Medical Imaging to Re-evaluate Elacestrant Clinical Usage (IRENA)

August 6, 2026 updated by: Jules Bordet Institute

Imaging to Re-evaluate Elacestrant Clinical Application

The goal of this clinical trial is to evaluate whether elacestrant, an oral selective oestrogen receptor degrader, can improve outcomes in patients with oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer without detectable ESR1 mutation after progression on endocrine therapy plus a CDK4/6 inhibitor.

The study aims to answer two key questions:

  • Does [18F]-fluor-oestradiol positron emission tomography/computed tomography (18F-FES-PET/CT) result (homogeneous vs. heterogeneous) determine the efficacy of elacestrant in participants with advanced/metastatic ER-positive breast cancer and ESR1-mut-nd?
  • Does 18F-FES-PET/CT imaging predict patient outcomes, including progression-free survival, overall survival, or tumor response?

There is no comparison group in this study. All participants receive elacestrant. Researchers will compare outcomes in people who have different levels of estrogen-receptor heterogeneity on FES-PET/CT imaging.

Participants in the study will:

  • Take elacestrant 345 mg orally once a day, in 28-day treatment cycles (the dose may be lowered to 258 mg if needed due to side effects).
  • Undergo 18F-FES-PET/CT and 18F-FDG-PET/CT imaging both at the beginning of the study and as part of routine clinical evaluation every 8 weeks
  • Undergo blood sample collection every 8 weeks
  • If selected for a sub-study, undergo an additional FES-PET/CT scan 4 weeks after starting treatment

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

160

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age ≥ 18 years old
  2. ECOG performance status ≤ 1
  3. Must have histologically or cytologically confirmed diagnosis of breast cancer with evidence of locally advanced disease not amenable to therapy with curative intent or metastatic disease not amenable to curative therapy.
  4. Documentation of ER-positive (≥10% positive stained cells) and HER2 negative (0-1+ by immunohistochemistry [IHC] or 2+ and negative by in situ hybridization [ISH] test) advanced or metastatic breast cancer according to the most recent American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines as per local assessment. ER-positive/HER2-negative status should be confirmed in metastatic setting, with exception of patients with bone and lung only disease, where this might not possible.
  5. Must be appropriate candidates for endocrine monotherapy.

  6. Must have previously received no more than 1 line of endocrine therapy:

    • a) Radiological or objective evidence of disease progression on prior treatment with a CDK4/6 inhibitor in combination with endocrine therapy (either an aromatase inhibitor or fulvestrant) for advanced disease after at least 12 months of treatment.
    • b) Patients receiving CDK4/6 inhibitor-based therapy in the adjuvant setting are also eligible provided that disease progression is confirmed after finishing treatment with CDK4/6 inhibitor but no more than 12 months following CDK4/6 inhibitor treatment completion in this scenario, this will count as 1 line of ET for mBC.
  7. ESR1 mutation not detected, test performed after ET plus CDK4/6 inhibitor. This local determination will be performed in blood using a validated assay.

  8. No contraindications to perform 18F-FES-PET/CT.

    - a) Patients will not be selected when treated with SERMs or SERDs ≤ 5 weeks prior to inclusion as these drugs interfere with the accessibility of the ER.

  9. Life expectancy ≥ 6 months.

  10. At screening FDG-PET/CT at least two "target" lesions are required to fulfil the following criteria:

    • a) anatomically transaxial diameter ≥ 1.5 cm AND
    • b) metabolically assessable with a maximum standard uptake value corrected for lean body mass (SUVmax) ≥ 1.5 x SUVmean + 2 standard deviations (SD) of the liver measured in a 3-cm-diameter spherical volume of interest (VOI) in normal liver parenchyma.
    • c) In case of suspected liver metastasis, a lesion should have a SUVmax ≥ 2 x SUVmean + 3 SD of the blood pool measured in a 1 cm-diameter VOI within descending thoracic aorta. Lesions pre-treated with irradiation are not eligible for consideration as "target" lesions.

