A Study of Eribulin Mesylate With Trastuzumab for Advanced or Recurrent Human Epidermal Growth Factor Receptor 2-Positive (HER2+) Breast Cancer

A Phase 1 Study of Eribulin Mesylate With Trastuzumab for Advanced or Recurrent Human Epidermal Growth Factor Receptor 2-Positive (HER2+) Breast Cancer

The purpose of the study is to evaluate dose limiting toxicity (DLT), investigate the tolerability and safety of eribulin mesylate with trastuzumab combination therapy, and estimate the recommended dose.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: E7389

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Chiba
    • Kashiwa-shi, Chiba, Japan
  • Saitama
    • Hidaka-shi, Saitama, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria

• Females aged greater than or equal to 20 years and less than 75 years at the time of informed consent.
• Histologically or cytologically confirmed with breast cancer
• Score 3+ by immunohistochemistry (IHC) or HER2 positive by Fluorescence in Situ Hybridization (FISH) method

• Subjects who meet any of the following criteria:

  • Evidence of recurrence during adjuvant chemotherapy with trastuzumab and taxane
  • Evidence of recurrence within 6 months after adjuvant chemotherapy with trastuzumab and taxane
  • Experienced prior chemotherapy including trastuzumab and taxane for advanced or recurrent breast cancer
• Adequate organ function
• Eastern Cooperative Oncology Group (ECOG)-Performance Status (PS) is 0 or 1
• Subjects who have submitted written informed consent for study entry

Exclusion Criteria

• Subjects with known brain metastasis accompanied by clinical symptoms or requiring active treatment
• Subjects with severe active infection requiring active treatment
• Subjects with large pleural effusions, ascites, or pericardial effusions requiring drainage.
• Hypersensitivity to trastuzumab, halicondrin B or halicondrin B chemical derivatives
• Known positive for human immunodeficiency virus (HIV) test or positive for hepatitis B surface (HBs antigen) or hepatitis C (HCV) by serum test.
• Subjects who are pregnant (positive B-hCG test) or breastfeeding
• Subjects judged to be ineligible for this study by the principal investigator or sub-investigator.

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: E7389; Eribulin mesylate (iv) will be administered on Day 1 and Day 8 of each cycle (3 weeks as 1 cycle). Trastuzumab (iv) will be administered as weekly use or tri-weekly use. Trastuzumab will be administered immediately after eribulin mesylate administration when used concomitantly.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Dose Limiting Toxicity (DLT)	For DLT evaluation, severity (grade) was classified according to common terminology criteria for adverse events version 4.0 (CTCAE v4.0). DLTs were defined as grade 4 neutropenia persisting for more than 7 days; grade 3 or above febrile neutropenia; grade 4 thrombocytopenia or grade 3 thrombocytopenia requiring blood transfusion; non-hematologic toxicity (excluding toxicity related to neutrophils, leukocytes, lymphocytes, platelets, CD4 lymphocytes, anemia, and bone marrow density) greater than or equal to grade 3 (Exceptions: Dose reduction was not required even when the following conditions were met: grade 3 nausea, vomiting, or diarrhea controllable with anti-emetic or anti-diarrheal medication and abnormal laboratory parameter not requiring treatment); and day 8 administration was delayed or skipped as a result of the subject did not meet the dosing riteria within cycle.	Up to 3 weeks
Number of Participants With Adverse Events	The number of subjects who developed 'treatment-emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.	From signing of informed consent up to 30 days after participant's last treatment dose or up to approximately 2 years

Collaborators and Investigators

• Sponsor: Eisai Co., Ltd.
• Investigators: Study Director: Tadashi Nakanishi, Eisai Co., Ltd.

Publications and helpful links

General Publications

• Mukai H, Saeki T, Shimada K, Naito Y, Matsubara N, Nakanishi T, Obaishi H, Namiki M, Sasaki Y. Phase 1 combination study of eribulin mesylate with trastuzumab for advanced or recurrent human epidermal growth factor receptor 2 positive breast cancer. Invest New Drugs. 2015 Feb;33(1):119-27. doi: 10.1007/s10637-014-0161-y. Epub 2014 Sep 23.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: September 12, 2011
• First Submitted That Met QC Criteria: September 12, 2011
• First Posted (Estimate): September 13, 2011

Study Record Updates

• Last Update Posted (Estimate): October 7, 2016
• Last Update Submitted That Met QC Criteria: August 29, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: Breast Cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: E7389-J081-107