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

Primary Purpose

Breast Cancer

Status

Terminated

Phase

Phase 2

Locations

United Kingdom

Study Type

Interventional

Intervention

Eribulin

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

Charing Cross Hopsital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single arm study

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

Full Information

NCT ID

NCT02681523

First Posted

February 10, 2016

Last Updated

January 18, 2021

Sponsor

Imperial College London

1. Study Identification

Unique Protocol Identification Number

NCT02681523

Brief Title

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

Acronym

ALERT

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2021

Overall Recruitment Status

Terminated

Why Stopped

Slow patient recruitment

Study Start Date

October 28, 2015 (Actual)

Primary Completion Date

July 24, 2018 (Actual)

Study Completion Date

July 24, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Imperial College London

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer

Keywords

Breast Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

8 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Single arm study

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Eribulin

Other Intervention Name(s)

Halaven

Primary Outcome Measure Information:

Title

Estimated Kaplan-Meier Progression Free Survival as Assessed by RECIST v1.1

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.

Time Frame

Fixed timepoints - 3, 6 and 9 months

Secondary Outcome Measure Information:

Title

Clinical Benefit Rate as Assessed by RECIST v1.1

Description

Time Frame

To be assessed at 3, 6 and 9 months.

Title

Safety and Tolerability

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.

Time Frame

Collected form consent to follow-up

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Laura Kenny

Organizational Affiliation

Consultant Medical Oncologist

Official's Role

Principal Investigator

Facility Information:

Facility Name

Charing Cross Hopsital

City

London

ZIP/Postal Code

W6 8RF

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

Not currently planned in the protocol.

Learn more about this trial

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

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