Clinical Trials /

ALERT: A Phase II Study of Alternating Eribulin and Hormonal Therapy in Pre-treated ER+ve Breast Cancer.

NCT02681523

Description:

A single centre, single arm phase II study of alternating eribulin and hormonal therapy in 12 patients with locally advanced or metastatic breast cancer who have received at least one hormonal therapy and at least one chemotherapy in the metastatic setting.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 2

Trial Eligibility

Document

ALERT: A Phase II Study of Alternating <span class="go-doc-concept go-doc-intervention">Eribulin</span> and Hormonal Therapy in Pre-treated ER+ve Breast Cancer.

Title

  • Brief Title: ALERT: A Phase II Study of Alternating Eribulin and Hormonal Therapy in Pre-treated ER+ve Breast Cancer.
  • Official Title: ALERT: A Phase II Study of Alternating Eribulin and Hormonal Therapy in Pre-treated ER+ve Breast Cancer.
  • Clinical Trial IDs

    NCT ID: NCT02681523

    ORG ID: C/31/2014

    Trial Conditions

    Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    Eribulin Halaven Single arm study

    Trial Purpose

    A single centre, single arm phase II study of alternating eribulin and hormonal therapy in
    12 patients with locally advanced or metastatic breast cancer who have received at least one
    hormonal therapy and at least one chemotherapy in the metastatic setting.

    Detailed Description

    12 patients with locally advanced or metastatic breast cancer who have received at least one
    hormonal therapy and at least one chemotherapy in the metastatic setting will be enrolled to
    receive treatment. Once patients are consented and have completed on study screening,
    eribulin and AI treatment will be alternated for up to 9 months, until disease progression
    or unacceptable toxicities, whichever is sooner. Patients will then attend a safety
    follow-up visit 4 weeks after completing treatment.

    Eribulin (Halaven) is a non-taxane microtubule dynamics inhibitor. Eribulin inhibits the
    growth phase of microtubules without affecting the shortening phase and sequesters tubulin
    into non-productive aggregates. Eribulin exerts its effects via a tubulin-based antimitotic
    mechanism leading to G2/M cell-cycle block, disruption of mitotic spindles, and, ultimately,
    apoptotic cell death after prolonged mitotic blockage.

    Eribulin is licenced for the treatment of patients with locally advanced or metastatic
    breast cancer who have previously received at least one chemotherapeutic regimen for the
    treatment of 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.

    The aim of this study is to alternate eribulin and aromatase inhibitors, examining whether
    there may be breakthrough relapse during the AI therapy or on the other hand we can extend
    the duration that eribulin may be used for. Importantly, blood based biomarkers, the tumour
    derived fraction of cfDNA (ctDNA), and circulating tumour cells will be measured. A major
    aim of this study is to test whether biomarkers fluctuate between chemotherapy and AI
    treatment in the setting of advanced breast cancer.

    Trial Arms

    Name Type Description Interventions
    Single arm study Experimental 3 x 3 weekly cycles at the recommended dose of eribulin as the ready to use solution, 1.23 mg/m2, administered intravenously over 2-5 minutes on days 1 and 8 of every 21 day cycle. This will then be followed by 9 weeks of AI treatment, to be followed again by 3 x 3 weekly cycles of eribulin and 9 weeks AI treatment. Patients will remain on treatment for up to 9 months, or until disease progression or unacceptable toxicities, whichever is sooner. Eribulin

    Eligibility Criteria

    Inclusion Criteria:

    - 1. Written informed consent prior to admission to this study

    - 2. Aged 18over

    - 3. Histologically confirmed ER+ve metastatic breast cancer according to local
    criteria

    - 4. ECOG performance status 0 - 2

    - 5. Have progressed after at least one hormonal therapy regime and at least one
    chemotherapy regime for advanced disease

    - 6. Patients must have had prior treatment with an anthracycline and a taxane (either
    sequential or in combination) unless patients were not suitable for these treatments.
    This treatment can be in the adjuvant setting

    - 7. Measurable sites of locally advanced and/or metastatic disease that can be
    accurately assessed by CT/MRI scan at baseline (RECIST v1.1)

    - 8. Life expectancy of 6 months

    - 9. Adequate organ function, as defined by:

    - Haemoglobin (Hb) 9 g/dL

    - Absolute Neutrophil Count (ANC) 1.5 x 109/L

    - Platelet count (Plts) 100 x 109/L

    - White Blood Cell (WBC) 3.0 x 109/L

    - Serum albumin 1.5 ULN

    - Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) 3 x ULN if
    no demonstrable liver metastases or 5 x ULN in the presence of liver
    metastases.

    - ALP 5 x ULN

    - Total bilirubin 1.5 x ULN if no demonstrable liver metastases or 3 x ULN in
    the presence of liver metastases

    - Creatinine 1.5 x ULN or creatinine clearance >50ml/min

    - 10. Postmenopausal as defined by age >50, no menstruation for >2 years, previous
    oophorectomy or lab results confirming this status

    - 11. Premenopausal if has been subject to ovarian ablation/ suppression at least 3
    weeks prior to commencing AI therapy

    - RECIST v1.1 updated and now considers bone metastasis with an identifiable soft
    tissue mass to be measurable disease. Therefore, patients with bone metastasis
    are eligible, provided they have evaluable disease.

    Exclusion Criteria:

    - 1.Triple negative or HER2 positive cancer

    - 2. Hypersensitivity to the active substance or to any of its excipients

    - 3. History of another primary malignancy within 5 years prior to starting study
    treatment, except adequately treated basal or squamous cell carcinoma of the skin,
    carcinoma in site and the disease under study

    - 4. Evidence of uncontrolled active infection

    - 5. Severe hepatic impairment (Child-Pugh C)

    - 6. Evidence of significant medical condition or laboratory finding which, in the
    opinion of the Investigator, makes it undesirable for the patient to participate in
    the trial

    - 7. Concurrent therapy with any other investigational agent or everolimus

    - 8. Concomitant use within 14 days prior to commencement of study treatment of any
    investigational agent

    - 9. Uncontrolled abnormalities of serum potassium, sodium, calcium (corrected)
    phosphate or magnesium levels

    - 10. Pregnant or lactating women. Effective non-hormonal contraception is mandatory
    for all patients of reproductive potential

    - 11. Evidence of ovarian activity

    - 12. Prior eribulin therapy

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    Progression free survival as assessed by RECIST v1.1

    Secondary Outcome Measures

    Clinical benefit rate as assessed by RECIST v1.1

    Trial Keywords