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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Stage IIB Breast Cancer; ER-positive Breast Cancer; HER2-negative Breast Cancer; Stage III Breast Cancer
• Intervention / Treatment: Drug: Elacestrant; Drug: Tamoxifen; Drug: Letrozole 2.5mg; Drug: Anastrozole 1mg; Drug: Exemestane 25 MG

Detailed Description

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.

1. ctDNA screening phase: After verification of the eligibility criteria for screening, patients will enter the ctDNA screening phase of the study in which plasma samples will be collected and tested with ctDNA assay to detect the presence of ctDNA. The test will be performed every 6 months from study entry until the end of accrual (approximately 5.7 years). During the screening phase, patients will be treated with standard adjuvant endocrine therapy [either tamoxifen or an aromatase inhibitor (exemestane, anastrozole or letrozole)] and followed-up as per standard of care. The outcome of the serial ctDNA assessments performed during the screening phase will be disclosed to investigators.

   Patients who are found to be ctDNA-negative at the end of the screening period will not be followed further in this study.

   Patients who are found to be ctDNA-positive at one of the screening time points will undergo an imaging work-up to assess the presence of distant metastases.

   Patients for whom the imaging work-up confirms no evidence of distant metastases or locoregional recurrence will be eligible for the randomised phase of the study provided they meet all other eligibility criteria. Patients for whom the imaging work-up shows evidence of distant metastases or locoregional recurrence will be excluded.

2. Randomised trial:

Patients will be randomised 1:1 within 4 weeks from the date of ctDNA detection (i.e., the date on which the results of the test are received) between standard endocrine treatment (the same they were receiving when tested ctDNA positive) versus elacestrant.

In the absence of a withdrawal criteria, treatment in both arms will be administered for:

• For patients on ET between 1 to 5 years (12 to 60 months) at the time of randomisation: 2 to 6 years (allowing for 7 years of ET at the end of the study treatment).
• For patients on ET between 5 to 7.5 years (60 to 90 months) at the time of randomisation: 2 years.

After completion of the protocol treatment period, treatment will be left at the discretion of the treating physician.

Patients in both arms will undergo intensive follow-up with ctDNA tests at week 4 and week 16 after randomisation and every 16 weeks thereafter for a maximum of 3 years (36 months or 156 weeks) to assess ctDNA kinetics. In addition, the occurrence of distant metastases, locoregional recurrences and second cancers will be assessed via yearly mammograms and bone scans and 16-weekly CT scans thorax/abdomen for a maximum of 3 years after randomisation. Afterwards, follow-up will continue as per standard of care. All randomised patients will be followed-up until 3 years after the enrolment of the last patient.

End of study:

End of study occurs when all the following criteria have been satisfied:

All patients have completed their end of study visit. If a patient discontinues the follow-up due to withdrawal of consent, loss to follow-up, or death, the end of study participation is defined as the time point when one of these events occurred The trial is mature for all analyses defined in the protocol and the database has been cleaned and frozen for these analyses.

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: EORTC HQ; Phone Number: +32 2 774 16 11; Email: eortc@eortc.org

Study Locations

• Belgium
  • Anderlecht, Belgium, 1070
    • Recruiting
    • Institut Jules Bordet
  • Brussels, Belgium, 1200
    • Recruiting
    • Cliniques Universitaires Saint-Luc
  • Brussels, Belgium
    • Recruiting
    • Hopital Universitaire Brugmann
  • Charleroi, Belgium, 6000
    • Recruiting
    • Grand Hôpital de Charleroi - Site Notre Dame
  • Haine-Saint-Paul, Belgium, 7100
    • Recruiting
    • CHU Helora Pole Hospitalier Jolimont - Hopital Jolimont
  • Kortrijk, Belgium, 8500
    • Recruiting
    • AZ Groeninge Kortrijk - Campus Kennedylaan
  • Leuven, Belgium, 3000
    • Recruiting
    • U.Z. Leuven - Campus Gasthuisberg
  • Namur, Belgium, 5000
    • Recruiting
    • CHU Site Sainte-Elisabeth-UCL Namur
  • Roeselare, Belgium, 8800
    • Recruiting
    • AZ Delta - Campus Rumbeke
  • Verviers, Belgium, 4800
    • Recruiting
    • Centre Hospitalier Regional Verviers
• Cyprus
  • Limassol, Cyprus, 4108
    • Recruiting
    • German Oncology Center
  • Stróvolos, Cyprus, 2006
    • Recruiting
    • Bank Of Cyprus Oncology Centre
• France
  • Bayonne, France, 64100
    • Recruiting
    • Clinique Belharra-Ramsay Sante
  • Beuvry, France, 62660
    • Recruiting
    • Centre de Radiotherapie Pierre Curie
  • Boulogne-sur-Mer, France, 62321
    • Recruiting
    • Centre Hospitalier - Boulogne Sur Mer
  • Bron, France, 69677
    • Recruiting
    • CHU de Lyon - Hôpital Femme Mère Enfant
  • Chambray-lès-Tours, France, 31170
    • Recruiting
    • Societe de Recherche Oncologique Clinique 37
  • Dechy, France, 59187
    • Recruiting
    • Hopital de Douai- Centre Leonard de Vinci
  • Limoges, France, 87042
    • Recruiting
    • CHU de Limoges - Hôpital Dupuytren
  • Lyon, France, 69004
    • Recruiting
    • CHU de Lyon - Hopital de la Croix Rousse
  • Lyon, France
    • Recruiting
    • CHU de Lyon - Hopital de la Croix Rousse
  • Nancy, France, 54100
    • Recruiting
    • Polyclinique De Gentilly - Centre d'Oncologie
  • Paris, France
    • Recruiting
    • Institut Curie - Hôpital de Paris
  • Pierre-Bénite, France, 69495
    • Recruiting
    • CHU de Lyon - Hopital Lyon Sud
  • Pierre-Bénite, France
    • Recruiting
    • CHU de Lyon - Hopital Lyon Sud
  • Saint-Cloud, France, 92210
    • Recruiting
    • Institut Curie - l'Hopital de St Cloud
  • Toulouse, France, 31059
    • Recruiting
    • CHU de Toulouse - Institut Claudius Regaud - IUCT oncopole
• Germany
  • Aachen, Germany, 52074
    • Recruiting
    • Universitaetsklinikum Aachen AOR - Medizinische Fakultaet der RWTH
  • Augsburg, Germany, 86150
    • Recruiting
    • Gemeinschaftspraxis Augsburg
  • Bergisch Gladbach, Germany, 51465
    • Recruiting
    • Evangelisches Krankenhaus -Bergisch Gladbach
  • Bottrop, Germany, 46236
    • Recruiting
    • Marienhospital Bottrop gGmbH
  • Bremen, Germany, 28209
    • Recruiting
    • Hamatologische Onkologische Praxis Im Medicum
  • Cologne, Germany, 50935
    • Recruiting
    • St Elisabeth-Krankenhaus
  • Dresden, Germany, 01307
    • Recruiting
    • Universitaetsklinikum Carl Gustav Carus (TUD)
  • Hanover, Germany, 30625
    • Recruiting
    • Medizinische Hochschule Hannover
  • Hildesheim, Germany, 31134
    • Recruiting
    • Gemeinschaftspraxis Dr. Pourfard / Dr. Uleer
  • Kassel, Germany, 34125
    • Recruiting
    • Klinikum Kassel Gmbh
  • Leer, Germany, 26789
    • Recruiting
    • MVM MbH -Onkologie UnterEms, Leer-Papenburg-Emden
  • Mühlhausen, Germany, 99974
    • Recruiting
    • Busch MCZ GmbH
  • München, Germany
    • Recruiting
    • Klinikum rechts der Isar München
  • Nuremberg, Germany, 90419
    • Recruiting
    • Klinikum Nuernberg- Standort Nord
  • Potsdam, Germany, 14467
    • Recruiting
    • Klinikum Ernst von Bergmann gemeinnützige GmbH
  • Rheine, Germany
    • Recruiting
    • Mathias Spital Rheine
  • Tübingen, Germany, 72076
    • Recruiting
    • Universitaetsklinikum Tuebingen-calwerstrasse
  • Ulm, Germany, 89075
    • Recruiting
    • Universitaetsklinikum Ulm-Michelsberg
  • Weinheim, Germany
    • Recruiting
    • GRN Klinik Weinheim
  • Winnenden, Germany
    • Recruiting
    • Rems-Murr-Kliniken gGmbH
  • Wuppertal, Germany, 42283
    • Recruiting
    • HELIOS Kliniken - Helios Klinikum Wuppertal - Klin. Univ. Witten / Herdecke
• Greece
  • Athens, Greece, 15123
    • Recruiting
    • Diagnostic & Therapeutic Center of Athens Hygeia Hospital S.A.
  • Larissa, Greece, 41110
    • Recruiting
    • General University Hospital Of Larissa
  • Thessaloniki, Greece
    • Recruiting
    • Agios Loukas Clinic (St Lukes)
• Ireland
  • Dublin, Ireland, D07 WKW8
    • Recruiting
    • Mater Private Hospital
  • Dublin, Ireland, D18 AK68
    • Recruiting
    • Beacon Hospital
  • Dublin, Ireland, D08 NHY1
    • Recruiting
    • St. James's Hospital
  • Dublin, Ireland
    • Recruiting
    • Mater Misericordia University Hospital
  • Waterford, Ireland
    • Recruiting
    • University Hospital Waterford
• Italy
  • Aviano, Italy, 33081
    • Recruiting
    • Centro di Riferimento Oncologico
  • Bergamo, Italy, 24127
    • Recruiting
    • Azienda Ospedaliera Papa Giovanni XXIII
  • Florence, Italy, 50134
    • Recruiting
    • Univ. of Florence -Azienda Ospedaliero-Universitaria Careggi
  • Genova, Italy, 16132
    • Recruiting
    • IRCCS Azienda Policlinico San Martino
  • Guastalla, Italy, 42016
    • Recruiting
    • Azienda USL IRCCS Di Reggio Emilia Guastalla
  • Lecco, Italy, 23900
    • Recruiting
    • Ospedale Alessandro Manzoni
  • Legnano, Italy, 37045
    • Recruiting
    • Azienda Unita Locale Socio-Sanitaria N. 9-Mater Salutis Hospital
  • Meldola, Italy, 47014
    • Recruiting
    • IRCCS Istituto Romagnolo per lo Studio Dei Tumori (IRST) "Dino Amadori"
  • Milan, Italy
    • Recruiting
    • Instituto Europeo di Oncologia
  • Modena, Italy
    • Recruiting
    • Azienda Ospedaliero - Universitaria Policlinico di Modena
  • Monserrato, Italy, 09042
    • Recruiting
    • University Hospital of Cagliari Duilio Casula Hospital Unit (Policlinico)
  • Naples, Italy, 80131
    • Recruiting
    • Azienda Ospedaliera Universitaria "Federico II"
  • Parma, Italy, 43126
    • Recruiting
    • Azienda Ospedaliero-Universitaria di Parma
  • Pavia, Italy, 27100
    • Recruiting
    • Istituti Clinici Scientifici Maugeri
  • Perugia, Italy, 06129
    • Recruiting
    • San Maria della Misericordia Hospital
  • Peschiera del Garda, Italy
    • Recruiting
    • Ospedale P. Pederzoli Casa di cura Privata
  • Pisa, Italy, 56126
    • Recruiting
    • Azienda Ospedaliera Universitaria Pisana
  • Reggio Emilia, Italy, 42100
    • Recruiting
    • Azienda USL IRCCS Di Reggio Emilia - Maria Nuova
  • Rimini, Italy, 47923
    • Recruiting
    • AUSL Romagna - AUSL Della Romagna - Infermi Hospital -Rimini
• Netherlands
  • Almere Stad, Netherlands, 1315 RA
    • Recruiting
    • Flevoziekenhuis Stichting
  • Amsterdam, Netherlands, 1081 HV
    • Recruiting
    • Amsterdam UMC - Locatie VUmc
  • Arnhem, Netherlands, 6815
    • Recruiting
    • Rijnstate Hospital
  • Leidschendam, Netherlands, 2262 BA
    • Recruiting
    • Haaglanden Medisch Centrum
  • Rotterdam, Netherlands, 3083
    • Recruiting
    • Ikazia Ziekenhuis
  • Utrecht, Netherlands, 3543
    • Recruiting
    • Sint Antonius - St Antonius Ziekenhuis Utrecht
  • Venlo, Netherlands, 5912
    • Recruiting
    • VieCuri - Medisch Centrum voor Noord-Limburg - Locatie Venlo
• Portugal
  • Lisbon, Portugal
    • Recruiting
    • Hospital CUF Tejo
  • Vila Nova de Gaia, Portugal
    • Recruiting
    • Centro Hospitalar Vila Nova Gaia/Espinho
• Spain
  • Alicante, Spain, 03010
    • Recruiting
    • Hospital General Universitario Doctor Balmis
  • Barakaldo, Spain, 48903
    • Recruiting
    • Hospital Universitario de Cruces
  • El Palmar, Spain, 30120
    • Recruiting
    • Hospital Clinico Universitario - Virgen De La Arrixaca
  • Girona, Spain, 17007
    • Recruiting
    • ICO Girona - Hospital Doctor Josep Trueta
  • Granada, Spain, 18014
    • Recruiting
    • Hospital Universitario Virgen de Las Nieves
  • Granada, Spain, 18016
    • Recruiting
    • Hospital Universitario Clínico San Cecilio
  • L'Hospitalet de Llobregat, Spain, 08908
    • Recruiting
    • ICO l'Hospitalet - Hospital Duran i Reynals
  • Lleida, Spain, 25196
    • Recruiting
    • Hospital Universitari Arnau de Vilanova
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain, 28050
    • Recruiting
    • Hospitales HM Sanchinarro-CIOCC
  • Manresa, Spain, 08242
    • Recruiting
    • Althaia Xarxa Assistencial Universitaria De Manresa Fundacio Privada
  • Palma de Mallorca, Spain, 07010
    • Recruiting
    • Hospital Universitari Son Espases
  • Pamplona, Spain, 31008
    • Recruiting
    • Hospital Universitario de Navarra
  • Reus, Spain, 43204
    • Recruiting
    • Hospital Sant Joan de Reus
  • Seville, Spain, 41013
    • Recruiting
    • University Hospital Virgen del Rocio
  • Seville, Spain, 41013
    • Recruiting
    • Hospital Quironsalud Sagrado Corazón
  • Seville, Spain, 41071
    • Recruiting
    • Hospital Universitario Virgen De La Macarena
  • Valencia, Spain, 46010
    • Recruiting
    • Hospital Clinico Universitario de Valencia
  • Valencia, Spain, 46026
    • Recruiting
    • Hospital Universitario y Politécnico La Fe
• Sweden
  • Borås, Sweden, 50182
    • Recruiting
    • Sodra Alvsborgs Sjukhus - Vastra Gotalandsregionen
  • Lund, Sweden
    • Recruiting
    • Skåne University Hospital
  • Stockholm, Sweden, 17164
    • Recruiting
    • Karolinska University Hospital, location Solna
• Switzerland
  • Frauenfeld, Switzerland, 8500
    • Recruiting
    • Kantonsspital Frauenfeld- Breast Unit Thurgau
  • Solothurn, Switzerland, 4500
    • Recruiting
    • Buergerspital Solothurn -Brustzentrum

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. ctDNA screening phase:

   Main inclusion criteria:

   • 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).
   • 1-3 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 ≥ 2 cm and either
   • Histologic grade 3 a or/and
   • Ki67≥20% and/or
   • High genomic risk defined as Oncotype Dx Recurrence Score >=26, Mammaprint high risk, Prosigna score >60 or EPclin risk score >=4.0. FOR PATIENTS TREATED WITH NEOADJUVANT

   SYSTEMIC TREATMENT FOLLOWED BY SURGERY:

   • Patient may have received neoadjuvant endocrine therapy or neoadjuvant chemotherapy provided that:
   • The initial tumour and/or the tumour after surgery meet the criteria above defined for patients treated with primary surgery or the initial tumour was staged as cT4anyN and
   • There is no pathological complete response, defined as no invasive disease in the breast and axilla (ypT0/is ypN0).
   • Age ≥18 years
   • Patients must have received at least 1 year and up to 7.5 years of ET and planned to continue adjuvant ET during ctDNA screening phase
   • Previous adjuvant CDK4/6 inhibitor or PARP-inhibitor treatment is allowed provided it is completed
   • Invasive multicentric / multifocal disease is allowed provided that all the tested foci are ER+ HER2-. A sample from the highest-risk one, according to the investigator decision based on the size and grade, should be sent to Natera to build the patient ctDNA assay.
   • Available tumour sample from resected or biopsied tissue, with a tumour content of ≥20% (30% preferred) either before or after macro dissection (if performed) and a cell viability of a minimum 100 cells.
   • Core Needle Biopsies (CNB): recommended minimum of four (4) cores per block
   • Fine Needle Aspirates (FNA) are not accepted
   • The following sample types are acceptable:
   • 6-10 unstained slides (charged and unbaked) of 10μm each (or 12-19 unstained slides at 5 μm each), PLUS one contiguous H&E slide. Minimum total tissue thickness must be 60μm OR
   • FFPE tissue block with 25mm2 minimum surface area
   • Written informed consent must be given according to ICH/GCP, and national/local regulations.

   Main exclusion criteria:

   • Suspected recurrent disease or known conflicts with the inclusion and exclusion criteria for the randomised trial
   • 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 invasive 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.
2. Randomised trial:

Main inclusion criteria:

• 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
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
• Adequate organ function
• Women of childbearing potential (WOCBP) must have a negative highly sensitive serum or urine pregnancy test within 7 days prior to randomisation.

Main exclusion criteria:

• Any unresolved toxic effect of prior therapies or surgical procedures of Grade ≥ 2 according to Common Terminology Criteria of Adverse Events (CTCAE) v5.0, with the exception of alopecia, peripheral neuropathy and other toxicities not considered a safety risk for the participant at investigator's discretion
• Unable or unwilling to avoid over-the-counter medications, dietary/herbal supplements, and/or foods that are moderate/strong inhibitors or inducers of CYP3A4 activity
• Known difficulty in tolerating oral medications or conditions which would impair absorption of oral medications
• Any of the following cardiovascular disorders within 3 months before enrolment:
• myocardial infarction
• stroke
• severe/unstable angina
• symptomatic cardiac arrhythmia
• prolonged QTcF ≥ Grade 3 (i.e., > 500 msec)
• heart failure ≥ Class III as defined by the New York Heart Association (NYHA) guidelines
• CTCAE version 5.0 grade 3 or 4 dyslipidemia at the time of screening, defined as cholesterol>400 mg/dL or >10.34 mmol/L and/or triglycerides>500 mg/dL or >5.7 mmol/L.
• Child-Pugh Score greater than Class A
• Uncontrolled significant active infections (≥ grade 3 according to CTCAE version 5), including active hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency Virus (HIV)
• Coagulopathy or any history of coagulopathy within the past 6 months, including history of deep vein thrombosis or pulmonary embolism