  11. Female participants must be post-menopausal women, defined by 1 of the following criteria:

    • a) Prior bilateral oophorectomy (≥ 28 days prior to Day 1 of treatment).
    • b) Age ≥ 60 years with amenorrhea ≥ 1 year since last menses.
    • c) Age < 60 years: i. Cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; OR ii. serum oestradiol and/or FSH levels within the laboratory's reference range for post-menopausal females
    • d) Pre- or perimenopausal women, who do not meet the criteria for post-menopausal status must be concurrently receiving a LHRH analogue (goserelin), as per standard of care, for at least 28 days (if shorter, post-menopausal levels of serum oestradiol/FSH must be confirmed analytically) prior to study enrolment and are planning to continue LHRH agonist treatment during the study.
  12. Resolution of all toxic effects of prior therapies or surgical procedures to Grade ≤ 1 (except for toxicities not considered a safety risk for the patient at Investigator's discretion).

  13. Adequate organ function as defined below:

    • a) Haematologic function: i. Absolute neutrophil count ≥ 1.0 x 109/L. ii. Platelet count ≥ 75 x 109/L. iii. Haemoglobin ≥ 9.0 g/dL.
    • b) Renal function: i. Estimated glomerular filtration rate ≥30 mL/min/1.73 m2 or creatinine. clearance calculated by Cockcroft-Gault equation ≥ 30 mL/min.
    • c) Hepatic function i. Alanine aminotransferase (ALT) ≤ 3x upper limit of normal (ULN; in the presence of liver metastases, ALT ≤ 5x ULN).

    ii. Total bilirubin ≤ ULN or total bilirubin ≤ 1.5x ULN with direct bilirubin ≤ ULN of the laboratory in participants with documented Gilbert's Syndrome.

    - d) Chemistry i. Potassium, sodium, calcium (corrected for albumin), magnesium, and phosphorus NCI CTCAE v6.0 Grade ≤ 1. If screening assessments are abnormal, chemistry assessments may be repeated up to 2 times; participants may receive appropriate supplementation or treatment (e.g., for hypercalcemia) prior to re-assessment e) Coagulation i. International normalized ratio (INR) ≤ 1.5

  14. Subject is willing and able to comply with the protocol for the duration of the study including treatment and scheduled visits and examinations.

  15. Signed Informed Consent Form (ICF) obtained prior to any study related procedure.

    Inclusion criterion applicable to FRANCE only:

  16. Affiliated to the French Social Security System (applicable only to participants treated in France)

Exclusion Criteria:

  1. Prior treatment with elacestrant, or an investigational SERD or ER antagonist.
  2. Prior chemotherapy for advanced or metastatic disease.

  3. Prior anti-cancer or investigational drug treatment within the following windows:

    • a) Fulvestrant treatment (last injection) < 5 weeks before first dose of study drug.
    • b) Any other endocrine therapy < 14 days before first dose of study drug.
    • c) Chemotherapy or other anti-cancer therapy < 21 days before first dose of study drug.
    • d) Any investigational anti-cancer drug therapy < 28 days or 5 half-lives (whichever is shorter) before the first dose of study drug.
  4. Radiation therapy (other than CNS directed) within 14 days before the first dose of study drug. CNS directed radiation therapy within 28 days before the first dose of study drug.
  5. Active or newly diagnosed CNS metastases, including meningeal carcinomatosis. Note: Patients with stable brain or subdural metastases are allowed if the subject has completed local therapy and was on a stable or decreasing dose of corticosteroids at pre-study treatment period baseline for management of brain metastasis for at least 4 weeks before starting treatment in this study. Any signs (e.g., radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment. If anticonvulsant medication is required, participants must be stable on a non-enzyme inducing anticonvulsant regimen (Appendix 1).
  6. Participants with advanced, symptomatic visceral spread, that are at risk of life-threatening complications in the short term, including massive uncontrolled effusions (peritoneal, pleural, pericardial), pulmonary lymphangitis, or liver involvement >50%.
  7. Intact uterus with a history of endometrial intraepithelial neoplasia (atypical endometrial hyperplasia or higher-grade lesion).
  8. Diagnosis of any other malignancy within 5 years before enrollment, except for adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or second primary breast cancer.
  9. Any of the following within 6 months before enrolment: myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE v6.0 Grade ≥2, prolonged QTcF ≥ Grade 2 (i.e., > 480 msec), uncontrolled atrial fibrillation of any grade, coronary/peripheral artery bypass graft, heart failure ≥ Class II as defined by the New York Heart Association guidelines, or cerebrovascular accident including transient ischemic attack.

