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.
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
- ORG STUDY ID:
C/31/2014
- SECONDARY ID:
2014-004112-11
- NCT ID:
NCT02681523
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Eribulin | Halaven | Single arm study |
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 Aromatase Inhibitor (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 circulating free DNA (cfDNA) termed circulating tumor DNA (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. | |
Eligibility Criteria
Inclusion Criteria:
- 1. Written informed consent prior to admission to this study
- 2. Aged 18≥over
- 3. Histologically confirmed ER+ve metastatic breast cancer according to local criteria
- 4. Eastern Cooperative Oncology Group (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)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 Upper Limit of Normal (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.
- Alkaline Phosphatase Level (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 Human Epidermal Growth Factor Receptor 2 (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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | Female |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Estimated Kaplan-Meier Progression Free Survival as Assessed by RECIST v1.1 |
| Time Frame: | Fixed timepoints - 3, 6 and 9 months |
| Safety Issue: | |
| Description: | Estimated Kaplan-Meier Progression free survival (PFS) to be defined as time from study entry to first evidence of disease progression or death due to any cause, as assessed by RECIST v1.0. |
Secondary Outcome Measures
| Measure: | Clinical Benefit Rate as Assessed by RECIST v1.1 |
| Time Frame: | To be assessed at 3, 6 and 9 months. |
| Safety Issue: | |
| Description: | Clinical benefit rate (CBR), defined as the proportion of patients whose best overall response according to Response Evaluation Criteria in Solid Tumours (RECIST), v1.0 is either a complete response, partial response or stable disease for a least 6 months. |
| Measure: | Safety and Tolerability |
| Time Frame: | Collected form consent to follow-up |
| Safety Issue: | |
| Description: | Safety and Tolerability were assessed by adverse events (AEs) and serious adverse events (SAEs) according the Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03. |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Terminated |
| Lead Sponsor: | Imperial College London |
Trial Keywords
Last Updated
February 5, 2021
