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

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.

Conditions

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

Interventions

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.

Sponsors & Collaborators

• Stemline Therapeutics, Inc.

  collaborator INDUSTRY

• MedSIR

  lead OTHER

Principal Investigators

• Javier Cortés, M.D., Ph.D. · IOB Institute of Oncology, Quironsalud Group, Madrid & Barcelona, Spain

• Antonio Llombart-Cussac, M.D., Ph.D. · Arnau de Vilanova Hospital, Valencia, Spain

• José Pérez-García, M.D., Ph.D. · International Breast Cancer Center, Barcelona, Spain

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-12-05

Primary Completion

2027-09-30

Completion

2028-04-30

Countries

• Austria
• Brazil
• Czechia
• France
• Germany
• Greece
• Italy
• Spain
• United Kingdom

Study Locations