A short-term preoperative, window-of-opportunity study, evaluating activity and safety of Elacestrant monotherapy as compared to Elacestrant + ovarian function suppression (LHRH agonist) in premenopausal patients with stage I-II ER+/HER2- breast cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut Gustave Roussy

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

30 Sep 2025 → ongoing

Decision date (initial)

2025-08-18

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Menarini (BERLIN CHEMIE AG)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

To determine if 4 weeks of elacestrant monotherapy determines a non-inferior anti-proliferative effect, measured by Ki67, in comparison to elacestrant with leuprorelin in premenopausal patients with ER+/HER2- stage I/II invasive breast cancer.

Secondary objectives 2

1. To compare the clinical and biological downstaging obtained by elacestrant monotherapy versus elacestrant with leuprorelin in premenopausal women
2. To assess the safety and tolerability of elacestrant as single agent or in combination with leuprorelin in premenopausal women

Conditions and MedDRA coding

Breast cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Aged 18 or more
2. Signed Informed Consent Form prior to any study-specific procedure. Patients must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures.
3. Patients must be affiliated to a Social Security System (or equivalent).
4. Premenopausal women ensured by checking if the women were still having regular periods over the last 6 months without any hormonal treatment or hormonal contraception or if they were irregular, FSH and estradiol levels must fall within the premenopausal range according to local laboratory definition.
5. Histologically confirmed invasive breast carcinoma, confirmed by the local pathologist, ER-positive tumor cells ≥ 10% ER staining BC and HER2- according to ASCO criteria in immunohistochemistry (IHC) and/or genomic analysis (HER2 negativity is defined as IHC 0-1+, or [IHC 2+ and in situ hybridization non-amplified]), Ki67 index by local analysis of ≥ 10% and ≤ 30% on untreated tumor tissue.
6. Clinical stage I or II according to the eight edition of the American Joint Committee on Cancer, eligible for primary breast surgery.
7. Available pre-treatment tru-cut biopsy evaluable.
8. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 14 days prior to the date of randomization.
9. Women of childbearing potential have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study medication.
10. Demonstrate adequate organ function within 7 days of inclusion : a. Absolute neutrophil count ≥ 1.0 x 109/L b. Platelet count ≥ 75 x 109/L c. Hemoglobin ≥ 9.0 g/dL d. Estimated glomerular filtration rate ≥30 mL/min/1.73 m² or creatinine clearance calculated by Cockcroft-Gault equation ≥ 30 mL/min Creatinine clearance ≥ 30 mL/min for subject with creatinine levels > 1.5 x institutional upper limit of normal (ULN). e. Alanine aminotransferase (ALT) ≤ 2.5x upper limit of normal (ULN). f. Aspartate aminotransferase (AST) ≤ 3x ULN. g. Total bilirubin ≤ ULN or total bilirubin ≤ 1.5x ULN with direct bilirubin ≤ ULN of the laboratory in subjects with documented Gilbert’s Syndrome. h. Potassium, sodium, calcium (corrected for albumin), magnesium, and phosphorus CTCAE v5.0 Grade ≤ 1. If Screening assessments are abnormal, chemistry assessments may be repeated up to 2 times; subjects may receive appropriate supplementation or treatment (eg, for hypercalcemia) prior to re-assessment. i. International normalized ratio (INR) ≤ 1.5; subjects who are receiving anticoagulation treatment which is monitored by international normalized ratio (INR) (eg, warfarin) may be allowed to participate if they have a stable INR (ie, within therapeutic range) for at least 28 days prior to the first dose of study drug, in the absence of any exclusionary medical conditions, and provided that elacestrant would be appropriate therapy for the subject.
11. Women of childbearing potential must agree to use protocol-specified method(s) of contraception during trial treatments and for at least 120 days after the last dose of trial treatments. Highly effective contraception methods include: a. Total abstinence (when this is in line with the preferred and usual lifestyle of the patient). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. b. Placement of a non-hormonal intrauterine device.

Exclusion criteria 14

1. Participants non-candidate for upfront breast surgery or candidate for neoadjuvant chemotherapy.
2. Any concurrent severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with compliance with study procedures or the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study.
3. Person deprived of their liberty or under protective custody or guardianship.
4. Psychological, familial, sociological or geographical conditions that do not permit compliance with the study protocol.
5. Patients unwilling to or unable (as assessed by the investigator) to comply with the protocol.
6. Any systemic therapy (e.g, chemotherapy, targeted therapy, immune-therapy) or radiotherapy for current BC before study entry.
7. Prior treatment with LHRH-agonists over the last 6 months prior to the ICF signature.
8. Any active treatment for any cancer disease
9. Any of the following within 6 months before enrollment: a. Myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE v5.0 Grade ≥2, b. Prolonged QTcF ≥ Grade 2 (ie, > 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, c. Cerebrovascular accident including transient ischemic attack d. Child-Pugh Score greater than Class A, e. Has a known hypersensitivity (≥ Grade 3) to the components of the study therapy or its analogs. f. Coagulopathy or any history of coagulopathy within the past 6 months, including history of deep vein thrombosis or pulmonary embolism. However, subjects with the following conditions will be allowed to participate: g. Adequately treated catheter-related venous thrombosis occurring > 28 days prior to the first dose of study drug
10. Treatment with an anticoagulant, eg, warfarin or heparin, for a thrombotic event occurring > 6 months before enrollmentenrolment, or for an otherwise stable and allowed medical condition (eg, 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 (ie, 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 (eg, St. John’s wort), and/or foods (eg, grapefruit, pomelos, star fruit, Seville oranges and their juices) that are moderate/strong inhibitors or inducers of CYP3A4 activity. 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 study entry and for the duration of the study.
13. Pregnancy or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes.
14. Participation in another clinical study with an investigational product during the last 4 weeks prior to enrollment and while on study treatment and until 6 months after the end of study treatment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in Ki67 (the percentage of immunostaining cells).

Secondary endpoints 2

1. Evaluation of clinical and biological response in the 2 arms by:  Complete cell cycle arrest as measured by Ki67 <2.7%  Clinical response (partial or complete) as measured by MRI  Rate of pathological partial and complete response at surgery  Changes in the levels of estradiol, FSH, and LH between baseline, D14, and D28, then postoperatively at 1 month.
2. Incidence, duration, and severity of treatment-emergent Adverse Events (AEs) assessed by the NCI Common Terminology for Classification of Adverse Events (CTCAE) version 5.0, including dose delays and treatment discontinuations. Incidence of ovarian cyst occurrence up to 6 months after surgery, assessed by CTCAE version 5.0

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut Gustave Roussy

Sponsor organisation

Institut Gustave Roussy

Address

114 Rue Edouard Vaillant

City

Villejuif

Postcode

94800

Country

France

Scientific contact point

Organisation

Institut Gustave Roussy

Contact name

Bureau projet Promotion- DRC-Regulatory Affairs Officer

Public contact point

Organisation

Institut Gustave Roussy

Contact name

Bureau projet Promotion- DRC-Regulatory Affairs Officer

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications