NCT05512364

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

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

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 220 (estimated)
• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC · Network
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

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.

Conditions

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

Interventions

Type	Name	Description
DRUG	Elacestrant	400mg QD orally on a continuous dosing schedule
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

Timeline

• Start date: 2023-12-15
• Primary completion: 2032-11-01
• Completion: 2035-11-01
• First posted: 2022-08-23
• Last updated: 2025-08-19

Locations

94 sites across 11 countries: Belgium, Cyprus, France, Germany, Greece, Ireland, Italy, Netherlands, Spain, Sweden, Switzerland