Eribulin in Brain Metastases From HER2-negative Breast Cancer (ERIBRAIN)

May 5, 2020 updated by: Institut Paoli-Calmettes

A Phase II Study of Eribulin in Brain Metastases From HER2-negative Breast Cancer Pre-treated With Anthracyclines and Taxanes

To evaluate the efficacy of eribulin for treatment of HER2-negative breast cancer brain metastases (BCBM)

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

This study will explore eribulin in three specific cohorts of patients with HER2-negative metastatic breast cancer harboring BCBM, pretreated with anthracyclines and taxanes:

  • Cohort A = Newly diagnosed, untreated BCBM, not candidate to initial surgery or stereotactic radiosurgery (SRS) and with pauci-symptomatic disease not requiring immediate whole-brain radiation therapy (WBRT)
  • Cohort B = BCBM pretreated with SRS and/or surgery alone, without WBRT, and not requiring immediate WBRT
  • Cohort C = BCBM pretreated with WBRT

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Angers, France
        • Institut de Cancérologie de l'Ouest - Paul Papin
      • Avignon, France
        • Institut Sainte Catherine
      • Besançon, France
        • CHU Besançon
      • Marseille, France, 13009
        • Institut Paoli-Calmettes
      • Montpellier, France, 34298
        • Institut du Cancer de Montpellier
      • Saint-Herblain, France
        • Institut de Cancérologie de l'Ouest
      • Vandœuvre-lès-Nancy, France
        • Institut de Cancérologie de Lorraine Alexis Vautrin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. At least 18 years of age.
  2. Life expectancy of 3 months or longer.
  3. ECOG (Eastern Cooperative Oncology Group) performance status of 0, 1, or 2.
  4. HER2-negative (IHC 0/1+ or 2+ and in situ hybridization negative) metastatic breast cancer
  5. Locally advanced or metastatic breast cancer that have progressed after at least one chemotherapeutic regimen for advanced disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting unless patients were not suitable for these treatments. (no limit to the number of previous lines of therapy, no need for extracranial disease)
  6. At least 2 weeks washout period post chemotherapy, targeted or biologic therapy, or radiation therapy is required prior to study entry

  7. Patient with untreated CNS disease or previous SRS/surgery without WBRT (cohorts A and B)

    • At least 1 measurable CNS lesion ≥ 10 mm on T1-weighted gadolinium-enhanced MRI, OR
    • At least one CNS tumor measuring 5-9 mm in longest diameter, plus one or two additional CNS tumors measuring ≥ 3 mm in longest diameter, for which the sum of the longest diameters is ≥ 10 mm.

  8. Patient with progressive disease harboring brain metastases after previous WBRT (cohort C)

    • At least 1 measurable CNS lesion ≥ 10 mm on T1-weighted gadolinium-enhanced MRI, OR
    • At least one CNS tumor measuring 5-9 mm in longest diameter, plus one or two additional CNS tumors measuring ≥ 3 mm in longest diameter, for which the sum of the longest diameters is ≥ 10 mm.

  9. Adequate organ function as evidenced by:

    • Absolute neutrophil count (ANC) ≥ 1.5 x 10e9/L without granulocyte-colony-stimulating factor G-CSF (filgrastim, pegfilgrastim, or equivalent) support within 7 days
    • Hemoglobin (Hgb) ≥ 9.0 g/dL (90 g/L) without blood transfusion within 7 days
    • Platelet count ≥ 100 x 10e9/L without platelet transfusion within 7 days
    • Bilirubin ≤ 1.5 X upper limit of normal (ULN), except for patients with documented history of Gilbert's disease who may have DIRECT bilirubin ≤ 1.5 X ULN
    • Alanine aminotransferase (ALT) ≤ 2.5 X ULN, except ≤ 5 X ULN for patients with liver metastases
    • Aspartate aminotransferase (AST) ≤ 2.5 X ULN, except ≤ 5 X ULN for patients with liver metastases
    • Serum creatinine ≤ 1.5 X ULN; or calculated creatinine clearance ≥ 50 mL/min (using MDRD formula), or measured creatinine clearance ≥ 50 mL/min

