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Metastatic Breast CancerPhase 2ERIBRAINNCT03637868

Eribulin in Brain Metastases From HER2-negative Breast Cancer

A Phase 2 study testing Eribulin in people with Metastatic Breast Cancer, run by Institut Paoli-Calmettes at 7 sites in France.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

To evaluate the efficacy of eribulin for treatment of HER2-negative breast cancer brain metastases (BCBM) Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Breast Cancer
What is being tested?
Eribulin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
7 sitesFrance
Study dates
26 Feb 2019to 14 Apr 2020
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • At least 18 years of age.
  • Life expectancy of 3 months or longer.
  • ECOG (Eastern Cooperative Oncology Group) performance status of 0, 1, or 2.
  • HER2-negative (IHC 0/1+ or 2+ and in situ hybridization negative) metastatic breast cancer
  • 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)
  • At least 2 weeks washout period post chemotherapy, targeted or biologic therapy, or radiation therapy is required prior to study entry
Show all 20Show fewer
  • 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.
  • 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.
  • 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

Who cannot join

  • Prior therapy with eribulin.
  • 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)
  • 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
Show all 20Show fewer
  • 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.
  • Patient candidate to SRS and or surgical resection
  • Major clinical symptoms requiring immediate WBRT as defined by "local tumor board"
  • Increase in corticosteroid dose in the week prior to baseline brain MRI
  • Patients with pacemaker or implantable cardioverter-defibrillator devices incompatible with MRI assessment.
  • Contraindication to Gadolinium infusion.
  • Treatment ongoing with other chemotherapy, hormonal therapy, immunotherapy, other investigational agents, or biologic agents for the treatment of cancer except bisphosphonates or denosumab.
  • Pregnant or breast-feeding patients
  • Women of child-bearing potential without effective contraception method.
  • Patient unable to express their consent.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

France7 sites

  • Institut de Cancerologie de L'Ouest - Paul Papin

    Angers

  • Institut Sainte Catherine

    Avignon

  • CHU Besançon

    Besançon

  • Institut Paoli-Calmettes

    Marseille, 13009

  • Institut Du Cancer de Montpellier

    Montpellier, 34298

  • Institut De Cancérologie de l'Ouest

    Saint-Herblain

  • Institut de Cancerologie de Lorraine Alexis Vautrin

    Vandœuvre-lès-Nancy

Other trials in France

About this study

Official title: 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)

Read the 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
Being tested
Eribulin
Keywords
HER2-negative breast cancer, brain metastases
Medical subject headings
Breast Neoplasms, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EribulinDrug

    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.

Study groups in NCT03637868
Study groupRoleWhat they receive
EribulinExperimentaleribulin 1.4 mg/m² administered intravenously between 6 and 7 cycles.
Receives: Drug: Eribulin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Efficacy of eribulin for treatment of HER2-negative BCBM

    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)

    Measured: from inclusion until 30 days after completion of treatment

Secondary outcomes (6)

  1. Safety of Eribulin in this population

    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

    Measured: from Eribulin initiation until 30 days after completion of treatment

  2. Time to WBRT (cohort A and B)

    Time to WBRT will be defined as the time from Eribulin initiation to WBRT start

    Measured: from Eribulin initiation to the time of the first dose of whole brain radiation therapy - up to 28 months

  3. CNS progression-free survival

    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

    Measured: from Eribulin initiation until the date of first documented CNS disease progression or date of death from any cause - up to 28 months

  4. Overall survival

    Overall survival will be defined as the time from Eribulin initiation to death from any cause

    Measured: from Eribulin initiation to death

  5. Change in cognitive function

    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)

    Measured: From Eribulin initiation up to 7 days after study treatment discontinuation

  6. Quality of life measured by Functional Assessment of Cancer Therapy-Brain Metastasis

    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

    Measured: From Eribulin initiation up to 7 days after study treatment discontinuation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Aug 2018
  2. Study start26 Feb 2019
  3. Primary completion14 Apr 2020
  4. Study completion14 Apr 2020

Why it stopped: no enrollment

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Prospective, national, multicenter, open-label, uncontrolled, multi-cohort phase II trial
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03637868
Sponsor's protocol ID
ERIBRAIN-IPC 2017-014
Other IDs
2018-001027-40, 2018
Acronym
ERIBRAIN
Status last verified
May 2020
First submitted
6 Aug 2018
Last updated
6 May 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Arslan C, Dizdar O, Altundag K. Chemotherapy and biological treatment options in breast cancer patients with brain metastasis: an update. Expert Opin Pharmacother. 2014 Aug;15(12):1643-58. doi: 10.1517/14656566.2014.929664.

    PubMed 25032884

  • Bart J, Nagengast WB, Coppes RP, Wegman TD, van der Graaf WT, Groen HJ, Vaalburg W, de Vries EG, Hendrikse NH. Irradiation of rat brain reduces P-glycoprotein expression and function. Br J Cancer. 2007 Aug 6;97(3):322-6. doi: 10.1038/sj.bjc.6603864. Epub 2007 Jul 3.

    PubMed 17609666

  • Bartsch R, Fromm S, Rudas M, Wenzel C, Harbauer S, Roessler K, Kitz K, Steger GG, Weitmann HD, Poetter R, Zielinski CC, Dieckmann K. Intensified local treatment and systemic therapy significantly increase survival in patients with brain metastases from advanced breast cancer - a retrospective analysis. Radiother Oncol. 2006 Sep;80(3):313-7. doi: 10.1016/j.radonc.2006.08.001. Epub 2006 Sep 7.

    PubMed 16959347

  • Chang AY, Ying XX. Brain Metastases from Breast Cancer and Response to Treatment with Eribulin: A Case Series. Breast Cancer (Auckl). 2015 May 24;9:19-24. doi: 10.4137/BCBCR.S21176. eCollection 2015.

    PubMed 26052228

  • Cortes J, O'Shaughnessy J, Loesch D, Blum JL, Vahdat LT, Petrakova K, Chollet P, Manikas A, Dieras V, Delozier T, Vladimirov V, Cardoso F, Koh H, Bougnoux P, Dutcus CE, Seegobin S, Mir D, Meneses N, Wanders J, Twelves C; EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician's Choice Versus E7389) investigators. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet. 2011 Mar 12;377(9769):914-23. doi: 10.1016/S0140-6736(11)60070-6. Epub 2011 Mar 2.

    PubMed 21376385

  • Jimeno A. Eribulin: rediscovering tubulin as an anticancer target. Clin Cancer Res. 2009 Jun 15;15(12):3903-5. doi: 10.1158/1078-0432.CCR-09-1023. Epub 2009 Jun 9.

    PubMed 19509144

  • Joly F, Lange M, Rigal O, Correia H, Giffard B, Beaumont JL, Clisant S, Wagner L. French version of the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) version 3. Support Care Cancer. 2012 Dec;20(12):3297-305. doi: 10.1007/s00520-012-1439-2. Epub 2012 May 2.

    PubMed 22549504

  • Jordan MA, Kamath K, Manna T, Okouneva T, Miller HP, Davis C, Littlefield BA, Wilson L. The primary antimitotic mechanism of action of the synthetic halichondrin E7389 is suppression of microtubule growth. Mol Cancer Ther. 2005 Jul;4(7):1086-95. doi: 10.1158/1535-7163.MCT-04-0345.

    PubMed 16020666

  • Kaufman PA, Awada A, Twelves C, Yelle L, Perez EA, Velikova G, Olivo MS, He Y, Dutcus CE, Cortes J. Phase III open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2015 Feb 20;33(6):594-601. doi: 10.1200/JCO.2013.52.4892. Epub 2015 Jan 20.

    PubMed 25605862

  • Lin NU, Lee EQ, Aoyama H, Barani IJ, Barboriak DP, Baumert BG, Bendszus M, Brown PD, Camidge DR, Chang SM, Dancey J, de Vries EG, Gaspar LE, Harris GJ, Hodi FS, Kalkanis SN, Linskey ME, Macdonald DR, Margolin K, Mehta MP, Schiff D, Soffietti R, Suh JH, van den Bent MJ, Vogelbaum MA, Wen PY; Response Assessment in Neuro-Oncology (RANO) group. Response assessment criteria for brain metastases: proposal from the RANO group. Lancet Oncol. 2015 Jun;16(6):e270-8. doi: 10.1016/S1470-2045(15)70057-4. Epub 2015 May 27.

    PubMed 26065612

  • Lu J, Steeg PS, Price JE, Krishnamurthy S, Mani SA, Reuben J, Cristofanilli M, Dontu G, Bidaut L, Valero V, Hortobagyi GN, Yu D. Breast cancer metastasis: challenges and opportunities. Cancer Res. 2009 Jun 15;69(12):4951-3. doi: 10.1158/0008-5472.CAN-09-0099. Epub 2009 May 26. No abstract available.

    PubMed 19470768

  • Matsuoka H, Tsurutani J, Tanizaki J, Iwasa T, Komoike Y, Koyama A, Nakagawa K. Regression of brain metastases from breast cancer with eribulin: a case report. BMC Res Notes. 2013 Dec 18;6:541. doi: 10.1186/1756-0500-6-541.

    PubMed 24350786

  • Narayan S, Carlson EM, Cheng H, Condon K, Du H, Eckley S, Hu Y, Jiang Y, Kumar V, Lewis BM, Saxton P, Schuck E, Seletsky BM, Tendyke K, Zhang H, Zheng W, Littlefield BA, Towle MJ, Yu MJ. Novel second generation analogs of eribulin. Part III: Blood-brain barrier permeability and in vivo activity in a brain tumor model. Bioorg Med Chem Lett. 2011 Mar 15;21(6):1639-43. doi: 10.1016/j.bmcl.2011.01.096. Epub 2011 Jan 26.

    PubMed 21324687

  • Pivot X, Marme F, Koenigsberg R, Guo M, Berrak E, Wolfer A. Pooled analyses of eribulin in metastatic breast cancer patients with at least one prior chemotherapy. Ann Oncol. 2016 Aug;27(8):1525-31. doi: 10.1093/annonc/mdw203. Epub 2016 May 13.

    PubMed 27177860

  • Qin DX, Zheng R, Tang J, Li JX, Hu YH. Influence of radiation on the blood-brain barrier and optimum time of chemotherapy. Int J Radiat Oncol Biol Phys. 1990 Dec;19(6):1507-10. doi: 10.1016/0360-3016(90)90364-p.

    PubMed 2262373

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Eribulin in people with Metastatic Breast Cancer, run by Institut Paoli-Calmettes at 7 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 6 May 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Efficacy of eribulin for treatment of HER2-negative BCBM (time frame: from inclusion until 30 days after completion of treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03637868, which also lists 19 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2020.

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