  10. Coagulopathy or any history of coagulopathy within the past 6 months, including history of deep vein thrombosis or pulmonary embolism. However, participants with the following conditions will be allowed to participate:

    • a) Adequately treated catheter-related venous thrombosis occurring > 28 days prior to the first dose of study drug.
    • b) Treatment with an anticoagulant, e.g., warfarin or heparin, for a thrombotic event occurring > 6 months before enrolment, or for an otherwise stable and allowed medical condition (e.g., well controlled atrial fibrillation), provided dose and coagulation parameters (as defined by local standard of care) are stable for at least 28 days prior to the first dose of study drug and provided that an AI would be an appropriate therapy for the subject.
  11. Known difficulty in tolerating oral medications or conditions which would impair absorption of oral medications such as: uncontrolled nausea or vomiting (i.e., CTCAE ≥ Grade 3 despite antiemetic therapy), ongoing gastrointestinal obstruction/motility disorder, malabsorption syndrome, or prior gastric bypass.
  12. Unable or unwilling to avoid prescription medications, over-the-counter medications, dietary/herbal supplements (e.g., St. John's wort), and/or foods (e.g., grapefruit, pomelos, star fruit, Seville oranges and their juices) that are moderate/strong inhibitors or inducers of CYP3A4 activity (Appendix 1). Participation will be allowed if the medication, supplements, and/or foods are discontinued for at least 5 half-lives or 14 days (whichever is longer) prior to initiation of study treatment study enrolment and for the duration of the study.
  13. Major surgery < 28 days before the first dose of study drug
  14. Pregnant and/or lactating women, or intending to become pregnant during the study.
  15. Women of childbearing potential refusing to use 1 highly effective method of contraception prior study entry, during the course of the study and at least 120 days after the last administration of study treatment.
  16. Men with childbearing potential partner refusing to use condom during the course of this study and for at least 120 days after the last administration of the study treatment.
  17. Participant with a significant medical, neuro-psychiatric, or surgical condition, currently uncontrolled by treatment, which, in the principal investigator's opinion, may interfere with completion of the study.

  18. Known hypersensitivity reactions to the study drugs or to any excipients.

    Exclusion criterion applicable to FRANCE ONLY:

