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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01269346
• Other study ID #: E7389-A001-208
• Status: Completed
• Phase: Phase 2
• Start date: December 2010
• Est. completion date: May 2016

Study information

• Verified date: February 2017
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: May 2016
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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.

Locations

Country	Name	City	State
United States	Peachtree Hematology Oncology Associates, PC	Atlanta	Georgia
United States	Texas Oncology - Beaumont Marnie McFaddin Ward Cancer Center	Beaumont	Texas
United States	Cancer Care of the Cascades	Bend	Oregon
United States	Charleston Hematology/Oncology	Charleston	South Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Texas Oncology - Medical City Dallas	Dallas	Texas
United States	Florida Cancer Care	Davie	Florida
United States	University of Colorado	Denver	Colorado
United States	Texas Oncology - El Paso Cancer Treatment Center Grandview	El Paso	Texas
United States	C. Michael Jones, MD	Germantown	Tennessee
United States	Texas Oncology - Memorial City	Houston	Texas
United States	Jackson Oncology Associates, PLLC	Jackson	Mississippi
United States	Florida Oncology Associates	Jacksonville	Florida
United States	Columbia Basin Hematology and Oncology	Kennewick	Washington
United States	Medical Oncology Associates of Wyoming Valley, P.C.	Kingston	Pennsylvania
United States	Northwest Georgia Oncology Centers, P.C.	Marietta	Georgia
United States	Texas Oncology - McAllen South Second Street	McAllen	Texas
United States	Montgomery Cancer Center	Mount Sterling	Kentucky
United States	Weill Cornell Breast Clinic	New York	New York
United States	Pensisula Cancer Institute	Newport News	Virginia
United States	Ocala Oncology Center	Ocala	Florida
United States	Raleigh Hematology Associates	Raleigh	North Carolina
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Cancer Care Centers of South Texas	San Antonio	Texas
United States	Texas Oncology - Sherman	Sherman	Texas
United States	Texas Oncology - Sugar Land	Sugar Land	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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