Circulating Tumor DNA Based Minimal Residual Disease Detection for Patients With Early-Stage Breast Cancer

NCT ID: NCT07136493

Last Updated: 2025-11-04

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: NA
• Total Enrollment: 350 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-12
• Study Completion Date: 2028-03-30

Brief Summary

This clinical trial studies how well circulating tumor deoxyribonucleic acid (ctDNA) based minimal residual disease (MRD) detection works for patients with early-stage breast cancer. MRD refers to a very small number of tumor cells that remain in the body during or after treatment. ctDNA refers to small pieces of DNA that are released into a person's blood by tumor cells as they die. Management of patients after cancer surgery remains a clinical dilemma, particularly for cancer detected at earlier stages as many patients are cured by surgery alone. This results in very large clinical trials required to demonstrate a modest benefit from treatment. Using ctDNA MRD testing in early-stage breast cancer patients receiving standard treatment may help researchers identify groups that would benefit from additional therapy, leading to better outcomes.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the pathologic response rate and presence of ctDNA post-neoadjuvant therapy in stage I-III breast cancer patients receiving neoadjuvant systemic therapy followed by curative-intent surgical resection, separately for Subgroup 1A: human epidermal growth factor receptor 2 positive (HER2+) (any estrogen receptor [ER]/progesterone receptor [PR] status) and Subgroup 1B: triple negative breast cancer (TNBC). (Cohort 1) II. To determine ctDNA detectability before and after curative-intent surgical resection in Cohort 2 ER+/any progesterone receptor (PR)/HER2- stage I-III breast cancer patients. (Cohort 2)

SECONDARY OBJECTIVES:

I. To determine ctDNA detectability before and after adjuvant chemotherapy and/or radiation therapy, by cohort and subgroup.

II. To determine ctDNA detectability during the follow-up period of up to 3 years after definitive treatment, by cohort and subgroup.

III. To describe, by cohort and subgroup, the association between detectable ctDNA measured post-neoadjuvant treatment and post-surgery with recurrence free survival (RFS).

IV. To describe, by cohort and subgroup, ctDNA levels at baseline and during neoadjuvant treatment and their association with clinical and pathologic response.

V. To describe, by cohort and subgroup, changes in ctDNA levels during systemic treatment (neoadjuvant and adjuvant) and association with clinical response determined radiographically.

VI. To describe, by cohort and subgroup, the difference in time between ctDNA detection (molecular recurrence) and radiographic evidence of disease recurrence following definitive treatment among patients who achieved undetectable ctDNA levels after surgery.

EXPLORATORY OBJECTIVE:

I. To explore the performance of up to two cancer detection assays - BestSEEK and enACT - in development by Dr. Tomasetti at TGen and City of Hope.

OUTLINE: Patients are assigned to 1 of 2 cohorts.

COHORT 1: Patients undergo collection of blood samples for ctDNA testing at 14-21 days post cycle 1, day 1 of standard of care (SOC) neoadjuvant chemotherapy, on the day of SOC surgery, at 3-6 weeks after SOC surgery, at 1-2 weeks after SOC adjuvant radiation therapy (if receiving), at 2-4 weeks after SOC adjuvant systemic therapy (if receiving), every 3 months for 1 year after surgery, and then every 6 months up to year 3 after surgery. Patients may also undergo collection of tumor tissue during SOC surgery on study.

COHORT 2: Patients undergo collection of blood samples for ctDNA testing on the day of SOC surgery, at 3-6 weeks after SOC surgery, at 1-2 weeks after SOC adjuvant radiation therapy (if receiving), at 2-4 weeks after SOC adjuvant systemic therapy (if receiving), every 3 months for 1 year after surgery, and then every 6 months up to year 3 after surgery. Patients may also undergo collection of tumor tissue during SOC surgery on study.

Conditions

Anatomic Stage I Breast Cancer AJCC v8; Anatomic Stage II Breast Cancer AJCC v8; Anatomic Stage III Breast Cancer AJCC v8; Estrogen Receptor-Positive Breast Carcinoma; HER2-Negative Breast Carcinoma; HER2-Positive Breast Carcinoma; Triple-Negative Breast Carcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SCREENING
• Blinding Strategy: NONE

Study Groups

Cohort 1 (blood collection for ctDNA testing - 1)

Patients undergo collection of blood samples for ctDNA testing at 14-21 days post cycle 1, day 1 of SOC neoadjuvant chemotherapy, on the day of SOC surgery, at 3-6 weeks after SOC surgery, at 1-2 weeks after SOC adjuvant radiation therapy (if receiving), at 2-4 weeks after SOC adjuvant systemic therapy (if receiving), every 3 months for 1 year after surgery, and then every 6 months up to year 3 after surgery. Patients may also undergo collection of tumor tissue during SOC surgery on study.

Group Type: EXPERIMENTAL

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo collection of blood samples for ctDNA testing

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo possible collection of tissue

Electronic Health Record Review

Intervention Type: OTHER

Ancillary studies

Survey Administration

Intervention Type: OTHER

Ancillary studies

Cohort 2 (blood collection for ctDNA testing -2)

Patients undergo collection of blood samples for ctDNA testing on the day of SOC surgery, at 3-6 weeks after SOC surgery, at 1-2 weeks after SOC adjuvant radiation therapy (if receiving), at 2-4 weeks after SOC adjuvant systemic therapy (if receiving), every 3 months for 1 year after surgery, and then every 6 months up to year 3 after surgery. Patients may also undergo collection of tumor tissue during SOC surgery on study.

Group Type: EXPERIMENTAL

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo collection of blood samples for ctDNA testing

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo possible collection of tissue

Electronic Health Record Review

Intervention Type: OTHER

Ancillary studies

Survey Administration

Intervention Type: OTHER

Ancillary studies

Interventions

Biospecimen Collection

Undergo collection of blood samples for ctDNA testing

Intervention Type: PROCEDURE

Biospecimen Collection

Undergo possible collection of tissue

Intervention Type: PROCEDURE

Electronic Health Record Review

Ancillary studies

Intervention Type: OTHER

Survey Administration

Ancillary studies

Intervention Type: OTHER

Other Intervention Names

Biological Sample Collection; Biospecimen Collected; Specimen Collection; Biological Sample Collection; Biospecimen Collected; Specimen Collection

Eligibility Criteria

Inclusion Criteria

• Documented written informed consent of the participant
• Age ≥ 18 years
• Diagnosis of stage I-III breast cancer (any gender)
• Malignancy must be epithelial. Non-epithelial breast malignancies such as lymphoma or sarcoma are not allowed
• Willingness to:

• Provide blood samples
• Provide archival tumor tissue sample (only necessary for Cohort 2 if analysis of surgical tissue was not successful)
• Provide tumor tissue sample from resection/surgery (only necessary for Cohort 1 if analysis of surgical tissue was not successful)
• Permit medical record review
• Fall into one of the following categories defined below: Cohort 1, Subgroup A or B OR Cohort 2
• COHORT 1: Must have archival diagnostic tissue available
• COHORT 1: Scheduled to undergo, but has not yet begun, neoadjuvant systemic therapy followed by curative resection
• COHORT 1 (Subgroup A): HER2+ by current American Society of Clinical Oncology (ASCO)/College of American Pathologist (CAP) guidelines (any ER/PR status)
• COHORT 1 (Subgroup B): Triple negative (ER, PR and HER2 negative). Defined as ER and PR ≤ 10% by immunohistochemistry (IHC) and HER2 negative, by current ASCO/CAP guidelines
• COHORT 2: Scheduled to undergo upfront curative surgical resection with or without adjuvant chemotherapy followed by adjuvant endocrine therapy
• COHORT 2: ER+/any PR/HER2- (ER positive defined as ER > 10% by IHC)

Exclusion Criteria

• Ductal carcinoma in situ
• Inability to safely provide sequential blood samples
• Prior or concurrent invasive malignancy (unless disease free > 5 years)
• An employee who is under the direct/ indirect supervision of the principal investigator (PI)/ a co-investigator/ the study manager
• A direct study team member
• Inability to give informed consent

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

City of Hope Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jose G Bazan

Role: PRINCIPAL_INVESTIGATOR

City of Hope Comprehensive Cancer Center

Locations

CTCA at Western Regional Medical Center

Goodyear, Arizona, United States

City of Hope Comprehensive Cancer Center

Duarte, California, United States

City of Hope at Irvine Lennar

Irvine, California, United States

City of Hope Atlanta Cancer Center

Newnan, Georgia, United States

City of Hope at Chicago

Zion, Illinois, United States

Countries

United States

Other Identifiers

NCI-2025-05431

Identifier Type: REGISTRY

Identifier Source: secondary_id

24463

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

24463

Identifier Type: -

Identifier Source: org_study_id