States, 29403
      • Medical University of South Carolina
    • Charleston, South Carolina, United States, 29403
      • Charleston Hematology/Oncology
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • C. Michael Jones, MD
  • Texas
    • Beaumont, Texas, United States, 77702-1449
      • Texas Oncology - Beaumont Marnie McFaddin Ward Cancer Center
    • Dallas, Texas, United States, 75201
      • Texas Oncology - Medical City Dallas
    • El Paso, Texas, United States, 79902
      • Texas Oncology - El Paso Cancer Treatment Center Grandview
    • Houston, Texas, United States, 77024
      • Texas Oncology - Memorial City
    • McAllen, Texas, United States, 78503
      • Texas Oncology - McAllen South Second Street
    • San Antonio, Texas, United States, 78217
      • Cancer Care Centers of South Texas
    • Sherman, Texas, United States, 75090
      • Texas Oncology - Sherman
    • Sugar Land, Texas, United States, 77479
      • Texas Oncology - Sugar Land
  • Virginia
    • Newport News, Virginia, United States, 23601
      • Pensisula Cancer Institute
  • 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:

• 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

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: 1	Drug: Eribulin 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Response	Time to first response was defined for participants whose best overall response was a CR or PR.	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
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.	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
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.	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
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.	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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: December 31, 2010
• First Submitted That Met QC Criteria: January 3, 2011
• First Posted (Estimated): January 4, 2011

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 16, 2023
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Locally recurrent; metastatic HER2Positive breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: E7389-A001-208