Exclusion Criteria:

  1. Prior therapy with eribulin.
  2. Patients should not have had major surgery or radiotherapy (therapeutic and/or palliative) within 14 days prior to initiation of study treatment, including CNS-directed radiation therapy. (Minor procedures, such as tumor biopsy, thoracentesis, or intravenous catheter placement are allowed with no waiting period)

  3. Patients may not have the following co morbid disease or concurrent illness:

    • Known cirrhosis, defined as Child Pugh class A or higher liver disease
    • Other active malignancy, except for non-melanoma skin cancer and carcinoma in situ (of the cervix or bladder)
    • Any other severe/uncontrolled inter current illness or significant co morbid conditions that in the opinion of the investigator would impair study participation or cooperation
    • Patients with the presence of an active infection, abscess or fistula
    • Known leptomeningeal disease or CNS midline shifts.
    • Any evidence of severe or uncontrolled systemic disease such as clinically significant cardiovascular, pulmonary, hepatic, renal or metabolic disease.
    • Severe conduction abnormality including significant corrected QT interval QTc prolongation >450ms.
    • Patients with grade 3/4 peripheral neuropathy.
  4. Patient candidate to SRS and or surgical resection
  5. Major clinical symptoms requiring immediate WBRT as defined by "local tumor board"
  6. Increase in corticosteroid dose in the week prior to baseline brain MRI
  7. Patients with pacemaker or implantable cardioverter-defibrillator devices incompatible with MRI assessment.
  8. Contraindication to Gadolinium infusion.
  9. Treatment ongoing with other chemotherapy, hormonal therapy, immunotherapy, other investigational agents, or biologic agents for the treatment of cancer except bisphosphonates or denosumab.
  10. Pregnant or breast-feeding patients
  11. Women of child-bearing potential without effective contraception method.
  12. Patient unable to express their consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Eribulin
eribulin 1.4 mg/m² administered intravenously between 6 and 7 cycles.
Drug: Eribulin
Patients will receive eribulin 1.4 mg/m² administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy of eribulin for treatment of HER2-negative BCBM
Time Frame: from inclusion until 30 days after completion of treatment
By estimating central nervous system (CNS) objective response rate per RANO-BM criteria. CNS objective response rate will be defined as the rate of patients with a partial response or a complete response as defined by RANO-BM criteria (Lin et al. 2015)
from inclusion until 30 days after completion of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety of Eribulin in this population
Time Frame: from Eribulin initiation until 30 days after completion of treatment
Toxicity will be evaluated before every chemotherapy infusion according to NCI CTCAE v5.0 criteria. All treatment-related adverse events will be collected. The rate of grade 3 to 5 adverse events will be analyzed
from Eribulin initiation until 30 days after completion of treatment
Time to WBRT (cohort A and B)
Time Frame: from Eribulin initiation to the time of the first dose of whole brain radiation therapy - up to 28 months
Time to WBRT will be defined as the time from Eribulin initiation to WBRT start
from Eribulin initiation to the time of the first dose of whole brain radiation therapy - up to 28 months
CNS progression-free survival
Time Frame: from Eribulin initiation until the date of first documented CNS disease progression or date of death from any cause - up to 28 months
CNS progression-free survival will be defined as the time from Eribulin initiation to CNS disease progression according to RANO-BM criteria or death from any cause
from Eribulin initiation until the date of first documented CNS disease progression or date of death from any cause - up to 28 months
Overall survival
Time Frame: from Eribulin initiation to death
Overall survival will be defined as the time from Eribulin initiation to death from any cause
from Eribulin initiation to death
Change in cognitive function
Time Frame: From Eribulin initiation up to 7 days after study treatment discontinuation
Cognitive function will be evaluated by self-report Fact-Cog v3.0 questionnaires (French validated version;(Joly et al. 2012)) that will have to be filled every two cycles (before every day 1 infusion)
From Eribulin initiation up to 7 days after study treatment discontinuation
Quality of life measured by Functional Assessment of Cancer Therapy-Brain Metastasis
Time Frame: From Eribulin initiation up to 7 days after study treatment discontinuation
Quality of life will be measured by Functional Assessment of Cancer Therapy-Brain Metastasis (FACT-Br v4.0, (Thavarajah et al. 2014)) questionnaire. This questionnaire will be filled every two cycles
From Eribulin initiation up to 7 days after study treatment discontinuation

