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

HER2-negative Breast Cancer Clinical Trial

— TREAT ctDNA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05512364
• Other study ID #: EORTC-2129-BCG
• Status: Recruiting
• Phase: Phase 3
• Start date: December 15, 2023
• Est. completion date: May 1, 2030

Study information

• Verified date: January 2024
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: EORTC HQ
• Phone: +32 2 774 16 11
• Email: eortc[@]eortc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 220
• Est. completion date: May 1, 2030
• Est. primary completion date: July 1, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• ER-positive Breast Cancer
• HER2-negative Breast Cancer
• Stage IIB Breast Cancer
• Stage III Breast Cancer

Intervention

Drug:
• Elacestrant
400mg QD orally on a continuous dosing schedule
• Tamoxifen
20 mg QD orally on a continuous dosing schedule
• Letrozole 2.5mg
2.5 mg QD orally on a continuous dosing schedule
• Anastrozole 1mg
1 mg QD orally on a continuous dosing schedule
• Exemestane 25 MG
25 mg QD orally on a continuous dosing schedule

Locations

Country	Name	City	State
Belgium	Institut Jules Bordet	Anderlecht
Belgium	AZ KLINA Brasschaat	Brasschaat
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	Grand Hopital de Charleroi - Site Notre Dame	Charleroi
Belgium	Pole Hospitalier Jolimont - Hopital Jolimont	Haine-Saint-Paul
Belgium	AZ Groeninge Kortrijk - Campus Kennedylaan	Kortrijk
Belgium	U.Z. Leuven - Campus Gasthuisberg	Leuven
Belgium	AZ Delta - Campus Menen	Menen
Belgium	CHU Site Sainte-Elisabeth-UCL Namur	Namur
Belgium	AZ Delta - Campus Rumbeke	Roeselare
Belgium	AZ Delta Torhout	Torhout
Belgium	AZ Turnhout - Campus Sint Elisabeth	Turnhout
Belgium	Centre Hospitalier Regional Verviers	Verviers
France	CH de La Cote Basque - Saint Leon	Bayonne
France	Centre de Radiotherapie Pierre Curie	Beuvry
France	Centre Hospitalier - Boulogne Sur Mer	Boulogne-sur-Mer
France	CHU de Lyon - Hopital Femme Mere Enfant	Bron
France	Centre d'Oncology Radiotherapie (ROC-37)	Chambray-lès-Tours
France	CHU de Lyon - Hopital De La Croix Rousse	Lyon
France	Centre d'Oncologie de Gentilly	Nancy
France	CHU de Lyon - Hopital Lyon Sud	Pierre-Bénite
France	Institut de Cancerologie Strasbourg Europe	Strasbourg
France	CHU de Toulouse - Institut Claudius Regaud - IUCT oncopole	Toulouse
Germany	MVM MbH -Onkologie UnterEms, Leer-Papenburg-Emden	Leer
Germany	Universitaetsklinikum Ulm-Michelsberg	Ulm
Germany	Helios Klinikum Wuppertal - Klin. Univ. Witten / Herdecke	Wuppertal
Ireland	Beacon Hospital	Dublin
Ireland	Mater Misericordia University Hospital	Dublin
Ireland	St James's Hospital	Dublin
Ireland	University Hospital Waterford	Waterford
Italy	Centro Di Riferimento Oncologico	Aviano
Italy	Azienda Ospedaliera Papa Giovanni XXIII	Bergamo
Italy	Azienda Ospedaliero-Universitaria Careggi	Firenze
Italy	Azienda USL IRCCS Di Reggio Emilia Guastalla	Guastalla
Italy	Ospedale Alessandro Manzoni	Lecco
Italy	Mater Salutis Hospital	Legnano
Italy	IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"	Meldola
Italy	Cliniche Humanitas Gavazzeni	Milano
Italy	Istituto Europeo di Oncologia	Milano
Italy	Istituti Clinici Scientifici Maugeri	Pavia
Italy	San Maria della Misericordia Hospital	Perugia
Italy	Azienda USL IRCCS Di Reggio Emilia - Maria Nuova	Reggio Emilia

Sponsors (3)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC	Breast International Group, Menarini Group

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Ireland,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Distant metastasis free survival (DMFS)	DMFS defined as the time from randomisation until first distant metastatic recurrence or death from any cause, whichever occurs first	5.2 years after first patient screened
Secondary	ctDNA elimination rate at month 1	defined as the proportion of randomised patients who had a negative ctDNA test result at month 1	at month 1