Clinical trial NCT05512364: Elacestrant for Treating ER+/HER2- Breast Cancer Patients With ctDNA Relapse (TREAT ctDNA)
Official title: Elacestrant for Treating ER+/HER2- Breast Cancer Patients With ctDNA Relapse
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: ER-positive Breast Cancer
HER2-negative Breast Cancer
Stage IIB Breast Cancer
Stage III Breast Cancer
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
Collaborators: name: Breast International Group
name: Menarini Group
First posted: 2022-08-23
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* ctDNA screening phase

  * Female 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
    * 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
  * Elevated risk of recurrence after definitive treatment for early breast cancer, defined as either:

    * Stage IIB or stage III disease according to the 8th edition of the UICC TNM classification and completion of adjuvant chemotherapy, OR
    * Completion of at least 4 cycles of neoadjuvant chemotherapy and residual tumour at surgery of ≥ 1cm (≥ypT1c) or axillary node + (ypN+)
  * Pre- or postmenopausal status (for female patients).
  * Age ≥18 years
  * Patients must have received at least 2 years and up to 7 years of ET
  * Previous adjuvant CDK4/6 inhibitor or PARP-inhibitor treatment is allowed if completed at least 12 months before registration
  * Patients with multifocal tumours are allowed provided all foci are biopsied and are ER-positive and HER2-negative as defined above
  * Available FFPE tumour block from the baseline biopsy or from surgical specimen or at least 10 slides of 10μm and a tumour cellularity of at least 25%. For patients with multifocal tumours, FFPE block or slides from the largest focus is required.
  * Written informed consent must be given according to ICH/GCP, and national/local regulations.
* Randomised phase

  * ctDNA positive according to the Signatera ctDNA assay
  * Absence of locoregional and/or metastatic disease, as investigated by:

    * Mammogram (unilateral in case of mastectomy; not required in patients having undergone bilateral mastectomy)
    * 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 3 days prior to randomisation.

Exclusion Criteria:

* ctDNA screening phase

  * 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 of the cervix . Patients who have been disease free for more than 5 years with low risk of relapse are allowed
  * Bilateral breast cancer
  * Participation in another clinical study, with the exception of the SURVIVE study Note: patients participating in interventional studies may participate once they enter the follow-up period of the study
* Randomised phase

  * 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 prescription medications, 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:
  * 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

Primary outcomes:
measure: Distant metastasis free survival (DMFS)
timeFrame: 5.2 years after first patient screened
Secondary outcomes:
measure: ctDNA elimination rate at month 1
timeFrame: at month 1
Other outcomes:
Locations:
city: Anderlecht
country: Belgium
facility: Institut Jules Bordet
city: Brasschaat
country: Belgium
facility: AZ KLINA Brasschaat
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Charleroi
country: Belgium
facility: Grand Hopital de Charleroi - Site Notre Dame
city: Haine-Saint-Paul
country: Belgium
facility: Pole Hospitalier Jolimont - Hopital Jolimont
city: Kortrijk
country: Belgium
facility: AZ Groeninge Kortrijk - Campus Kennedylaan
city: Leuven
country: Belgium
facility: U.Z. Leuven - Campus Gasthuisberg
city: Menen
country: Belgium
facility: AZ Delta - Campus Menen
city: Namur
country: Belgium
facility: CHU Site Sainte-Elisabeth-UCL Namur
city: Roeselare
country: Belgium
facility: AZ Delta - Campus Rumbeke
city: Torhout
country: Belgium
facility: AZ Delta Torhout
city: Turnhout
country: Belgium
facility: AZ Turnhout - Campus Sint Elisabeth
city: Verviers
country: Belgium
facility: Centre Hospitalier Regional Verviers
city: Bayonne
country: France
facility: CH de La Cote Basque - Saint Leon
city: Beuvry
country: France
facility: Centre de Radiotherapie Pierre Curie
city: Boulogne-sur-Mer
country: France
facility: Centre Hospitalier - Boulogne Sur Mer
city: Bron
country: France
facility: CHU de Lyon - Hopital Femme Mere Enfant
city: Chambray-lès-Tours
country: France
facility: Centre d'Oncology Radiotherapie (ROC-37)
city: Lyon
country: France
facility: CHU de Lyon - Hopital De La Croix Rousse
city: Nancy
country: France
facility: Centre d'Oncologie de Gentilly
city: Pierre-Bénite
country: France
facility: CHU de Lyon - Hopital Lyon Sud
city: Strasbourg
country: France
facility: Institut de Cancerologie Strasbourg Europe
city: Toulouse
country: France
facility: CHU de Toulouse - Institut Claudius Regaud - IUCT oncopole
city: Leer
country: Germany
facility: MVM MbH -Onkologie UnterEms, Leer-Papenburg-Emden
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm-Michelsberg
city: Wuppertal
country: Germany
facility: Helios Klinikum Wuppertal - Klin. Univ. Witten / Herdecke
city: Dublin
country: Ireland
facility: Beacon Hospital
city: Dublin
country: Ireland
facility: Mater Misericordia University Hospital
city: Dublin
country: Ireland
facility: St James's Hospital
city: Waterford
country: Ireland
facility: University Hospital Waterford
city: Aviano
country: Italy
facility: Centro Di Riferimento Oncologico
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Papa Giovanni XXIII
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi
city: Guastalla
country: Italy
facility: Azienda USL IRCCS Di Reggio Emilia Guastalla
city: Lecco
country: Italy
facility: Ospedale Alessandro Manzoni
city: Legnano
country: Italy
facility: Mater Salutis Hospital
city: Meldola
country: Italy
facility: IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"
city: Milano
country: Italy
facility: Cliniche Humanitas Gavazzeni
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Pavia
country: Italy
facility: Istituti Clinici Scientifici Maugeri
city: Perugia
country: Italy
facility: San Maria della Misericordia Hospital
city: Reggio Emilia
country: Italy
facility: Azienda USL IRCCS Di Reggio Emilia - Maria Nuova
Study officials:
affiliation: Institut Jules Bordet, Belgium
name: Michail Ignatiadis
role: STUDY_CHAIR
affiliation: General University Hospital of Larissa, Greece
name: Emmanouil Saloustros
role: STUDY_CHAIR
References: