NCT06382948

Elacestrant + Everolimus in Patients ER+/HER2-, ESR1mut, Advanced Breast Cancer Progressing to ET and CDK4/6i.

A Randomized Phase 3, Double-Blind, Placebo-Controlled Study of Elacestrant Plus Everolimus Versus Elacestrant in Patients With ER+/HER2-, ESR1mut Advanced Breast Cancer Progressing to Endocrine Therapy and CDK4/6 Inhibitors

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 240 (estimated)
• Sponsor: MedSIR · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This trial will study a type of advanced breast cancer (ABC) defined as endocrine receptor (ER)-positive/human epidermal growth factor receptor 2(HER2)-negative and estrogen receptor 1 (ESR1)-mutated. Patients will be treated with elacestrant, a compound that acts as a selective estrogen receptor degrader, and everolimus (or placebo), a kinase inhibitor indicated for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer. The main purpose of the study is to analyze the efficacy (to find out how effective a treatment is) of elacestrant plus everolimus therapy in patients who have ER-positive/HER2-negative, ESR1-mutated, ABC progressing to endocrine therapy and cyclin-dependent kinase 4/6 (CDK4/6) inhibitor. The efficacy of elacestrant plus everolimus combination will be determined by assessing the period from elacestrant plus everolimus (or placebo) treatment initiation until to the first occurrence of disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason, whichever occurs first, defined as progression free survival. Rigorous eligibility criteria based on specific co-morbidities and clinicopathologic features of their disease have been designed to minimize the risk of patients participating in this study. The anticipated favorable clinical benefits of elacestrant combined with everolimus are projected to outweigh the risks of this treatment. This study will be performed in full compliance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and all applicable local Good Clinical Practice (GCP) and regulations.

Detailed description

Upon meeting all selection criteria, a total of 240 patients will be enrolled. After signing the Informed Consent Form (ICF), patients will be randomized (ratio 1:1) as follows: * Interventional Arm (Arm A) (N=120): Patients will receive 345 mg of elacestrant and 7.5 mg of everolimus orally once daily. * Control Arm (Arm B) (N=120): Patients will receive elacestrant at 345 mg orally once daily plus everolimus placebo. Patients will be stratified by presence of visceral metastases (yes versus no) and duration of prior CDK4/6 inhibitor-based therapy (≥ 12 months versus \< 12 months). Patients progressing to CDK4/6 inhibitor-based therapy in the adjuvant setting will be stratified as patients with a duration of prior CDK4/6 inhibitor-based therapy \< 12 months. Patients will receive study treatment in 28-day cycles until documented disease progression, death, unacceptable toxicity, or discontinuation from the study treatment for any other reason, whichever occurs first. Patients discontinuing the study treatment period will enter a post-treatment follow-up period during which survival and new anti-cancer therapy information will be collected every 3 months (± 14 days) from the last dose of IMPs until the End of Study (EoS) defined as 12 months after last patient is randomized unless premature termination of the trial. For patients who discontinue the study treatment for reasons other than disease progression, tumor assessments will be conducted following the frequency of the study until the start of a new anti-cancer treatment, death, or disease progression.

Conditions

• Advanced Breast Cancer
• ER-positive Breast Cancer
• HER2-negative Breast Cancer
• ESR1 Gene Mutation

Interventions

Type	Name	Description
DRUG	Everolimus	Patients will receive 7.5 mg of everolimus orally once daily.
DRUG	Elacestrant	Patients will receive elacestrant 345 mg orally once daily
DRUG	Placebo	Patients will receive placebo orally once daily
DRUG	Auxiliary Medicinal Product - Dexamethasone	10 mL of alcohol-free dexamethasone 0.5 mg per 5 mL mouthwashes (swish for 2 min and spit, four times daily for 8 weeks). After 8 weeks, dexamethasone mouthwash could be continued for up to eight additional weeks at the discretion of the clinician and patient. Used for prevention of treatment-induced stomatitis.
DRUG	Auxiliary Medicinal Product - Luteinizing hormone-releasing hormone (LHRH) analogues	According to clinical practice (for premenopausal/perimenopausal patients and male patients in both treatment arms). Used to suppress estrogen production.

Timeline

• Start date: 2024-12-05
• Primary completion: 2027-09-01
• Completion: 2028-04-01
• First posted: 2024-04-24
• Last updated: 2026-04-03

Locations

99 sites across 9 countries: Austria, Brazil, Czechia, France, Germany, Greece, Italy, Spain, United Kingdom