Elacestrant for Treating ER+/HER2- Breast Cancer Patients With ctDNA Relapse (TREAT ctDNA)

NCT05512364 | Recruiting Phase 3 DMC

• 1 other identifier: EORTC-2129-BCG
• Study Type: interventional
• Target: 220
• Locations: 11 countries
• Sites: 94

Brief Summary

This is an international, multi-center, randomised, open label, superiority phase III trial of elacestrant vs standard endocrine therapy in patients with ER+/HER2- breast cancer and ctDNA relapse. During the ctDNA screening phase, patients will be tested at different timepoints to detect the presence of ctDNA in their blood. Patients who are found to be ctDNA-positive and have no evidence of distant metastasis, will be randomised 1:1 between standard endocrine treatment (the same they were receiving when tested ctDNA positive) versus elacestrant, provided they meet all eligibility criteria. After completion of the protocol treatment period, treatment will be left at the discretion of the treating physician.

Conditions

ER-positive Breast Cancer; HER2-negative Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Distant metastasis free survival (DMFS)

  Distant metastasis free survival (DMFS) defined as the time from randomisation until first distant metastatic recurrence or death from any cause, whichever occurs first

  Final DFMS will be 6.25 years after the first patient randomised.

Secondary Outcomes (7)

• Invasive disease-free survival (iDFS)

  Through study completion, up to 11.7 years

• Relapse-free survival (RFS)

  Through study completion, up to 11.7 years

• Overall survival rate

  Through study completion, up to 11.7 years

• Adverse events

  as of randomization until 30 days after administration of the last dose of protocol treatment.

• Health Related Quality of Life QLQ-C30

  weeks 4, 16, 32, 48, 64 and 80

Study Arms (2)

Experimental arm

EXPERIMENTAL

elacestrant 400 mg/day orally once daily on a continuous dosing schedule

Drug: Elacestrant

Control arm

ACTIVE COMPARATOR

standard endocrine treatment - the same they were receiving at the time of ctDNA detection

Drug: Tamoxifen; Drug: Letrozole 2.5mg; Drug: Anastrozole 1mg; Drug: Exemestane 25 MG

Interventions

Elacestrant DRUG

400mg QD orally on a continuous dosing schedule

Experimental arm

Tamoxifen DRUG

20 mg QD orally on a continuous dosing schedule

Control arm

Letrozole 2.5mg DRUG

2.5 mg QD orally on a continuous dosing schedule

Control arm

Anastrozole 1mg DRUG

1 mg QD orally on a continuous dosing schedule

Control arm

Exemestane 25 MG DRUG

25 mg QD orally on a continuous dosing schedule

Control arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ctDNA screening phase:
• Female (both pre- and postmenopausal) or male patients with histologically confirmed ER positive (regardless of PR),
• HER2 negative breast cancer, according to local pathologist:
• ER-positive defined as ≥ 10% of cells staining positive for ER or Allred proportion score ≥3
• HER2-negative defined as a score of 0, 1+ by immunohistochemistry (IHC) or a negative in situ hybridization (ISH) based on single-probe average HER2 copy number, as per American Society of Clinical Oncology guidelines
• Intermediate to high risk of recurrence after definitive treatment for early breast cancer, defined as:
• FOR PATIENTS TREATED WITH PRIMARY SURGERY:
• Any patient with ≥ 4 positive axillary lymph nodes (stage pN2-3).
• positive axillary lymph nodes (stage pN1) and either:
• Tumour size ≥ 5 cm or/and
• Histologic grade 3 or/and
• Ki67≥20% or/and
• High genomic risk defined as Oncotype Dx Recurrence Score \>=26, Mammaprint high risk, Prosigna score \>40 or EPclin risk score \>=4.0.
• Negative axillary lymph nodes (stage pN0) and tumour size ≥ 5 cm and either
• Histologic grade 3 a or/and

You may not qualify if:

• Prior treatment with any SERD or investigational ER antagonist
• Previous history of invasive breast cancer
• Previous history of any other malignancy within the last 5 years, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ.
• Previous history of bone marrow and/or organ transplant
• Bilateral breast cancer
• Participation in another clinical study, with the exception of the SURVIVE study and observational (non-interventional) and non-drug intervention clinical studies. Note: patients participating in interventional studies may participate once they enter the follow-up period of the study
• Blood transfusion within 3 months prior to registration or during the screening.
• Randomised trial:
• ctDNA positive according to the Signatera ctDNA assay (main study ctDNA test) or other ctDNA assay approved for diagnostic purposes.
• Patients must meet the eligibility criteria for the screening phase, with the exception of the tissue sample requirements.
• Patients must receive adjuvant ET at the time of the ctDNA positive test
• Absence of locoregional and/or metastatic disease and/or new malignancy, as investigated by:
• Mammogram (unilateral in case of mastectomy; not required in patients having undergone bilateral mastectomy) NOTE: if local investigator plans to use MRIs instead of mammograms during the study, MRI will have to be performed at baseline.
• CT thorax and abdomen/pelvis with IV contrast. In case of any contra-indications (medical or regulatory): CT thorax without contrast + MRI abdomen/pelvis.
• Technetium-99m bone scintigraphy

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• Breast International Group: collaborator
• Menarini Group: collaborator

Study Sites (94)