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental arm; elacestrant 400 mg/day orally once daily on a continuous dosing schedule	Drug: Elacestrant; 400mg QD orally on a continuous dosing schedule
Active Comparator: Control arm; standard endocrine treatment - the same they were receiving at the time of ctDNA detection	Drug: Tamoxifen; 20 mg QD orally on a continuous dosing schedule; Drug: Letrozole 2.5mg; 2.5 mg QD orally on a continuous dosing schedule; Drug: Anastrozole 1mg; 1 mg QD orally on a continuous dosing schedule; Drug: Exemestane 25 MG; 25 mg QD orally on a continuous dosing schedule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Invasive disease-free survival (iDFS)	According to the STEEP criteria, it's defined as the time between the date of randomisation and the date of the first occurrence of one of the following events: loco-regional disease recurrence, distant metastasis, invasive contralateral breast cancer, invasive non-breast second cancer, or date of death from any cause	Through study completion, up to 11.7 years
Relapse-free survival (RFS)	Relapse-free survival (RFS) rate according to the STEEP criteria, including locoregional recurrence, distant metastasis, deaths from any cause as events	Through study completion, up to 11.7 years
Overall survival rate	Overall survival rate • Safety including but not limited to all adverse events, serious adverse events, laboratory abnormalities graded according to CTCAE version 5.0	Through study completion, up to 11.7 years
Adverse events	Safety including but not limited to all adverse events, serious adverse events, laboratory abnormalities graded according to CTCAE version 5.0	as of randomization until 30 days after administration of the last dose of protocol treatment.
Health Related Quality of Life QLQ-C30	European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30). This is a patient-reported questionnaire composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. All of the scales and single-item measures range in score from 0 to 100.A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems. Assessments will be performed at 21 days before randomisation, 4 weeks, 16 weeks, 32 weeks, 48 weeks, 64 weeks, and 80 weeks after randomisation using the following measures: QLQ-C30	weeks 4, 16, 32, 48, 64 and 80
Health Related Quality of Life EORTC IL146	Health-related quality of life (HRQoL) is a secondary endpoint in this trial. HRQoL assessment aims at; establishing the patient-reported tolerability profile in each treatment arm.; comparing the patient-reported benefit between the two treatment arms. Assessments will be performed at 21 days before randomisation, 4 weeks, 16 weeks, 32 weeks, 48 weeks, 64 weeks, and 80 weeks after randomisation using the following measures: EORTC IL146.	weeks 4, 16, 32, 48, 64 and 80
Health Related Quality of Life QLQ-BR42	Health-related quality of life (HRQoL) is a secondary endpoint in this trial. HRQoL assessment aims at; establishing the patient-reported tolerability profile in each treatment arm.; comparing the patient-reported benefit between the two treatment arms. Assessments will be performed at 21 days before randomisation, 4 weeks, 16 weeks, 32 weeks, 48 weeks, 64 weeks, and 80 weeksafter randomisation using the following measures:QLQ-BR42	weeks 4, 16, 32, 48, 64 and 80

Collaborators and Investigators

• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Collaborators: Hellenic Oncology Research Group; Natera, Inc.; Hellenic Cooperative Oncology Group; ETOP IBCSG Partners Foundation; SOLTI Breast Cancer Research Group; Menarini Group; Borstkanker Onderzoek Groep; Swedish Breast Cancer Group; Cancer Trials Ireland; SUCCESS
• Investigators: Study Chair: Michail Ignatiadis, Institut Jules Bordet, Belgium; Study Chair: Emmanouil Saloustros, General University Hospital of Larissa, Greece

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2023
• Primary Completion (Estimated): November 1, 2032
• Study Completion (Estimated): November 1, 2035

Study Registration Dates

• First Submitted: August 22, 2022
• First Submitted That Met QC Criteria: August 22, 2022
• First Posted (Actual): August 23, 2022

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Benzene Derivatives; Nitriles; Triazoles; Stilbenes; Benzylidene Compounds; Letrozole; Anastrozole; Tamoxifen; exemestane; elacestrant
• Other Study ID Numbers: EORTC-2129-BCG

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No