Eribulin Versus Vinorelbine in Subjects With Locally Recurrent or Metastatic Breast Cancer Previously Treated With Anthracyclines and Taxanes

NCT02225470 | Completed Phase 3

• 1 other identifier: E7389-C086-304
• Study Type: interventional
• Target: 530
• Locations: 1 country
• Sites: 35

Brief Summary

This study is designed as an open-label randomized parallel two-arm multicenter efficacy, pharmacokinetics and safety study of intravenously administered eribulin versus intravenously administered vinorelbine in Chinese population. Eligible female subjects will have measurable disease according to RECIST 1.1 with the modification that chest x-ray cannot be used for assessment of disease.

Conditions

HER2-Negative Breast Cancer; Triple Negative Breast Cancer; Breast Cancer; Cancer of Breast; Breast Tumors

Keywords

Locally Recurrent or Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (9)

• Progression-Free Survival (PFS) of Eribulin Arm by tumor assessment : Time to disease progression

  Baseline until date of recorded disease progression or death, or up to 2 years

• Progression-Free Survival (PFS) of Vinorelbine Arm by tumor assessment: Time to disease progression

  Baseline until date of recorded disease progression or death, or up to 2 years

• Maximum observed plasma concentration (Cmax) of Eribulin Arm in a minimum of 15 subjects

  Day 1 and Day 8

• Time at which the highest drug concentration occurs (tmax) of Eribulin Arm in a minimum of 15 subjects

  Day 1 and Day 8

• Area under the plasma concentration-time curve (AUC) of Eribulin Arm in a minimum of 15 subjects

  Day 1 and Day 8

• Terminal phase rate constant (lambda Z) of Eribulin Arm in a minimum of 15 subjects

  Day 1 and Day 8

• Terminal elimination phase half-life (t1/2) of Eribulin Arm in a minimum of 15 subjects

  Day 1 and Day 8

• Distribution volume at steady-state (Vss) of Eribulin Arm in a minimum of 15 subjects

  Day 1 and Day 8

• Total clearance (CL) of Eribulin Arm in a minimum of 15 subjects

  Day 1 and Day 8

Secondary Outcomes (7)

• Overall Survival (OS)

  Baseline until date of death, or up 5 years

• Duration of Response

  Baseline until date of recorded disease progression or death or up to 5 years

• Objective Response Rate (ORR)

  Baseline until date of recorded disease progression or death, or up to 5 years

• Evaluate safety parameters such as electrocardiograms

  Baseline until date of recorded disease progression or death

• Evaluate safety assessments parameters such as vital signs( VS)

  Baseline until date of recorded disease progression or death

Study Arms (2)

Arm A, E7389 (Eribulin Mesylate)

EXPERIMENTAL

The eribulin mesylate dose will be 1.4 mg/m2 administered as an intravenous bolus over 2 to 5 minutes on Days 1 and 8 of each 21-day cycle.

Drug: E7389 (Eribulin Mesylate)

Arm B, Vinorelbine injection

ACTIVE COMPARATOR

The vinorelbine dose will be 25 mg/m2 administered as an intravenous bolus on Days 1, 8, and 15 of each 21-day treatment cycle.

Drug: Vinorelbine injection

Interventions

E7389 (Eribulin Mesylate) DRUG

Arm A, E7389 (Eribulin Mesylate)

Vinorelbine injection DRUG

Arm B, Vinorelbine injection

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must meet all of the following criteria to be included in this study.
• Female subjects with histologically or cytologically confirmed carcinoma of the breast:
• Subjects with locally recurrent or metastatic disease who have received at least two, and a maximum of five, prior chemotherapeutic regimens for breast cancer, at least two of which were administered for treatment of locally recurrent or metastatic disease. Prior therapy must be documented by the following criteria prior to entry onto study:
• Regimens must have included an anthracycline (e.g., doxorubicin, epirubicin), and a taxane (e.g., paclitaxel, docetaxel) in any combination or order. Prior treatment with any of these agents is not required if the agents are contraindicated for a prospective subject and documented in her medical history.
• Some of these regimens may have been administered as adjuvant and/or neoadjuvant therapy, but at least two must have been given for locally recurrent or metastatic disease.
• Subjects must have proven refractory to the most recent chemotherapy as documented by progression on or within 6 months of their last chemotherapy.
• Subjects with Her2/neu positive tumors may also have been treated with any Her2/neu targeted agents including antibodies, small compounds or investigational drugs.
• Subjects may also have been treated with antihormonal therapy.
• Have measurable disease meeting the following criteria:
• At least one lesion of greater than or equal to 1.0 cm in the longest diameter for a non-lymph node, or greater than or equal to 1.5 cm in the short-axis diameter for a lymph node which is serially measurable according to RECIST 1.1 using computerized tomography/magnetic resonance imaging (CT/MRI). If there is only one target lesion and it is a non-lymph node, it should have a longest diameter of greater than or equal to 1.5 cm.
• Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies such as radiofrequency (RF) ablation must show evidence of progressive disease based upon RECIST 1.1 to be used as a target lesion.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2.
• Life expectancy of greater than or equal to 3 months.
• subjects greater than or equal to 18 years old Age and less than or equal to 70 years old at the time of informed consent.
• Adequate renal function as evidenced by serum creatinine less than or equal to 2.0 mg/dL or calculated creatinine clearance greater than or equal to 40 mL/min per the Cockcroft and Gault formula.

