Status:
RECRUITING
Elacestrant for Treating ER+/HER2- Breast Cancer Patients With ctDNA Relapse (TREAT ctDNA)
Lead Sponsor:
European Organisation for Research and Treatment of Cancer - EORTC
Collaborating Sponsors:
Breast International Group
Menarini Group
Conditions:
ER-positive Breast Cancer
HER2-negative Breast Cancer
Eligibility:
All Genders
18+ years
Phase:
PHASE3
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. Du...
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 scre...
Eligibility Criteria
Inclusion
- 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.
Exclusion
- 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.
- 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
Key Trial Info
Start Date :
December 15 2023
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
November 1 2035
Estimated Enrollment :
220 Patients enrolled
Trial Details
Trial ID
NCT05512364
Start Date
December 15 2023
End Date
November 1 2035
Last Update
August 19 2025
Active Locations (94)
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1
Institut Jules Bordet
Anderlecht, Belgium, 1070
2
AZ KLINA
Brasschaat, Belgium, 2930
3
Cliniques Universitaires Saint-Luc
Brussels, Belgium, 1200
4
Grand Hopital de Charleroi - Site Notre Dame
Charleroi, Belgium, 6000