Eribulin in Brain Metastases From HER2-negative Breast Cancer

NCT03637868 | Withdrawn Phase 2

• 2 other identifiers: ERIBRAIN-IPC 2017-0142018-001027-40
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 7

Brief Summary

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

Conditions

Metastatic Breast Cancer

Keywords

HER2-negative breast cancer; brain metastases

Outcome Measures

Primary Outcomes (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)

  from inclusion until 30 days after completion of treatment

Secondary Outcomes (6)

• Safety of Eribulin in this population

  from Eribulin initiation until 30 days after completion of treatment

• Time to WBRT (cohort A and B)

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

• CNS progression-free survival

  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

  from Eribulin initiation to death

• Change in cognitive function

  From Eribulin initiation up to 7 days after study treatment discontinuation

Other Outcomes (6)

• Progression-free survival for non-CNS disease

  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)

  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

  from Eribulin initiation until 30 days after completion of treatment

Study Arms (1)

Eribulin

EXPERIMENTAL

eribulin 1.4 mg/m² administered intravenously between 6 and 7 cycles.

Drug: Eribulin

Interventions

Eribulin DRUG

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.

Eribulin

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Institut Paoli-Calmettes: lead
• Eisai Inc.: collaborator

Study Sites (7)

Institut de Cancerologie de L'Ouest - Paul Papin

Angers, France

Location

Institut Sainte Catherine

Avignon, France

Location

CHU Besançon

Besançon, France

Location

Institut Paoli-Calmettes

Marseille, 13009, France

Location

Institut Du Cancer de Montpellier

Montpellier, 34298, France

Location

Institut De Cancérologie de l'Ouest

Saint-Herblain, France

Location

Institut de Cancerologie de Lorraine Alexis Vautrin

Vandœuvre-lès-Nancy, France

Location

Related Publications (19)

• 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.

  PMID: 25032884 BACKGROUND

• 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.

  PMID: 17609666 BACKGROUND

• 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.

  PMID: 16959347 BACKGROUND

• 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.

  PMID: 26052228 BACKGROUND

• 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.

  PMID: 21376385 BACKGROUND

• 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.

  PMID: 19509144 BACKGROUND

• 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.

  PMID: 22549504 BACKGROUND

• 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.

  PMID: 16020666 BACKGROUND

• 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.

  PMID: 25605862 BACKGROUND

• 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.

  PMID: 26065612 BACKGROUND

• 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.

  PMID: 19470768 BACKGROUND

• 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.

  PMID: 24350786 BACKGROUND

• 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.

  PMID: 21324687 BACKGROUND

• 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.

  PMID: 27177860 BACKGROUND

• 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.

  PMID: 2262373 BACKGROUND

• Schwartz LH, Litiere S, de Vries E, Ford R, Gwyther S, Mandrekar S, Shankar L, Bogaerts J, Chen A, Dancey J, Hayes W, Hodi FS, Hoekstra OS, Huang EP, Lin N, Liu Y, Therasse P, Wolchok JD, Seymour L. RECIST 1.1-Update and clarification: From the RECIST committee. Eur J Cancer. 2016 Jul;62:132-7. doi: 10.1016/j.ejca.2016.03.081. Epub 2016 May 14.

  PMID: 27189322 BACKGROUND

• Thavarajah N, Bedard G, Zhang L, Cella D, Beaumont JL, Tsao M, Barnes E, Danjoux C, Sahgal A, Soliman H, Chow E. Psychometric validation of the functional assessment of cancer therapy--brain (FACT-Br) for assessing quality of life in patients with brain metastases. Support Care Cancer. 2014 Apr;22(4):1017-28. doi: 10.1007/s00520-013-2060-8. Epub 2013 Nov 28.

  PMID: 24287508 BACKGROUND

• Toth K, Vaughan MM, Peress NS, Slocum HK, Rustum YM. MDR1 P-glycoprotein is expressed by endothelial cells of newly formed capillaries in human gliomas but is not expressed in the neovasculature of other primary tumors. Am J Pathol. 1996 Sep;149(3):853-8.

  PMID: 8780389 BACKGROUND

• Zhang RD, Price JE, Fujimaki T, Bucana CD, Fidler IJ. Differential permeability of the blood-brain barrier in experimental brain metastases produced by human neoplasms implanted into nude mice. Am J Pathol. 1992 Nov;141(5):1115-24.

  PMID: 1443046 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms; Brain Neoplasms

Interventions

eribulin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Renaud Sabatier, MD

  Institut Paoli-Calmettes

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, national, multicenter, open-label, uncontrolled, multi-cohort phase II trial

Study Record Dates

• First Submitted: August 6, 2018
• First Posted: August 20, 2018
• Study Start: February 26, 2019
• Primary Completion: April 14, 2020
• Study Completion: April 14, 2020
• Last Updated: May 6, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (7)