Early Detection of Metastatic Recurrence Among Patients With Stage II or III Triple Negative Breast Cancer Using Liquid Biopsy and Imaging (EINSTEIN-TNBC)
Early Detection of Metastatic Recurrence Among Patients With Stage II or III Triple Negative Breast Cancer (TNBC) Using Liquid Biopsy and Imaging: A Multi-Center Pilot Randomized Trial (EINSTEIN-TNBC)
Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer, often with poor outcomes. Currently, follow-up for TNBC consists of physical exams and annual breast imaging, with additional scans only if symptoms appear. This approach may delay the detection of the cancer coming back until the disease is advanced.
A promising new technique is the detection of circulating tumor DNA (ctDNA)-in the blood. Studies suggest ctDNA may identify cancer recurrence months before it becomes visible on scans or causes symptoms. However, it is unknown whether detecting recurrence earlier can actually help patients live longer or feel better.
The EINSTEIN-TNBC trial is a study aiming to evaluate the feasibility of ctDNA-guided surveillance for patients with TNBC after surgery.
Thirty participants will be randomized to either:
Standard of care (routine physical exams and annual breast imaging), or Active surveillance (standard of care plus ctDNA testing, with imaging investigations if ctDNA is detected).
This study will assess the feasibility of conducting a ctDNA-based monitoring trial in this patient population.
If feasible, EINSTEIN-TNBC will lay the foundation for a larger future clinical trial to determine whether earlier detection of metastatic TNBC can improve survival and quality of life.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Background:
Triple-negative breast cancer (TNBC) is associated with poor clinical outcomes. In patients with stage II-III TNBC treated with neoadjuvant therapy in the KEYNOTE-522 trial, almost one-third of patients with residual disease died at 5 years. Yet, standard-of-care (SOC) surveillance after curative therapy consists of routine breast imaging and physical examination, with additional imaging performed only upon development of symptoms suggestive of disease recurrence. Given the ability of circulating tumor DNA (ctDNA) to detect metastatic recurrence at its earlier stages, even prior to detection using conventional imaging, it is possible that early detection and intervention for molecular relapse of TNBC may improve patients' outcomes. This pilot trial evaluates the feasibility of a future phase III randomized controlled trial (RCT), which would evaluate whether ctDNA-based surveillance and subsequent early intervention may improve patients' outcomes including overall survival (OS).
Methods:
This is a multi-center, pilot randomized trial conducted at 3 Canadian cancer centers: Sunnybrook Odette Cancer Centre, Princess Margaret Cancer Centre, and William Osler Health System. Inclusion Criteria: 1) Age ≥18; 2) Biopsy-proven invasive TNBC; 3) T2-4/N0 OR T1c-4/N1-3 disease at initial diagnosis; 4) Residual disease (RCB 2 or 3) after curative-intent neoadjuvant chemo(-immuno)therapy. Exclusion Criteria: 1) Inability to provide informed consent; 2) Prior invasive breast cancer; 3) Another malignancy which may interfere with assessment of clinical outcomes; 4) Current pregnancy; 5) Creatinine clearance <45 mL/min. Post-operatively, participants are randomized 1:1 to 'active surveillance' and SOC surveillance. 'Active surveillance' consists of serial ctDNA measurements (specific assay currently embargoed but will be presented) every 3 months for 1 year post-operatively; ctDNA positivity will trigger imaging investigations (i.e. CT chest/abdomen/pelvis with contrast, bone scan, and MRI brain with contrast) every 3 months until detection of overt MBC. Overt MBC will be treated as per SOC. Primary endpoints: 1) Recruitment rate; 2) Proportion of eligible patients approached who agree to participate; 3) Proportion of randomized patients who complete 1 year of follow-up. Secondary Endpoints: 4) MBC incidence; 5) Correlation of ctDNA findings with imaging results; 6) Number and types of diagnostic and/or therapeutic interventions; 7) Quality of life (EORTC QLQ BN20); 8) Patient anxiety (NCI PRO-CTCAE); 9) ctDNA turnaround time; 10) invasive disease-free survival (iDFS); 11) OS; 12) Perceptions of medical oncologists regarding their experience using ctDNA as a monitoring tool.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Katarzyna Jerzak, MD, MSc, FRCPC
