Detail Article

Informations générales (source: ClinicalTrials.gov)

Numéro NCT

NCT05512364 En recrutement IDF

Titre

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

Type

Interventional

Pathologie

Tumeurs du sein

Phase

Phase 3

Promoteur

European Organisation for Research and Treatment of Cancer - EORTC (Voir sur ClinicalTrials)

Date de début

décembre 2023

Date de fin

novembre 2035

Dernière mise à jour

02 septembre 2025

Résumé

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.

Détail

Voir le détail 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. Fermer le détail

Etablissements

Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données
CLCC INSTITUT CURIE		En recrutement IDF	10/04/2025 13:12:07	Contact (sur clinicalTrials)
CLCC RENE HUGUENIN INSTITUT CURIE		En recrutement IDF	10/04/2025 13:11:54	Contact (sur clinicalTrials)

Critères

Genre

Tous

Nombre d'inclusion

Critère d'inclusion

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 ≥ 5 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:

Critère de non inclusion

- 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 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

- 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

NCT05512364 - Elacestrant for Treating ER+/HER2- Breast Cancer Patients With ctDNA Relapse

Informations générales
Etablissements
Critères
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