protocolSection identificationModule nctId: NCT06382948, orgStudyIdInfo id: MedOPP545, secondaryIdInfos id: 2024-512926-27-00, type: CTIS, briefTitle: Elacestrant + Everolimus in Patients ER+/HER2-, ESR1mut, Advanced Breast Cancer Progressing to ET and CDK4/6i., acronym: ADELA, statusModule overallStatus: NOT_YET_RECRUITING, startDateStruct date: 2024-06, primaryCompletionDateStruct date: 2027-09, completionDateStruct date: 2028-04, studyFirstPostDateStruct date: 2024-04-24, lastUpdatePostDateStruct date: 2024-04-26, sponsorCollaboratorsModule leadSponsor name: MedSIR, class: OTHER, collaborators name: Stemline Therapeutics, Inc., descriptionModule briefSummary: 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., conditionsModule conditions: Advanced Breast Cancer, conditions: ER-positive Breast Cancer, conditions: HER2-negative Breast Cancer, conditions: ESR1 Gene Mutation, designModule studyType: INTERVENTIONAL, phases: PHASE3, designInfo allocation: RANDOMIZED, interventionModel: PARALLEL, interventionModelDescription: Double-blind, parallel group (two arms: elacestrant plus everolimus, and elacestrant plus placebo)., primaryPurpose: TREATMENT, maskingInfo masking: DOUBLE, maskingDescription: 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., whoMasked: PARTICIPANT, whoMasked: INVESTIGATOR, enrollmentInfo count: 240, type: ESTIMATED, armsInterventionsModule interventions name: Everolimus, interventions name: Elacestrant, interventions name: Placebo, interventions name: Auxiliary Medicinal Product - Dexamethasone, interventions name: Auxiliary Medicinal Product - Luteinizing hormone-releasing hormone (LHRH) analogues, outcomesModule primaryOutcomes measure: 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)., secondaryOutcomes measure: To compare overall survival (OS) between treatment groups, in all patients., secondaryOutcomes measure: To compare investigator-assessed PFS based on local assessment between treatment groups, in all patients., secondaryOutcomes measure: To compare objective response rate (ORR) between treatment groups, in all patients., secondaryOutcomes measure: To compare clinical benefit rate (CBR) between treatment groups, in all patients., secondaryOutcomes measure: To compare overall time to response (TTR) between treatment groups, in all patients., secondaryOutcomes measure: To compare duration of response (DoR) between treatment groups, in all patients., secondaryOutcomes measure: To compare best percentage of change in tumor burden between treatment groups, in all patients., secondaryOutcomes measure: To describe the changes in health-related quality-of-life (HRQoL) from baseline using the EuroQoL 5 Dimension 5 Level (EQ-5D-5L) scale., secondaryOutcomes measure: To describe the changes in HRQoL from baseline using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)., secondaryOutcomes measure: To describe the changes in HRQoL from baseline using the EORTC Quality of Life Questionnaire Breast Cancer module (EORTC QLQ-BR45)., secondaryOutcomes measure: To assess adverse events (AEs) between treatment groups in all patients., secondaryOutcomes measure: To assess adverse events leading to study treatment withdrawal., secondaryOutcomes measure: To assess adverse events leading to dose modification., secondaryOutcomes measure: To assess the number of participants with abnormal hematology and/or chemistry values that are related to treatment., secondaryOutcomes measure: To assess the number of participants with changes on vital signs and/or AEs that are related to treatment., secondaryOutcomes measure: To assess the number of participants with changes on cardiac function measured by ECG QT Interval Corrected by Fridericia formula (QTcF) that are related to treatment effect ., secondaryOutcomes measure: To assess the number of participants with changes on Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) that are related to treatment., otherOutcomes measure: Exploratory endpoint: protein expression studies using blood samples to investigate the potential association with clinical outcomes., otherOutcomes measure: Exploratory endpoint: analysis of allele mutation frequencies in circulating tumor DNA (ctDNA) in blood samples to investigate the potential association with clinical outcomes., otherOutcomes measure: Exploratory endpoint: Genetic studies using blood samples to investigate the potential association with clinical outcomes., otherOutcomes measure: Exploratory endpoint: Analysis of medical imaging (radiomics) to identify potential biomarkers associated with clinical outcomes., otherOutcomes measure: Exploratory endpoint: Pharmacokinetic (PK) parameter of maximum (Peak) Observed Serum Concentration (Cmax)., otherOutcomes measure: Exploratory endpoint: Pharmacokinetic (PK) parameter of Plasma Through Concentration (Ctrough)., eligibilityModule sex: ALL, minimumAge: 18 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule, hasResults: False