A Short-term Preoperative, 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

NCT07159451 | Recruiting Phase 2

• 2 other identifiers: 2024-520051-24-002025/4053
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

A prospective randomized trial designed to evaluate the mean decrease in Ki67 after 4 weeks of elacestrant monotherapy and in combination with leuprorelin in patients with early-stage HR+ BC. This preoperative study will enroll consecutive patients with early stage HR+ BC who are not candidates for neoadjuvant chemotherapy but are eligible for short-term preoperative treatment with elacestrant, with or without leuprorelin, followed by breast surgery. A total of three dedicated Formalin-fixed paraffin embedded (FFPE) samples (mandatory for all patients), along with two frozen biopsy (only for participants at Gustave Roussy), are planned to be collected at the time of inclusion from the biopsy sample and from the surgical specimen. Blood samples will also be collected throughout the study.

Conditions

Breast Cancer

Keywords

early-stage; HR+ breast cancer; breast cancer; premenopausal patients; stage I-II; ER+/HER2- breast cancer

Outcome Measures

Primary Outcomes (1)

• 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-positive/HER2- operable invasive BC.

  Surgery

Secondary Outcomes (9)

• Complete cell cycle arrest (CCCA) measured by Ki67 <2.7%

  Surgery

• Objective Response Rate

  From baseline to day 29

• Rate of pathological of partial and complete response

  at surgery

• Levels of estradiol

  at baseline, Day 14, and Day 28 then postoperatively at 1 month

• Levels of follicle-stimulating hormone (FSH)

  at baseline, Day 14, and Day 28 then postoperatively at 1 month

Study Arms (2)

Experimental group A

EXPERIMENTAL

Patients will receive elacestrant 345 mg/daily administered orally for 4 weeks.

Drug: Elacestrant

Experimental group B

EXPERIMENTAL

Patients will receive elacestrant 345 mg/daily administered orally for 4 weeks with leuprorelin LP 3.75 mg intramuscular Day 1 and Day 29.

Drug: Elacestrant; Drug: Leuprorelin

Interventions

Elacestrant DRUG

Patients will receive elacestrant 345 mg/daily administered orally for 4 weeks.

Experimental group A; Experimental group B

Leuprorelin DRUG

Patients randomized in arm B will recieve Leuprorelin at Day 1 and Day 29

Experimental group B

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 or more.
• 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.
• Patients must be affiliated to a Social Security System (or equivalent).
• 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.
• 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.
• Clinical stage I or II according to the eight edition of the American Joint Committee on Cancer, eligible for primary breast surgery.
• Note: Multifocal and multicentric tumors are permitted if they are considered clinical stage I or II according to Eight Edition of the AJCC. Biopsy of all lesions is not necessary and is left at the description of the investigator, but endocrine therapy response must be evaluated on the same tumor
• Available pre-treatment tru-cut biopsy evaluable.
• 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.
• Women of childbearing potential have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study medication.
• Absolute neutrophil count ≥ 1.0 x 109/L
• Platelet count ≥ 75 x 109/L
• Hemoglobin ≥ 9.0 g/dL
• 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).
• Alanine aminotransferase (ALT) ≤ 2.5x upper limit of normal (ULN).

You may not qualify if:

• Patients non-candidate for upfront breast surgery or candidate for neoadjuvant chemotherapy.
• Any systemic therapy (e.g, chemotherapy, targeted therapy, immune-therapy) or radiotherapy for current BC before study entry.
• Prior treatment with LHRH-agonists over the last 6 months prior to the ICF signature.
• Any active treatment for any cancer disease.
• Any of the following within 6 months before enrollment:
• Myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE v5.0 Grade ≥2,
• 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,
• Cerebrovascular accident including transient ischemic attack
• Child-Pugh Score greater than Class A,
• Has a known hypersensitivity (≥ Grade 3) to the components of the study therapy or its analogs.
• 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:
• Adequately treated catheter-related venous thrombosis occurring \> 28 days prior to the first dose of study drug
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead
• Menarini Group: collaborator

Study Sites (1)

Gustave Roussy

Villejuif, France

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

elacestrant; Leuprolide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Central Study Contacts

Elie El Rassy, MD

CONTACT

+33 01 42 11 42 11; Elie.EL-RASSY@gustaveroussy.fr

Chloé Serhal, PhD

CONTACT

+33 01 42 11 42 11; Chloe.serhal@gustaveroussy.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2025
• First Posted: September 8, 2025
• Study Start: October 6, 2025
• Primary Completion (Estimated): January 29, 2027
• Study Completion (Estimated): May 29, 2027
• Last Updated: December 1, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)