Elacestrant + Everolimus in Patients ER+/HER2-, ESR1mut, Advanced Breast Cancer Progressing to ET and CDK4/6i.
ADELA
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
2 other identifiers
interventional
240
8 countries
69
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Dec 2024
Typical duration for phase_3
69 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 5, 2024
CompletedFirst Posted
Study publicly available on registry
April 24, 2024
CompletedStudy Start
First participant enrolled
December 5, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 1, 2028
March 12, 2026
December 1, 2025
2.7 years
April 5, 2024
March 11, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
To demonstrate superiority of elacestrant+everolimus vs. elacestrant+placebo in prolonging PFS based on a BIRC in patients with ER[+]/HER2[-], ESR1-mutated, ABC that have previously received ET+CDK4/6i (all patients).
Progression Free Survival (PFS), defined as the period from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first, as assessed by a Blinded Imaging Review Committee (BIRC) through the use of RECIST v.1.1.
Until disease progression, treatment discontinuation, the start of new anti-cancer treatment, withdrawal of consent, death, or EoS, whichever occurs first, assessed through study completion, an average of 12 months.
Secondary Outcomes (17)
To compare overall survival (OS) between treatment groups, in all patients.
Until disease progression, treatment discontinuation, the start of new anti-cancer treatment, withdrawal of consent, death, or EoS, whichever occurs first, assessed through study completion, an average of 12 months.
To compare investigator-assessed PFS based on local assessment between treatment groups, in all patients.
Until disease progression, treatment discontinuation, the start of new anti-cancer treatment, withdrawal of consent, death, or EoS, whichever occurs first, assessed through study completion, an average of 12 months.
To compare objective response rate (ORR) between treatment groups, in all patients.
Until disease progression, treatment discontinuation, the start of new anti-cancer treatment, withdrawal of consent, death, or EoS, whichever occurs first, assessed through study completion, an average of 12 months.
To compare clinical benefit rate (CBR) between treatment groups, in all patients.
Until disease progression, treatment discontinuation, the start of new anti-cancer treatment, withdrawal of consent, death, or EoS, whichever occurs first, assessed through study completion, an average of 12 months.
To compare overall time to response (TTR) between treatment groups, in all patients.
Until disease progression, treatment discontinuation, the start of new anti-cancer treatment, withdrawal of consent, death, or EoS, whichever occurs first, assessed through study completion, an average of 12 months.
- +12 more secondary outcomes
Other Outcomes (6)
Exploratory endpoint: protein expression studies using blood samples to investigate the potential association with clinical outcomes.
Until disease progression, treatment discontinuation, the start of new anti-cancer treatment, withdrawal of consent, death, or EoS, whichever occurs first, assessed through study completion, an average of 12 months.
Exploratory endpoint: analysis of allele mutation frequencies in circulating tumor DNA (ctDNA) in blood samples to investigate the potential association with clinical outcomes.
Until disease progression, treatment discontinuation, the start of new anti-cancer treatment, withdrawal of consent, death, or EoS, whichever occurs first, assessed through study completion, an average of 12 months.
Exploratory endpoint: Genetic studies using blood samples to investigate the potential association with clinical outcomes.
Until disease progression, treatment discontinuation, the start of new anti-cancer treatment, withdrawal of consent, death, or EoS, whichever occurs first, assessed through study completion, an average of 12 months.
- +3 more other outcomes
Study Arms (2)
Interventional Arm 1
EXPERIMENTALPatients will receive 345 mg of elacestrant and 7.5 mg of everolimus orally once daily. Patients will remain in treatment until disease progression, treatment discontinuation, the start of new anti-cancer treatment, withdrawal of consent, death, or EoS, whichever occurs first.
Control Arm 2
ACTIVE COMPARATORPatients will receive elacestrant at (345 mg orally once daily) plus matched everolimus placebo. Patients will remain in treatment until disease progression, treatment discontinuation, the start of new anti-cancer treatment, withdrawal of consent, death, or EoS, whichever occurs first.
Interventions
According to clinical practice (for premenopausal/perimenopausal patients and male patients in both treatment arms). Used to suppress estrogen production.
Patients will receive 7.5 mg of everolimus orally once daily.
Patients will receive elacestrant 345 mg orally once daily
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.
Eligibility Criteria
You may qualify if:
- Patients will be included in the study only if they meet ALL of the following criteria:
- Patient must be capable to understand the purpose of the study and have signed written informed consent form (ICF) prior to beginning specific protocol procedures.
- Female or male patients ≥ 18 years of age at the time of signing ICF.
- Pre- or perimenopausal women, who do not meet the criteria for post-menopausal status (defined in continuation) and men must be concurrently receiving a LHRH analogue for at least 28 days (if shorter, post-menopausal levels of serum estradiol/follicle-stimulating hormone \[FSH\] must be confirmed analytically) prior to study randomization and are planning to continue LHRH agonist treatment during the study.
- Post-menopausal women as defined by any of the following criteria:
- Age ≥ 60 years;
- Age \< 60 years and cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and serum estradiol and/or FSH levels within the laboratory's reference range for post-menopausal females;
- Documented bilateral surgical oophorectomy.
- Histologically- or cytologically proven diagnosis of adenocarcinoma of the breast with evidence of either unresectable locally recurrent or metastatic disease confirmed by computerized tomography (CT) scan or magnetic resonance imaging (MRI) that is not amenable to resection with curative intent.
- Documentation of ER\[+\] (≥10% positive stained cells) and HER2\[-\] (0-1+ by immunohistochemistry \[IHC\] or 2+ and negative by in situ hybridization \[ISH\] test) tumor according to the most recent American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines as per local assessment. ER\[+\]/HER2\[-\] status should be confirmed in metastatic setting, with exception of patients with bone and lung only disease.
- Patients with ESR1 mutational status will be determined before patient randomization using Guardant360 CDx (Guardant Health) test.
- Radiological or objective evidence of disease progression on prior treatment with a CDK4/6 inhibitor in combination with endocrine therapy for advanced disease after at least 6 months of treatment. Patients receiving CDK4/6 inhibitor-based therapy in the adjuvant setting are also eligible provided that disease progression is confirmed after at least 12 months of treatment but no more than 12 months following CDK4/6 inhibitor treatment completion in this scenario.
- Patients must have previously received at least one and no more than two lines of endocrine therapy for ABC. Progression during or within 12 months of adjuvant endocrine therapy is considered as a line of endocrine therapy for advanced disease.
- No prior elacestrant or other investigational SERDs, proteolysis targeting chimera (PROTAC), complete estrogen receptor antagonist (CERAN), or novel SERM, and/or PI3K/AKT/mTOR inhibitors, including everolimus, for advanced disease are permitted.
- Note: Fulvestrant is permitted if treatment was completed administered at least 28 days before randomization.
- +8 more criteria
You may not qualify if:
- Resolution of all acute toxic effects of prior anti-cancer therapy to grade ≤ 1 as determined by the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) v.5.0 (except for toxicities not considered a safety risk for the patient at Investigator's discretion).
- Note: Patients with grade 2 alopecia are allowed.
- Women of childbearing potential who are sexually active with a non-sterilized male partner must have a negative serum pregnancy test within 7 days before randomization. In addition, they agree to use one highly effective method of birth control 28 days prior to start of treatment until 120 days after the last dose of study treatments. Female patients must refrain from egg cell donation and breastfeeding during this same time period.
- Male participants with a female partner of childbearing potential must be surgically sterile or using a highly effective method of contraception 28 days prior to treatment until 120 days after the last dose of study treatments to prevent pregnancy in a partner. Male participants must not donate or bank sperm during this same time period. Not engaging in heterosexual activity (sexual abstinence) for the duration of the study and 120 days after the last dose of study treatments is an acceptable practice if this is the preferred usual lifestyle of the participant.
- ECOG performance status of 0-1.
- Minimum life expectancy of ≥ 12 weeks at screening.
- Any patient meeting ANY of the following criteria will be excluded from the study:
- Inability to comply with study and follow-up procedures.
- Formal contraindication to endocrine therapy defined as visceral crisis and/or rapidly or symptomatic progressive visceral disease.
- Current participation in another therapeutic clinical trial.
- Treatment with approved or investigational cancer therapy within 14 days prior to randomization except for fulvestrant that must be administered completed at least 28 days before randomization.
- Known active uncontrolled or symptomatic central nervous system (CNS) metastases and/or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS metastases are eligible if they have been previously treated with local therapy, are clinically stable, and off anticonvulsants and steroids for at least 14 days before randomization.
- Intact uterus with a history of endometrial intraepithelial neoplasia (atypical endometrial hyperplasia or higher-grade lesion).
- Concurrent malignancy or malignancy within three years before randomization with the exception of carcinoma in situ of the cervix, non-melanoma skin carcinoma, or stage I uterine cancer. For other cancers considered to have a low risk of recurrence, discussion with the Medical Monitor is required.
- Known allergy or hypersensitivity reaction to any investigational medicinal products (IMPs) or their incorporated substances.