- Phone Number: 416-480-5248
- Email: katarzyna.jerzak@sunnybrook.ca
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Men or women aged 18 and over
- Biopsy proven invasive triple negative breast cancer (defined here as estrogen receptor <10%, progesterone receptor <10%, human epidermal growth factor receptor 2 (HER2) negative status, with HER2 status being defined as per ASCO/CAP guidelines)
- T2-4/N0 (>2 cm primary breast cancer as assessed clinically or on imaging in the absence of nodal involvement) OR T1c-4/N1-3 disease (>10mm with fine needle aspirate or core biopsy confirming nodal involvement is required)
- Residual disease (RCB 2 or 3) on surgical specimen after completion of neoadjuvant chemo(-immuno)therapy
Exclusion Criteria:
- Inability to provide informed consent. Participants who require translators are allowed to enroll
- Prior history of invasive breast cancer -Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the detection of BC recurrence on a liquid biopsy (patients with a history of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and carcinoma-in-situ of cervix are permitted to participate)-
- Pregnant patients are not permitted
- Creatinine clearance <45 mL/min using the Cockcroft-Gault equation.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Active Surveillance
ctDNA-guided imaging surveillance, in addition to standard of care surveillance
|
Serial ctDNA measurements post-operatively at time of randomization and every 3 months up to a year, with ctDNA positivity triggering additional imaging investigations (CT chest/abdomen/pelvis with contrast, bone scan, and MRI brain with contrast) every 3 months until detection of overt metastatic breast cancer; overt metastatic breast cancer will be treated as per standard of care.
Standard of care surveillance consists of history and physical examination every 3 months, and routine breast imaging.
|
|
Active Comparator: Standard of care
Standard of care surveillance
|
Standard of care surveillance consists of history and physical examination every 3 months, and routine breast imaging.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Recruitment rate
Time Frame: 24 months
|
24 months
|
|
Proportion of eligible patients approached who agree to participate
Time Frame: 24 months
|
24 months
|
|
Proportion of randomized patients who complete 1 year of follow-up
Time Frame: 36 months
|
36 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Overall survival
Time Frame: 36 months
|
36 months
|
|
|
Incidence of metastatic breast cancer
Time Frame: 36 months
|
36 months
|
|
|
Incidence of radiographic metastatic disease among patients with positive ctDNA
Time Frame: 36 months
|
Assessed by serial CT scans, MRI scans and bone scans, as previously described
|
36 months
|
|
Number and types of diagnostic and/or therapeutic interventions
Time Frame: 36 months
|
36 months
|
|
|
Quality of life (EORTC QLQ BN20)
Time Frame: 36 months
|
36 months
|
|
|
Patient anxiety (NCI PRO-CTCAE)
Time Frame: 36 months
|
36 months
|
|
|
ctDNA turnaround time
Time Frame: 36 months
|
36 months
|
|
|
Invasive disease-free survival
Time Frame: 36 months
|
36 months
|
|
|
Perceptions of medical oncologists regarding their experience using ctDNA as a monitoring tool
Time Frame: 36 months
|
This will be evaluated by the Acceptability of Intervention Measure (AIM) validated tool
|
36 months
|
Collaborators and Investigators
Publications and helpful links
General Publications
- . Nader-Marta, G. et al. Circulating tumor DNA for predicting recurrence in patients with operable breast cancer: a systematic review and meta-analysis. ESMO Open 9, 102390 (2024)
- Pusztai, L. et al. Event-free survival by residual cancer burden with pembrolizumab in early-stage TNBC: exploratory analysis from KEYNOTE-522. Ann. Oncol. 35, 429-436 (2024)
- Schmid, P. et al. Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- EINSTEIN-TNBC
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.