Institut Jules Bordet

Anderlecht, 1070, Belgium

RECRUITING

AZ KLINA

Brasschaat, 2930, Belgium

RECRUITING

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

RECRUITING

Grand Hopital de Charleroi - Site Notre Dame

Charleroi, 6000, Belgium

RECRUITING

CHU Helora Pole Hospitalier Jolimont - Hopital Jolimont

Haine-Saint-Paul, 7100, Belgium

RECRUITING

AZ Groeninge Kortrijk - Campus Kennedylaan

Kortrijk, 8500, Belgium

RECRUITING

U.Z. Leuven - Campus Gasthuisberg

Leuven, 3000, Belgium

RECRUITING

CHU Site Sainte-Elisabeth-UCL Namur

Namur, 5000, Belgium

RECRUITING

AZ Delta - Campus Rumbeke

Roeselare, 8800, Belgium

RECRUITING

AZ Turnhout - Campus Sint Elisabeth

Turnhout, 2300, Belgium

RECRUITING

Centre Hospitalier Regional Verviers

Verviers, 4800, Belgium

RECRUITING

German Oncology Center

Limassol, 4108, Cyprus

RECRUITING

Bank Of Cyprus Oncology Centre

Stróvolos, 2006, Cyprus

RECRUITING

CH de La Cote Basque - Saint Leon

Bayonne, 64100, France

RECRUITING

Clinique Belharra-Ramsay Sante

Bayonne, 64100, France

RECRUITING

Centre de Radiotherapie Pierre Curie

Beuvry, 62660, France

RECRUITING

Centre Hospitalier - Boulogne Sur Mer

Boulogne-sur-Mer, 62321, France

RECRUITING

CHU de Lyon - Hopital Femme Mere Enfant

Bron, 69677, France

RECRUITING

Societe de Recherche Oncologique Clinique 37

Chambray-lès-Tours, 31170, France

RECRUITING

Hopital de Douai- Centre Leonard de Vinci

Dechy, 59187, France

RECRUITING

CHU de Limoges - Hopital Dupuytren

Limoges, 87042, France

RECRUITING

CHU de Lyon - Hopital De La Croix Rousse

Lyon, 69004, France

RECRUITING

Polyclinique De Gentilly - Centre d'Oncologie

Nancy, 54100, France

RECRUITING

CHU de Lyon - Hopital Lyon Sud

Pierre-Bénite, 69495, France

RECRUITING

Institut Curie - l'Hopital de St Cloud

Saint-Cloud, 92210, France

RECRUITING

CHU de Toulouse - Institut Claudius Regaud - IUCT oncopole

Toulouse, 31059, France

RECRUITING

Universitaetsklinikum Aachen AOR - Medizinische Fakultaet der RWTH

Aachen, 52074, Germany

RECRUITING

Gemeinschaftspraxis Augsburg

Augsburg, 86150, Germany

RECRUITING

Evangelisches Krankenhaus -Bergisch Gladbach

Bergisch Gladbach, 51465, Germany

RECRUITING

Marienhospital Bottrop gGmbH

Bottrop, 46236, Germany

RECRUITING

Hamatologische Onkologische Praxis Im Medicum

Bremen, 28209, Germany

RECRUITING

St Elisabeth-Krankenhaus

Cologne, 50935, Germany

RECRUITING

Universitaetsklinikum Carl Gustav Carus (TUD)

Dresden, 01307, Germany

RECRUITING

Medizinische Hochschule Hannover

Hanover, 30625, Germany

RECRUITING

Gemeinschaftspraxis Dr. Pourfard / Dr. Uleer

Hildesheim, 31134, Germany

RECRUITING

Klinikum Kassel Gmbh

Kassel, 34125, Germany

RECRUITING

MVM MbH -Onkologie UnterEms, Leer-Papenburg-Emden

Leer, 26789, Germany

RECRUITING

Busch MCZ GmbH

Mühlhausen, 99974, Germany

RECRUITING

Klinikum Nuernberg- Standort Nord

Nuremberg, 90419, Germany

RECRUITING

Klinikum Ernst von Bergmann gemeinnützige GmbH

Potsdam, 14467, Germany

RECRUITING

Universitaetsklinikum Tuebingen-calwerstrasse

Tübingen, 72076, Germany

RECRUITING

Universitaetsklinikum Ulm-Michelsberg

Ulm, 89075, Germany

RECRUITING

HELIOS Kliniken - Helios Klinikum Wuppertal - Klin. Univ. Witten / Herdecke

Wuppertal, 42283, Germany

RECRUITING

Diagnostic & Therapeutic Center of Athens Hygeia Hospital S.A.

Athens, 15123, Greece

RECRUITING

General University Hospital of Larissa

Larissa, 41110, Greece

RECRUITING

Mater Private Hospital

Dublin, D07 WKW8, Ireland

RECRUITING

St. James'S Hospital

Dublin, D08 NHY1, Ireland

RECRUITING

Beacon Hospital

Dublin, D18 AK68, Ireland

RECRUITING

Centro Di Riferimento Oncologico

Aviano, 33081, Italy

RECRUITING

Azienda Ospedaliera Papa Giovanni XXIII

Bergamo, 24127, Italy

RECRUITING

Univ. of Florence -Azienda Ospedaliero-Universitaria Careggi

Florence, 50134, Italy

RECRUITING

IRCCS Azienda Policlinico San Martino

Genova, 16132, Italy

RECRUITING

Azienda USL IRCCS Di Reggio Emilia Guastalla

Guastalla, 42016, Italy

RECRUITING

Ospedale Alessandro Manzoni

Lecco, 23900, Italy

RECRUITING

Azienda Unita Locale Socio-Sanitaria N. 9-Mater Salutis Hospital

Legnano, 37045, Italy

RECRUITING

IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"

Meldola, 47014, Italy

RECRUITING

University Hospital of Cagliari Duilio Casula Hospital Unit (Policlinico)

Monserrato, 09042, Italy

RECRUITING

Azienda Ospedaliera Universitaria "Federico II"

Napoli, 80131, Italy

RECRUITING

Azienda Ospedaliero-Universitaria di Parma

Parma, 43126, Italy

RECRUITING

Istituti Clinici Scientifici Maugeri

Pavia, 27100, Italy

RECRUITING

San Maria della Misericordia Hospital

Perugia, 06129, Italy

RECRUITING

Azienda Ospedaliera Universitaria Pisana

Pisa, 56126, Italy

RECRUITING

Azienda USL IRCCS Di Reggio Emilia - Maria Nuova

Reggio Emilia, 42100, Italy

RECRUITING

AUSL Romagna - AUSL Della Romagna - Infermi Hospital -Rimini

Rimini, 47923, Italy

RECRUITING

Flevoziekenhuis Stichting

Almere Stad, 1315 RA, Netherlands

RECRUITING

Amsterdam UMC - locatie VUMC

Amsterdam, 1081 HV, Netherlands

RECRUITING

Rijnstate Hospital

Arnhem, 6815, Netherlands

RECRUITING

Haaglanden Medisch Centrum

Leidschendam, 2262 BA, Netherlands

RECRUITING

Ikazia Ziekenhuis

Rotterdam, 3083, Netherlands

RECRUITING

Sint Antonius - St Antonius Ziekenhuis Utrecht

Utrecht, 3543, Netherlands

RECRUITING

VieCuri - Medisch Centrum voor Noord-Limburg - Locatie Venlo

Venlo, 5912, Netherlands

RECRUITING

Hospital General Universitario Doctor Balmis

Alicante, 03010, Spain

RECRUITING

Hospital Universitario De Cruces

Barakaldo, 48903, Spain

RECRUITING

Hospital Clinico Universitario - Virgen De La Arrixaca

El Palmar, 30120, Spain

RECRUITING

ICO Girona - Hospital Doctor Josep Trueta

Girona, 17007, Spain

RECRUITING

Hospital Universitario Virgen De Las Nieves

Granada, 18014, Spain

RECRUITING

Hospital Universitario Clinico San Cecilio

Granada, 18016, Spain

RECRUITING

ICO L'Hospitalet - Hospital Duran i Reynals

L'Hospitalet de Llobregat, 08908, Spain

RECRUITING

Hospital Universitari Arnau De Vilanova

Lleida, 25196, Spain

RECRUITING

Hospital Universitario 12 De Octubre

Madrid, 28041, Spain

RECRUITING

Hospitales HM Sanchinarro-CIOCC

Madrid, 28050, Spain

RECRUITING

Althaia Xarxa Assistencial Universitaria De Manresa Fundacio Privada

Manresa, 08242, Spain

RECRUITING

Hospital Universitari Son Espases

Palma de Mallorca, 07010, Spain

RECRUITING

Hospital Universitario de Navarra

Pamplona, 31008, Spain

RECRUITING

Hospital Sant Joan de Reus

Reus, 43204, Spain

RECRUITING

Hospital Quironsalud Sagrado Corazon

Seville, 41013, Spain

RECRUITING

University Hospital Virgen del Rocio

Seville, 41013, Spain

RECRUITING

Hospital Universitario Virgen De La Macarena

Seville, 41071, Spain

RECRUITING

Hospital Clinico Universitario De Valencia

Valencia, 46010, Spain

RECRUITING

Hospital Universitario Y Politecnico La Fe

Valencia, 46026, Spain

RECRUITING

Sodra Alvsborgs Sjukhus - Vastra Gotalandsregionen

Borås, 50182, Sweden

RECRUITING

Karolinska University Hospital, location Solna

Stockholm, 17164, Sweden

RECRUITING

Kantonsspital Frauenfeld- Breast Unit Thurgau

Frauenfeld, 8500, Switzerland

RECRUITING

Buergerspital Solothurn -Brustzentrum

Solothurn, 4500, Switzerland

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

elacestrant; Tamoxifen; Letrozole; Anastrozole; exemestane

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Michail Ignatiadis

  Institut Jules Bordet, Belgium

  STUDY CHAIR

• Emmanouil Saloustros

  General University Hospital of Larissa, Greece

  STUDY CHAIR

Central Study Contacts

EORTC HQ

CONTACT

+32 2 774 16 11; eortc@eortc.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2022
• First Posted: August 23, 2022
• Study Start: December 15, 2023
• Primary Completion (Estimated): November 1, 2032
• Study Completion (Estimated): November 1, 2035
• Last Updated: August 19, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CY (2); SE (2); IE (3); FR (13); GR (2); IT (16); DE (17); NL (7); CH (2); BE (11); ES (19)