You may not qualify if:

• Subjects who meet any of the following criteria will be excluded from this study:
• Subjects who have received any of the following treatments within the specified period before treatment start:
• Vinorelbine has been administrated as neoadjuvant or adjuvant therapy within one year.
• Chemotherapy, radiation, Her2/neu targeted agents including trastuzumab or hormonal therapy within three weeks.
• Any investigational drug within four weeks.
• Blood transfusion, blood preparations and hematopoietic factor preparations such as G-CSF within two weeks.
• Subjects of advanced breast cancer with vinorelbine effective therapy to CR/PR/SD, and PD occurred after vinorelbine discontinuing within 6 months.
• Subjects with ineffective prior vinorelbine treatment.
• Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen.
• Subjects with brain or subdural metastases are not eligible, unless they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least four weeks before starting treatment in this study. Any signs (e.g., radiologic) and/or symptoms of brain metastases must be stable for at least four weeks before starting study treatment; and radiographic stability should be determined by comparing a contrast-enhanced CT or MRI brain scan performed during screening to a prior scan performed at least four weeks earlier.
• Subjects with meningeal carcinomatosis.
• Woman must not be pregnant as documented by a negative beta-human chorionic gonadotropin (beta-hCG) test with a minimum sensitivity 25 IU/L, or equivalent unit of beta-hCG, at Screening and Baseline; nor breastfeeding.
• Severe/uncontrolled intercurrent illness/infection.
• Significant cardiovascular impairment (history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina or myocardial infarction within the past six months, or serious cardiac arrhythmia).
• Subjects with organ allografts requiring immunosuppression therapy.

Sponsors & Collaborators

• Eisai Co., Ltd.: lead

Study Sites (35)

04 Eisai Trial Site

Bengbu, Anhui, China

Location

37 Eisai Trial Site

Hefei, Anhui, China

Location

01 Eisai Trial Site

Beijing, Beijing Municipality, China

Location

03 Eisai Trial Site

Beijing, Beijing Municipality, China

Location

33 Eisai Trial Site

Beijing, Beijing Municipality, China

Location

35 Eisai Trial Site

Beijing, Beijing Municipality, China

Location

07 Eisai Trial Site

Fuzhou, Fujian, China

Location

08 Eisai Trial Site

Fuzhou, Fujian, China

Location

20 Eisai Trial Site

Guangzhou, Guangdong, China

Location

36 Eisai Trial Site

Guangzhou, Guangdong, China

Location

10 Eisai Trial Site

Nanning, Guangxi, China

Location

12 Eisai Trial Site

Shijiazhuang, Hebei, China

Location

11 Eisai Trial Site

Harbin, Heilongjiang, China

Location

38 Eisai Trial Site

Zhengzhou, Henan, China

Location

14 Eisai Trial Site

Wuhan, Hubei, China

Location

15 Eisai Trial Site

Wuhan, Hubei, China

Location

05 Eisai Trial Site

Changsha, Hunan, China

Location

13 Eisai Trial Site

Changsha, Hunan, China

Location

34 Eisai Trial Site

Changsha, Hunan, China

Location

18 Eisai Trial Site

Nanjing, Jiangsu, China

Location

31 Eisai Trial Site

Nanjing, Jiangsu, China

Location

16 Eisai Trial Site

Changchun, Jilin, China

Location

17 Eisai Trial Site

Changchun, Jilin, China

Location

06 Eisai Trial Site

Dalian, Liaoning, China

Location

19 Eisai Trial Site

Shenyang, Liaoning, China

Location

21 Eisai Trial Site

Yinchuang, Ningxia, China

Location

24 Eisai Trial Site

Xi'an, Shaanxi, China

Location

28 Eisai Trial Site

Xi'an, Shaanxi, China

Location

22 Eisai Trial Site

Qingdao, Shandong, China

Location

09 Eisai Trial Site

Shanghai, Shanghai Municipality, China

Location

23 Eisai Trial Site

Taiyuan, Shanxi, China

Location

26 Eisai Trial Site

Chengtu, Sichuan, China

Location

27 Eisai Trial Site

Tianjin, Tianjin Municipality, China

Location

30 Eisai Trial Site

Yunnan, Yunnan, China

Location

40 Eisai Trial Site

Hangzhou, Zhejiang, China

Location

Related Publications (1)

• Yuan P, Hu X, Sun T, Li W, Zhang Q, Cui S, Cheng Y, Ouyang Q, Wang X, Chen Z, Hiraiwa M, Saito K, Funasaka S, Xu B. Eribulin mesilate versus vinorelbine in women with locally recurrent or metastatic breast cancer: A randomised clinical trial. Eur J Cancer. 2019 May;112:57-65. doi: 10.1016/j.ejca.2019.02.002. Epub 2019 Mar 29.

  PMID: 30928806 DERIVED

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

eribulin; Vinorelbine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2014
• First Posted: August 26, 2014
• Study Start: September 26, 2013
• Primary Completion: September 29, 2017
• Study Completion: June 22, 2018
• Last Updated: August 28, 2018

Record last verified: 2017-12

Locations

CN (35)