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival for non-CNS disease
Time Frame: from Eribulin initiation until the date of first documented extra-cranial disease progression or date of death from any cause - up to 28 months
Extracranial progression-free survival will be defined as the time from Eribulin initiation to disease progression according to RECIST 1.1 criteria (Schwartz et al. 2016) or death from any cause. Thoracic and abdominal CT-scans will be performed as recommended in each participating center (usually every 6 weeks) to assess non CNS disease (extracranial PFS, non-CNS response rate, and clinical benefit). Non-CNS disease will be evaluated according to investigator assessment.
from Eribulin initiation until the date of first documented extra-cranial disease progression or date of death from any cause - up to 28 months
Bi-compartmental progression-free survival (PFS)
Time Frame: from Eribulin initiation until the date of first documented progression or date of death from any cause - up to 28 months
Bi-compartmental PFS will be defined as the time from Eribulin initiation to CNS disease progression according to RANO-BM criteria or non-CNS disease progression according to RECIST 1.1 criteria or death from any cause
from Eribulin initiation until the date of first documented progression or date of death from any cause - up to 28 months
Overall response rate for extra-CNS disease
Time Frame: from Eribulin initiation until 30 days after completion of treatment
The overall response rate for non-CNS disease will be defined as the rate of patients with a partial response or a complete response according to RECIST 1.1 criteria
from Eribulin initiation until 30 days after completion of treatment
Clinical benefit for both CNS and extra-CNS disease
Time Frame: partial response or complete response or disease stabilization > 6 months
The clinical benefit rate will be defined as the rate of patients with a partial response or a complete response or disease stabilization > 6 months. Clinical benefit will be assessed for both CNS (using RANO-BM criteria) and non-CNS disease (using RECIST 1.1 criteria), separately
partial response or complete response or disease stabilization > 6 months
Eribulin efficacy according to hormone receptors expression
Time Frame: from Eribulin initiation until 30 days after completion of treatment
CNS objective response rates will be assessed according to hormone receptors expression (positive vs negative). A case will be defined as hormone receptors negative if both estrogen receptor and progesterone receptor expression are expressed by less than 10% of tumor cells
from Eribulin initiation until 30 days after completion of treatment
Efficacy comparison between patients with and without non-CNS disease
Time Frame: from Eribulin initiation until 30 days after completion of treatment
CNS objective response rates will be assessed according the presence of non-CNS disease ('CNS only' vs 'not CNS only').
from Eribulin initiation until 30 days after completion of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut Paoli-Calmettes

Collaborators

Eisai Inc.

Investigators

  • Principal Investigator: Renaud SABATIER, MD, Institut Paoli-Calmettes

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 26, 2019

Primary Completion (Actual)

April 14, 2020

Study Completion (Actual)

April 14, 2020

Study Registration Dates

First Submitted

August 6, 2018

First Submitted That Met QC Criteria

August 16, 2018

First Posted (Actual)

August 20, 2018

Study Record Updates

Last Update Posted (Actual)

May 6, 2020

Last Update Submitted That Met QC Criteria

May 5, 2020

Last Verified

May 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ERIBRAIN-IPC 2017-014
  • 2018-001027-40 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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