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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05696626




Registration number
NCT05696626
Ethics application status
Date submitted
13/01/2023
Date registered
25/01/2023
Date last updated
18/06/2024

Titles & IDs
Public title
Evaluation of Lasofoxifene Combined With Abemaciclib Compared With Fulvestrant Combined With Abemaciclib in Locally Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation
Scientific title
An Open Label, Randomized, Multicenter Study Comparing the Efficacy and Safety of the Combination of Lasofoxifene and Abemaciclib to the Combination of Fulvestrant and Abemaciclib for the Treatment of Pre- and Postmenopausal Women and Men With Locally Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation
Secondary ID [1] 0 0
SMX 22-002
Universal Trial Number (UTN)
Trial acronym
ELAINEIII
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Lasofoxifene in combination with abemaciclib
Treatment: Drugs - Fulvestrant in combination with abemaciclib

Experimental: Treatment - Pre- and Postmenopausal Women and Men with locally advanced or metastatic ER+/HER2- breast cancer who have disease progression on an AI in combination with either palbociclib or ribociclib as their first hormonal treatment for metastatic disease and who have an ESR1 mutation.

Active comparator: Reference Therapy - Pre- and Postmenopausal Women and Men with locally advanced or metastatic ER+/HER2- breast cancer who have disease progression on an AI in combination with either palbociclib or ribociclib as their first hormonal treatment for metastatic disease and who have an ESR1 mutation.


Treatment: Drugs: Lasofoxifene in combination with abemaciclib
5 mg/d of oral lasofoxifene plus oral abemaciclib 150 mg twice a day

Treatment: Drugs: Fulvestrant in combination with abemaciclib
Fulvestrant 500 mg intramuscular (IM) on Days 1, 15, and 29 and then once monthly thereafter plus oral abemaciclib 150 mg twice a day
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression free survival (PFS)
Timepoint [1] 0 0
Within approximately 3 years
Secondary outcome [1] 0 0
Objective response rate (ORR)
Timepoint [1] 0 0
Within approximately 3 years
Secondary outcome [2] 0 0
Overall survival (OS)
Timepoint [2] 0 0
Within approximately 3 years
Secondary outcome [3] 0 0
Clinical benefit rate (CBR)
Timepoint [3] 0 0
Within approximately 3 years
Secondary outcome [4] 0 0
Duration of response (DoR) in subjects with an objective response
Timepoint [4] 0 0
Within approximately 3 years
Secondary outcome [5] 0 0
Time to response (TTR) in subjects with an objective response
Timepoint [5] 0 0
Within approximately 3 years
Secondary outcome [6] 0 0
Time to cytotoxic chemotherapy
Timepoint [6] 0 0
Within approximately 3 years
Secondary outcome [7] 0 0
Quality of Life (QoL) evaluated using the Functional Assessment of Cancer Therapy-Breast Cancer-Endocrine Subscale (FACT B-ES)
Timepoint [7] 0 0
Within approximately 3 years
Secondary outcome [8] 0 0
Incidence of Adverse Events (AEs) and Serious AEs
Timepoint [8] 0 0
Within approximately 3 years

Eligibility
Key inclusion criteria
1. Pre- or postmenopausal women or men.
2. Locally advanced and/or metastatic ER+ breast cancer with radiological or clinical evidence of progression on an AI in combination with either palbociclib or ribociclib as their first hormonal treatment for metastatic disease.
3. Histological or cytological confirmation of ER+/HER2 - disease
4. No evidence of progression for at least 6 months on an AI/CDKi combination for advanced breast cancer.
5. At least 1 or more ESR1 point mutations in the ESR1 ligand binding domain as assessed in cell- free ctDNA obtained from a blood or breast cancer tissue.
6. Locally advanced or metastatic breast cancer with either measurable (according to RECIST 1.1) or non-measurable lesions.
7. Subjects may have received 1 cytotoxic chemotherapy regimen in the metastatic disease setting prior to study entry, but must have recovered from chemotherapy acute toxicity excluding alopecia and Grade 2 peripheral neuropathy.
8. Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1
9. Adequate organ function
10. Able to swallow tablets
11. Brain metastases are allowed only if the following 4 parameters hold:

1. Asymptomatic,
2. Definitively treated (e.g., radiotherapy, surgery),
3. Not requiring steroids up to 4 weeks before study treatment initiation, AND
4. Central nervous system disease stable for >3 months prior to registration as documented by magnetic resonance imagining (MRI).
12. Able to understand and voluntarily sign a written informed consent before any screening procedures.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Lymphangitic carcinomatosis involving the lung.
2. History of Grade 3 or Grade 4 interstitial lung disease (ILD) on previous therapy.
3. Visceral crisis in need of cytotoxic chemotherapy as assessed by the investigator.
4. Prior progression of disease on abemaciclib, fulvestrant, or other selective estrogen receptor degrader (SERD) therapy.
5. Subjects with a known hypersensitivity to fulvestrant or to any of the excipients
6. Radiotherapy within 30 days prior to Visit 0 (Day 1) except in case of localized radiotherapy for analgesic purposes or for lytic lesions at risk of fracture, which can then be completed within 7 days prior to Visit 0 (Day 1). Subjects must have recovered from radiotherapy toxicities prior to Visit 0 (Day 1).
7. Known RB1 mutations or deletions that in the opinion of the investigator confer resistance to CDK4/6i. (Screening for RB1 mutation is not required for entry.)
8. History of long QTc (Q-T interval corrected for heart rate) syndrome or a QTc of >480 msec.
9. History of a pulmonary embolus (PE), deep vein thrombosis (DVT), or any known thrombophilia.
10. Lasofoxifene is not recommended for use in subjects with conditions that place them at increased risk for VTEs (such as severe congestive heart failure [CHF] or prolonged immobilization).
11. On concomitant strong CYP3A4 inhibitors.
12. On strong and moderate CYP3A4 inducers.
13. Any significant co-morbidity that would impact the study or the subject's safety, including subjects with significant malabsorption.
14. Active systemic bacterial or fungal infection (requiring intravenous [IV] antibiotics or antifungals at the time of initiating study treatment).
15. Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV).
16. History of malignancy within the past 5 years (excluding breast cancer), except basal cell or squamous cell carcinoma of the skin curatively treated by surgery.
17. Positive serum pregnancy test (only if premenopausal).
18. Sexually active premenopausal women and men unwilling to use double-barrier contraception.
19. Women who are breast feeding
20. History of non-compliance to medical regimens.
21. Unwilling or unable to comply with the protocol.
22. Current participation in any clinical research trial involving an investigational drug or device within the last 30 days.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/10/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/06/2026
Actual
Sample size
Target
400
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Blacktown Hospital - Blacktown
Recruitment hospital [2] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [3] 0 0
Mater Misericordiae Ltd, South Brisbane - South Brisbane
Recruitment postcode(s) [1] 0 0
- Blacktown
Recruitment postcode(s) [2] 0 0
- Concord
Recruitment postcode(s) [3] 0 0
- South Brisbane
Recruitment outside Australia
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Nottingham
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Preston

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Sermonix Pharmaceuticals Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The goal of this clinical trial is to assess the efficacy, safety and tolerability of the combination of lasofoxifene and abemaciclib compared to fulvestrant and abemaciclib for the treatment of pre- and postmenopausal women and men who have previously received ribociclib or palbociclib-based treatment and have locally advanced or metastatic estrogen receptor positive (ER+)/human epidermal growth factor 2 negative (HER2-) breast cancer with an estrogen receptor 1 (ESR1) mutation.

The main question the study aims to answer is:

• To compare the efficacy of the combination of lasofoxifene and abemaciclib with that of fulvestrant and abemaciclib Participants will receive either receive 5 mg/d of oral lasofoxifene plus oral abemaciclib 150 mg twice a day or the combination of fulvestrant 500 mg intramuscular (IM) on Days 1, 15, and 29 and then once monthly thereafter plus oral abemaciclib 150 mg twice a day.
Trial website
https://clinicaltrials.gov/study/NCT05696626
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Sermonix Pharmaceuticals Study Inquiry
Address 0 0
Country 0 0
Phone 0 0
614-864-4919
Fax 0 0
Email 0 0
info@sermonixpharma.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05696626