Clinical Trials /

Eribulin in Brain Metastases From HER2-negative Breast Cancer

NCT03637868

Description:

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

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: ERIBRAIN-IPC 2017-014
  • SECONDARY ID: 2018-001027-40
  • NCT ID: NCT03637868

Conditions

  • Metastatic Breast Cancer

Interventions

DrugSynonymsArms
EribulinEribulin

Purpose

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

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
    

Trial Arms

NameTypeDescriptionInterventions
EribulinExperimentaleribulin 1.4 mg/m² administered intravenously between 6 and 7 cycles.
  • Eribulin

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Efficacy of eribulin for treatment of HER2-negative BCBM
Time Frame:from inclusion until 30 days after completion of treatment
Safety Issue:
Description: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)

Secondary Outcome Measures

Measure:Safety of Eribulin in this population
Time Frame:from Eribulin initiation until 30 days after completion of treatment
Safety Issue:
Description: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
Measure: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
Safety Issue:
Description:Time to WBRT will be defined as the time from Eribulin initiation to WBRT start
Measure: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
Safety Issue:
Description: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
Measure:Overall survival
Time Frame:from Eribulin initiation to death
Safety Issue:
Description:Overall survival will be defined as the time from Eribulin initiation to death from any cause
Measure:Change in cognitive function
Time Frame:From Eribulin initiation up to 7 days after study treatment discontinuation
Safety Issue:
Description: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)
Measure: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
Safety Issue:
Description: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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Institut Paoli-Calmettes

Trial Keywords

  • HER2-negative breast cancer
  • brain metastases

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