NCT02743910

Monitoring Plasma Tumor DNA in Early-Stage Breast Cancer

Plasma Tumor DNA and Pathologic Complete Response in Early-Stage, High-Risk Breast Cancer

• Status: Active Not Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 229 (actual)
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

This is a prospectively designed study. Up to 229 newly diagnosed invasive HER2-positive or triple-negative breast cancer patients planning neoadjuvant therapy (NAT) will be enrolled. Blood samples will be collected pre-operatively 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. Researchers will also collect representative tissue samples from the diagnostic biopsy (in all participants) and definitive surgery (if available). Additionally, to look at feasibility of tumor DNA analyses in urine samples, urine samples will be collected along with blood samples (urine tumor DNA or utDNA). Next generation sequencing will be performed on core biopsies of all enrolled patients for tumor-specific mutations (TSM) discovery. Based on those findings, droplet digital PCR (ddPCR) on plasma DNA samples will also be performed to confirm the presence of the TSM in the plasma on diagnosis, and one TSM will be chosen to track as the plasma tumor DNA (ptDNA) mutation of interest. Investigators will perform ddPCR on pre-operative plasma DNA samples and will assess for the presence of ptDNA. Pathologists will assess surgical specimens for pathologic response (such as complete response/pCR and residual cancer burden/RCB). As primary endpoint, investigators will assess the number of patients with and without preoperative ptDNA who have pCR versus residual disease. As exploratory endpoints, the following will also be performed: (a) quantitative multiplex methylation-specific PCR (QM-MSP) in diagnostic biopsy and definitive residual surgery specimen; and, (b) the circulating methylated tumor DNA (cMethDNA) assay in plasma specimens (baseline and after NAT), and evaluate associations with pathologic response. Additional endpoints include the association between plasma and tissue markers at baseline, after NAT, and (if available) during surveillance with long-term prognosis (invasive disease-free survival/IDFS and distant disease-free survival/DDFS).

Conditions

• Breast Cancer

Interventions

Type	Name	Description
OTHER	ptDNA	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.
OTHER	Tissue sample	Representative tissue sample will be collected from the diagnostic biopsy (in all participants) and definitive surgery (if available)

Timeline

• Start date: 2016-07-01
• Primary completion: 2019-02-01
• Completion: 2026-07-01
• First posted: 2016-04-19
• Last updated: 2025-07-17

Locations

1 site across 1 country: United States