- +20 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- MedSIRlead
- Stemline Therapeutics, Inc.collaborator
Study Sites (69)
Medizinische Universität Innsbruck
Innsbruck, Austria
Ordensklinikum Linz Barmherzige Schwestern
Linz, Austria
Ordination Priv.-Doz. Dr. Michael Hubalek
Schwaz, Austria
Masaryk Memorial Cancer Institute
Brno, Czechia
Multiscan Nemocnice Horovice
Hořovice, Czechia
Tomas Bata Regional Hospital in Zlin
Zlín, Czechia
Polyclinique Bordeaux Nord Aquitaine
Bordeau, France
Centre Georges François Leclerc
Dijon, France
CHU Lyon Sud
Lyon, France
Hospital prive des Cotes d'Amor
Plérin, France
CHU Saint Etienne
Saint-Priest-en-Jarez, France
IUCT Oncopole
Toulouse, France
Institute de Cancerologie de Lorraine - Nancy
Vandœuvre-lès-Nancy, France
MVZ II der Niels Stensen Kliniken
Georgsmarienhütte, Germany
Klinikum Worms - Frauenklinik
Worms, Germany
University General Hospital Alexandroupoli
Alexandroupoli, Greece
251 Air Force General Hospital
Athens, Greece
Aretaeio Hospital
Athens, Greece
Attikon University Hospital
Athens, Greece
Metropolitan General Hospital 4th department
Athens, Greece
University General Hospital of Heraklion
Heraklion, Greece
University General Hospital of Larissa
Larissa, Greece
Metropolitan Hospital Greece 1st department
Piraeus, Greece
EU Interbalkan Medical Center
Thessaloniki, Greece
Ospedali Riuniti Livorno
Livorno, Italy
Instituto Europeo di Oncologia
Milan, Italy
Azienda Ospedaliero- Universitaria Maggiore Della Carita
Novara, Italy
Hospital Universitari Dexeus
Barcelona, Barcelona, Spain
Centro Oncológico de Galicia
A Coruña, Spain
Complejo Hospitalario Universitario de Santiago (CHUS)
A Coruña, Spain
Hospital General Universitario Dr. Balmis (Alicante)
Alicante, Spain
Hospital Universitario San Juan de Alicante
Alicante, Spain
Institut Català d' Oncologia Badalona (ICO)
Badalona, Spain
Hospital Clínic i Provincial de Barcelona
Barcelona, Spain
Hospital del Mar
Barcelona, Spain
Hospital Universitari Vall D'Hebron
Barcelona, Spain
Hospital Universitario de Basurto
Bilbao, Spain
Hospital Universitario de Burgos
Burgos, Spain
Hospital Provincial de Castellón
Castellon, Spain
Hospital San Pedro de Alcántara
Cáceres, Spain
Hospital Universitario Clínico San Cecilio de Granada
Granada, Spain
Complejo Hospitalario de Jaén
Jaén, Spain
Hospital Universitario Insular de Gran Canaria
Las Palmas de Gran Canaria, Spain
Hospital Universitario de León
León, Spain
Hospital Universitario Arnau de Vilanova de Lleida
Lleida, Spain
Hospital Beata María Ana
Madrid, Spain
Hospital Universitario Doce de Octubre
Madrid, Spain
Hospital Universitario La Paz
Madrid, Spain
Hospital Universitario Puerta de Hierro Majadahonda
Madrid, Spain
Hospital Universitario Ramón y Cajal
Madrid, Spain
Hospital Universitario Sanchinarro-START-CIOCC
Madrid, Spain
MD Anderson Cancer Center Madrid
Madrid, Spain
Hospital Clínico Universitario Virgen de la Arrixaca
Murcia, Spain
Hospital Universitari Son Espases
Palma de Mallorca, Spain
Hospitalario Universitario de Navarra
Pamplona, Spain
Hospital Universitario de Canarias
Santa Cruz de Tenerife, Spain
Hospital Quirónsalud Sagrado Corazón
Seville, Spain
Hospital Universitario Virgen del Rocío
Seville, Spain
Hospital Universitario Virgen Macarena
Seville, Spain
Hospital Universitari Sant Joan de Reus
Tarragona, Spain
Hospital Universitario Marqués de Valdecilla
Valdecilla, Spain
Consorci Hospital General Universitari de València
Valencia, Spain
Hospital Arnau de Vilanova de Valencia
Valencia, Spain
Hospital Clínico Universitario de Valencia
Valencia, Spain
Hospital Universitario La Ribera - Alzira
Valencia, Spain
Hospital Clínico Universitario Lozano Blesa
Zaragoza, Spain
Barts Health NHS Trust
London, United Kingdom
Royal Cornwall Hospital NHS Trust
Truro, United Kingdom
Genesis Cancer Care UK
Waterlooville, United Kingdom
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Javier Cortés, M.D., Ph.D.
IOB Institute of Oncology, Quironsalud Group, Madrid & Barcelona, Spain
- PRINCIPAL INVESTIGATOR
Antonio Llombart-Cussac, M.D., Ph.D.
Arnau de Vilanova Hospital, Valencia, Spain
- PRINCIPAL INVESTIGATOR
José Pérez-García, M.D., Ph.D.
International Breast Cancer Center, Barcelona, Spain
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Masking Details
- A blinded, independent IRC will perform a review of radiographic images and clinical information collected on study to determine the protocol-defined endpoints of disease response and progression. Further information on the independent review process will be provided in the BIRC Charter.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 5, 2024
First Posted
April 24, 2024
Study Start
December 5, 2024
Primary Completion (Estimated)
September 1, 2027
Study Completion (Estimated)
April 1, 2028
Last Updated
March 12, 2026
Record last verified: 2025-12