Breast CancerPhase 2ALERTNCT02681523
ALERT: A Phase II Study of Alternating Eribulin and Hormonal Therapy in Pre-treated ER+ve Breast Cancer.
A Phase 2 study testing Eribulin in people with Breast Cancer, run by Imperial College London at 1 site in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- 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
- 8 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 28 Oct 2015to 24 Jul 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 21Show fewer
- 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.
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Breast Cancer
- Being tested
- Eribulin
- Keywords
- Breast Cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EribulinDrug
Also called Halaven
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Eribulin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Estimated Kaplan-Meier Progression Free Survival as Assessed by RECIST v1.1
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.
Measured: Fixed timepoints - 3, 6 and 9 months
Secondary outcomes (2)
Clinical Benefit Rate as Assessed by RECIST v1.1
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.
Measured: To be assessed at 3, 6 and 9 months.
Safety and Tolerability
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.
Measured: Collected form consent to follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2016 (estimated)
- Study start28 Oct 2015
- Primary completion24 Jul 2018
- Study completion24 Jul 2018
Why it stopped: Slow patient recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Laura Kenny, Principal investigator, Consultant Medical Oncologist
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02681523
- Sponsor's protocol ID
- C/31/2014
- Other IDs
- 2014-004112-11, 2014
- Acronym
- ALERT
- Status last verified
- Aug 2024
- First submitted
- 10 Feb 2016
- Last updated
- 19 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Not currently planned in the protocol.
Publications
Allsopp RC, Guo Q, Page K, Bhagani S, Kasim A, Badman P, Kenny L, Stebbing J, Shaw JA. Circulating tumour DNA dynamics during alternating chemotherapy and hormonal therapy in metastatic breast cancer: the ALERT study. Breast Cancer Res Treat. 2024 Jul;206(2):377-385. doi: 10.1007/s10549-024-07316-8. Epub 2024 Apr 6.
PubMed 38581534
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ALERT: A Phase II Study of Alternating Eribulin and Hormonal Therapy in Pre-treated ER+ve Breast Cancer.
- ClinicalTrials.gov ID
- NCT02681523
- Acronym / sponsor ID
- ALERT / C/31/2014
- Conditions
- Breast Cancer
- Keywords
- Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow patient recruitment
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- 28 Oct 2015 (actual)
- Primary completion
- 24 Jul 2018 (actual)
- Study completion
- 24 Jul 2018 (actual)
- First posted
- 12 Feb 2016 (estimated)
- Results
- Posted 5 Feb 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single arm study | Experimental | Drug: Eribulin3 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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
Key exclusion criteria (12 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EribulinAlso: Halaven | Drug | Single arm study |
Primary outcome
Estimated Kaplan-Meier Progression Free Survival as Assessed by RECIST v1.1
Time frame: Fixed timepoints - 3, 6 and 9 months
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.
2 secondary outcomes
Clinical Benefit Rate as Assessed by RECIST v1.1
Time frame: To be assessed at 3, 6 and 9 months.
Safety and Tolerability
Time frame: Collected form consent to follow-up
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38581534Allsopp RC, Guo Q, Page K, Bhagani S, Kasim A, Badman P, Kenny L, Stebbing J, Shaw JA. Circulating tumour DNA dynamics during alternating chemotherapy and hormonal therapy in metastatic breast cancer: the ALERT study. Breast Cancer Res Treat. 2024 Jul;206(2):377-385. doi: 10.1007/s10549-024-07316-8. Epub 2024 Apr 6.
- Individual participant dataSharing planned: No. Not currently planned in the protocol.
Related trials for Breast Cancer
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Laura Kenny principal investigator
Consultant Medical Oncologist
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Eribulin in people with Breast Cancer, run by Imperial College London at 1 site in United Kingdom.
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 21 inclusion and 12 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: stopped early, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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?
Yes. Results are posted in the registry (first posted 5 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Estimated Kaplan-Meier Progression Free Survival as Assessed by RECIST v1.1 (time frame: Fixed timepoints - 3, 6 and 9 months). 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 NCT02681523, which also lists 1 linked publication.
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 19 Sep 2024.