Monitoring Plasma Tumor DNA in Early-Stage Breast Cancer

NCT02743910 | Active Not Recruiting

• 3 other identifiers: TBCRC040TBCRC 040IRB00093688
• Study Type: observational
• Target: 229
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being done to see if it is possible to use blood samples to predict response to treatment in breast cancer patients receiving preoperative (or neoadjuvant) therapy. Research has shown that most breast cancers release tumor-specific DNA into the blood (that is, DNA that is specific to the tumor cells or cancer). This DNA can be detected in blood testing known as plasma tumor-DNA or "ptDNA." This DNA is separate from that found in the blood and tissue samples which serve as the "instruction book" or "genetic code" for the cells that make-up the human body. The changes in ptDNA before and after treatment, as well as after surgery, may also help investigators to understand more about a patient's risk of cancer returning and long-term outcomes.

Conditions

Breast Cancer

Keywords

preoperative; neoadjuvant; plasma tumor DNA; ptDNA

Outcome Measures

Primary Outcomes (1)

• Correlation of absence of plasma tumor DNA (ptDNA) with pathologic complete response (pCR)

  To estimate the negative predictive value (NPV) of the absence of plasma tumor DNA (ptDNA) Tumor Specific Mutations (TSMs) after neoadjuvant therapy (NAT) for the absence of residual disease as defined by pathologic complete response (pCR) in stage II-III HER2-positive or triple negative breast cancer (TNBC) NPV = True Negative/True Negative + False Negative (probability that the disease is not present when the test is negative)

  6 months

Secondary Outcomes (2)

• Prognostic value of ptDNA for invasive disease-free survival and distant disease-free survival

  5 years

• Correlation of absence of ptDNA with residual cancer burden (RCB)

  6 months

Study Arms (1)

Stage II-III breast cancer

Up to 229 newly diagnosed stage II-III invasive HER2-positive or triple-negative breast cancer patients planning neoadjuvant therapy (NAT) will be enrolled. ptDNA blood samples as well as a representative tumor tissue sample from both the diagnostic and surgical procedure (if available) will be collected.

Other: ptDNA; Other: Tissue sample

Interventions

ptDNA OTHER

Pre-operative blood samples for ptDNA will be collected at the time of diagnosis/prior to NAT, post-cycle 1/pre-cycle 2 of NAT, after all NAT/immediately before surgery, and post-operatively at 6, 12, 24, and 36 months, and annually thereafter if funding allows.

Also known as: Blood sample

Stage II-III breast cancer

Tissue sample OTHER

Representative tissue sample will be collected from the diagnostic biopsy (in all participants) and definitive surgery (if available)

Stage II-III breast cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Newly diagnosed invasive HER2-positive or triple-negative breast cancer patients planning neoadjuvant therapy (NAT)

You may qualify if:

• Newly diagnosed, histologically confirmed invasive breast cancer that is triple negative (estrogen receptor \[ER\], progesterone receptor \[PR\], and HER2-neu negative) or HER2-positive (any ER/PR status)
• Unresected, untreated breast cancer that is T2, T3, or T4a-c; any N (nodal status); and M0 (not metastatic)
• ECOG Performance Status of 0 or 1
• Planning to receive a neoadjuvant chemotherapy regimen containing a taxane ± an anthracycline for at least 4 cycles. Patients with HER2-positive disease must also be planning to receive HER2-targeted therapy.
• Diagnostic tumor material must be available for correlative analyses
• Patients must have the ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• No prior treatment for the current breast cancer, though prior use of selective estrogen receptor modulators (SERMs) or aromatase inhibitors (AIs) for the prevention of breast cancer is acceptable.
• Women who are pregnant or nursing are excluded.
• No history of another primary malignancy in the last 5 years prior to registration. Patients with prior history of in situ cancer or basal or localized squamous cell skin cancer are eligible.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Translational Breast Cancer Research Consortium: collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood and tissue samples

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Blood Specimen Collection; Histocompatibility Testing

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Immunologic Tests; Immunologic Techniques

Study Officials

• Antonio C Wolff, M.D.

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2016
• First Posted: April 19, 2016
• Study Start: July 1, 2016
• Primary Completion: February 1, 2019
• Study Completion (Estimated): July 1, 2026
• Last Updated: July 17, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)