  19. Vulnerable persons according to the article L.1121-6 of the "Code de la Santé Publique" (CSP), adults who are the subject of a measure of legal protection or unable to express their consent according to article L.1121-8 of the CSP.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Elacestrant Treatment for ER-Positive, HER2-Negative Breast Cancer Without ESR1 Mutation
Drug: Elacestrant
Elacestrant is an orally available tetrahydronaphthalene compound that acts as selective oestrogen receptor alpha (ERα) antagonist with receptor degrading activity (e.g., selective oestrogen receptor degrader, SERD) and is being developed as a monotherapy agent and in combinations for the treatment of oestrogen receptor (ER) positive breast cancer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival in participants with ESR1-mut-nd
Time Frame: From first day of treatment until 6 months after first day of treatment
To determine the efficacy of elacestrant by 18F-FES-PET/CT result (homogeneous vs. heterogeneous) in participants with advanced/metastatic ER-positive breast cancer and ESR1-mut-nd.
From first day of treatment until 6 months after first day of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS) by central review as per (Response Evaluation Criteria In Solid Tumors) RECIST v1.143/ PET Response Criteria In Solid Tumours (PERCIST)
Time Frame: From the date of treatment initiation to the date of disease progression or death from any cause, up to the clinical data cut-off (approx. 2 years after the last participant has tarted treatment with elacestrant)
To determine the efficacy of elacestrant, PFS, by central review as per RECIST v1.143/ PERCIST39,44 by 18F-FES-PET/CT result.
From the date of treatment initiation to the date of disease progression or death from any cause, up to the clinical data cut-off (approx. 2 years after the last participant has tarted treatment with elacestrant)
Objective Response Rate (ORR) by central review, defined as per RECIST v1.143/ PERCIST
Time Frame: From the date of treatment initiation to the date of disease progression or death from any cause, up to the clinical data cut-off (approx. 2 years after the last participant has tarted treatment with elacestrant)
To evaluate the efficacy of elacestrant, by objective response rate (ORR), in the full analysis set and by 18F-FES-PET/CT result.
From the date of treatment initiation to the date of disease progression or death from any cause, up to the clinical data cut-off (approx. 2 years after the last participant has tarted treatment with elacestrant)
Overall Survival (OS), defined as time from the date of treatment start to the date of death from any cause.
Time Frame: From the date of treatment initiation to the date of disease progression or death from any cause, up to the clinical data cut-off (approx. 2 years after the last participant has tarted treatment with elacestrant)
To evaluate the efficacy of elacestrant, by OS, in the full analysis set and by 18F-FES PET/CT result.
From the date of treatment initiation to the date of disease progression or death from any cause, up to the clinical data cut-off (approx. 2 years after the last participant has tarted treatment with elacestrant)
PFS and OS rates at 6-month and at 12-month
Time Frame: From the date of treatment initiation to the date of disease progression or death from any cause, up to the clinical data cut-off (approx. 2 years after the last participant has tarted treatment with elacestrant)
To determine the efficacy of elacestrant by PFS and OS at landmark timepoints of 6stuyd-month and 12-month rate.
From the date of treatment initiation to the date of disease progression or death from any cause, up to the clinical data cut-off (approx. 2 years after the last participant has tarted treatment with elacestrant)
Time to subsequent chemotherapy, defined as time from the date of start of elacestrant to the date of subsequent chemotherapy start or cancer-related death, whichever comes first.
Time Frame: From the date of treatment initiation to the date of disease progression or death from any cause, up to the clinical data cut-off (approx. 2 years after the last participant has tarted treatment with elacestrant)
To evaluate the impact of 18F-FES-PET/CT homogeneity on time to subsequent chemotherapy.
From the date of treatment initiation to the date of disease progression or death from any cause, up to the clinical data cut-off (approx. 2 years after the last participant has tarted treatment with elacestrant)
Association between 18F-FES-PET/CT heterogeneity score and progression-free survival in participants treated with elacestrant.
Time Frame: From the date of treatment initiation to the date of disease progression or death from any cause, up to the clinical data cut-off (approx. 2 years after the last participant has tarted treatment with elacestrant)
To retrospectively find the optimal 18F-FES-PET/CT homogeneity threshold to demonstrate the superiority in PFS in participants treated with elacestrant.
From the date of treatment initiation to the date of disease progression or death from any cause, up to the clinical data cut-off (approx. 2 years after the last participant has tarted treatment with elacestrant)
Incidence, nature, and severity of adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events, version 6.0 (NCI CTCAE, v6.0).
Time Frame: From the date of treatment initiation to the date of disease progression or death from any cause, up to the clinical data cut-off (approx. 2 years after the last participant has tarted treatment with elacestrant)
To evaluate the safety and tolerability of elacestrant.
From the date of treatment initiation to the date of disease progression or death from any cause, up to the clinical data cut-off (approx. 2 years after the last participant has tarted treatment with elacestrant)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Exploratory objective: PFS in participants treated with elacestrant according to predefined 18F-FES-PET/CT heterogeneity threshold categories.
Time Frame: From the date of treatment initiation to the date of disease progression or death from any cause, up to the clinical data cut-off (approx. 2 years after the last participant has tarted treatment with elacestrant)
To assess PFS across predefined strata of 18F-FES-PET/CT heterogeneity threshold.
From the date of treatment initiation to the date of disease progression or death from any cause, up to the clinical data cut-off (approx. 2 years after the last participant has tarted treatment with elacestrant)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jules Bordet Institute

Collaborators

GE Healthcare
Menarini Group

Investigators

  • Study Chair: Martine Piccart, Md, PhD, Jules Bordet Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 13, 2026

Primary Completion (Estimated)

August 19, 2031

Study Completion (Estimated)

August 19, 2031

Study Registration Dates

First Submitted

April 17, 2026

First Submitted That Met QC Criteria

August 6, 2026

First Posted (Actual)

August 10, 2026

Study Record Updates

Last Update Posted (Actual)

August 10, 2026

Last Update Submitted That Met QC Criteria

August 6, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IJB-IRENA-2025
  • 2025-524380-20 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe