ELACESTRANT DIHYDROCHLORIDE for Breast cancer

Inclusion criteria

• {"criterion_text":"- Aged 18 or more\n- 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.\n- 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.\n- 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.\n- Patients must be affiliated to a Social Security System (or equivalent).\n- 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.\n- 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.\n- Clinical stage I or II according to the eight edition of the American Joint Committee on Cancer, eligible for primary breast surgery.\n- Available pre-treatment tru-cut biopsy evaluable.\n- 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.\n- Women of childbearing potential have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study medication."}

Exclusion criteria

• {"criterion_text":"- Participants non-candidate for upfront breast surgery or candidate for neoadjuvant chemotherapy.\n- 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.\n- 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.\n- 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.\n- 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.\n- 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\n- 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.\n- Person deprived of their liberty or under protective custody or guardianship.\n- Psychological, familial, sociological or geographical conditions that do not permit compliance with the study protocol.\n- Patients unwilling to or unable (as assessed by the investigator) to comply with the protocol.\n- Any systemic therapy (e.g, chemotherapy, targeted therapy, immune-therapy) or radiotherapy for current BC before study entry.\n- Prior treatment with LHRH-agonists over the last 6 months prior to the ICF signature.\n- Any active treatment for any cancer disease\n- 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"}

Primary endpoints

• {"endpoint_text":"- Change from baseline in Ki67 (the percentage of immunostaining cells).","definition_or_measurement_approach":"Measured as change from baseline in Ki67 percentage by immunostaining of tumor tissue. The main objective further specifies evaluation by the proportion of Ki67 expression < 10% after surgery."}

Secondary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Includes assessment of complete cell cycle arrest defined as Ki67 <2.7%; clinical response assessed by MRI (partial or complete); pathological partial and complete response rate at surgery; and serial hormone measurements (estradiol, FSH, LH) at baseline, Day 14, Day 28 and 1 month postoperatively."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Safety assessed by incidence, duration and severity of treatment-emergent AEs using NCI CTCAE v5.0, including recording dose delays and discontinuations; ovarian cyst occurrence measured up to 6 months after surgery per CTCAE v5.0."}

France

Earliest CTIS Part Ii Submission Date

30-06-2025

Latest Decision Or Authorization Date

18-08-2025

Processing Time Days

49

Number Of Sites

5

Number Of Participants

140

Primary sponsor

Full Name

Institut Gustave Roussy

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"Menarini (BERLIN CHEMIE AG)","duties_or_roles":"Source of monetary support","organisation_type":""}