Breast Cancer
Conditions
Keywords
early-stage, HR+ breast cancer, breast cancer, premenopausal patients, stage I-II, ER+/HER2- breast cancer
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.
Interventions
DRUGElacestrant
Patients will receive elacestrant 345 mg/daily administered orally for 4 weeks.
DRUGLeuprorelin
Patients randomized in arm B will recieve Leuprorelin at Day 1 and Day 29
Sponsors
Menarini Group
Gustave Roussy, Cancer Campus, Grand Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Each patient must meet all of the following inclusion criteria to be randomized in the study: 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. 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 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 : 1. Absolute neutrophil count ≥ 1.0 x 109/L 2. Platelet count ≥ 75 x 109/L 3. Hemoglobin ≥ 9.0 g/dL 4. 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). 5. Alanine aminotransferase (ALT) ≤ 2.5x upper limit of normal (ULN). 6. Aspartate aminotransferase (AST) ≤ 3x ULN. 7. Total bilirubin ≤ ULN or total bilirubin ≤ 1.5x ULN with direct bilirubin ≤ ULN of the laboratory in subjects with documented Gilbert's Syndrome. 8. 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. 9. 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: 1. 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. 2. Placement of a non-hormonal intrauterine device.
Exclusion criteria
Patients who meet any of the following
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | From baseline to day 29 | partial and complete response obtained as measured by MRI |
| 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 | — |
| Complete cell cycle arrest (CCCA) measured by Ki67 <2.7% | Surgery | — |
| Incidence of treatment-emergent AEs | From enrollment until 28 days post surgery | assessed by the national cancer institute (NCI) Common Terminology for Classification of Adverse Events (CTCAE) version 5.0, |
| Duration of treatment-emergent AEs | From enrollment until 28 days post surgery | assessed by the national cancer institute (NCI) Common Terminology for Classification of Adverse Events (CTCAE) version 5.0, |
| Severity of treatment-emergent | From enrollment until 28 days post surgery | AEs assessed by the national cancer institute (NCI) Common Terminology for Classification of Adverse Events (CTCAE) version 5.0 |
| Levels of luteinizing hormone (LH) | at baseline, Day 14, and Day 28 then postoperatively at 1 month | — |
Countries
France
Contacts
Primary ContactElie El Rassy, MD
Backup ContactChloé Serhal, PhD
Outcome results
None listed