Circulating Tumor DNA: TBCRC-068

Phase 2

Not yet recruiting

• Conditions: ER+ Breast Cancer
• Interventions: Drug: Elacestrant

• Registration Number: NCT06923527
• Lead Sponsor: Yale University

Brief Summary

This is a single-arm, phase II study examining elacestrant in the adjuvant treatment of patients with ER+ breast cancer who test positive for circulating tumor DNA (ctDNA) during the screening period of the trial.

Detailed Description

This is a single-arm, phase II study examining elacestrant in the adjuvant treatment of patients with ER+ breast cancer who test positive for circulating tumor DNA (ctDNA) during the screening period of the trial. Patients with ER+ breast cancer anatomic stage IIB or III at diagnosis who are at least five years from diagnosis and have completed intended course of adjuvant endocrine therapy and are currently off endocrine therapy will be screened with ctDNA testing. Patients who test positive for ctDNA during the screening phase will receive treatment with elacestrant for one year and continue ctDNA testing and imaging with CT scans every three months. During the follow-up period, patients in the study will continue to be ctDNA tested every six months and monitored for one year and will be allowed to continue on elacestrant for an additional year, resume standard endocrine therapy, or continue with standard of care surveillance during follow up.

Study Timeline

• Status Verified: 2025-03
• Study First Submitted: 2025-03-27
• Study Start: 2025-04
• Study First Submitted QC: 2025-04-03
• Last Update Submitted: 2025-04-03
• Study First Posted: 2025-04-11
• Last Update Posted: 2025-04-11
• Primary Completion: 2027-04
• Study Completion: 2027-04

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1. Women or men aged 18 years and older.
2. Previous diagnosis of anatomic stage IIB or anatomic stage III histopathologically or cytologically confirmed ER+, HER2-, breast cancer per local laboratory as per ASCO/CAP guidelines. In the context of this trial, ER status will be considered positive if >10% of tumor cells demonstrate positive nuclear staining by immunohistochemistry, with or without progesterone receptor positivity. Patients who are PR positive but ER-negative are not eligible.
3. Participants must have been diagnosed with ER+HER2- breast cancer at least five years ago and no more than 15 years ago and must have completed adjuvant endocrine therapy.
4. Participants must be off endocrine therapy for at least six months prior to screening.

Exclusion Criteria

1. Known current metastatic disease.

2. Known contraindication to receiving elacestrant as per FDA package insert.

3. Current treatment with endocrine therapy.

4. Prior treatment with elacestrant or other investigational SERDs.

5. Current or past invasive cancer other than breast cancer, except:

   1. Adequately treated basal or squamous cell carcinoma of the skin.
   2. Cancer survivors of previously diagnosed invasive cancer who were treated with curative intent and have no evidence of disease recurrence for five years or more and are considered low risk for future recurrence by the treating physician.

6. Patients in the screening phase, or in the randomized trial (treatment phase), cannot start receiving therapy on another therapeutic clinical trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single Arm	Elacestrant	Administration of elacestrant will follow the FDA approved dose and schedule for patients with ER+ metastatic breast cancer. Elacestrant 345 mg will be administered orally once daily for 12 cycles or until disease progression or unacceptable toxicity

Primary Outcome Measures

Name	Time	Method
Assessing Elacestrant's Impact on ctDNA Clearance in ER+HER2- Breast Cancer Patients	Every 3 months during the treatment phase and at 3-month intervals for 12 months following the end of treatment	This study evaluates whether treatment with elacestrant improves the clearance of circulating tumor DNA (ctDNA) in patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. Patients included in the study have detectable ctDNA in their plasma but show no evidence of metastatic disease on imaging, and the results will be compared against historical control data.
Investigating Elacestrant's Effect on 18-Month Invasive Disease-Free Survival in ER+HER2- Breast Cancer Patients	From the start of treatment through 18 months post-initiation of treatment	To determine whether treatment with elacestrant improves the 18-month invasive disease-free survival rate in patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. The study focuses on patients with detectable circulating tumor DNA (ctDNA) in their plasma but who have no observable metastatic disease on imaging, comparing the outcomes to historical controls.

Secondary Outcome Measures

Name	Time	Method
Patient-Reported Outcomes and Anxiety Levels During Elacestrant Treatment	From baseline through the end of the treatment phase, assessed every 3 months up to 18 months	To evaluate global patient-reported outcomes and anxiety levels during the elacestrant treatment phase.
Incidence of ctDNA Positivity in Screened ER+HER2- Breast Cancer Patients	At baseline screening prior to treatment	To estimate the incidence rate of circulating tumor DNA (ctDNA) positivity among patients screened for the study who have estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer.
Proportion of Patients with Metastatic Disease at First Positive ctDNA Result	From baseline screening through the first positive ctDNA detection, up to 12 months	This secondary outcome measure estimates the proportion of patients who present with clinically apparent metastatic disease (evident on imaging) at the time of their first positive ctDNA result.
Time to Relapse Between First Positive ctDNA and Clinical Recurrence of Metastatic Disease	From the first positive ctDNA detection through clinical recurrence, up to 24 months	To assess the duration between the first detection of positive ctDNA and the clinical recurrence of metastatic disease, as confirmed by imaging.
Association of ctDNA Clearance with Recurrence-Free Survival and Overall Survival	From baseline through 36 months post-treatment initiation	To evaluate whether clearance of ctDNA is associated with improved recurrence-free survival (RFS) and overall survival (OS) in ER+HER2- breast cancer patients
Safety, Tolerability, and Adherence to Elacestrant Treatment Protocol	From baseline through the end of the treatment phase, up to 18 months	To assess the safety and tolerability of the elacestrant treatment, as well as patients' adherence to the treatment protocol.

Trial Locations

Locations (1)

Yale University; 🇺🇸 New Haven, Connecticut, United States