Monitoring Plasma Tumor DNA in Early-Stage Breast Cancer
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|ClinicalTrials.gov Identifier: NCT02743910|
Recruitment Status : Active, not recruiting
First Posted : April 19, 2016
Last Update Posted : January 29, 2020
|Condition or disease||Intervention/treatment|
|Breast Cancer||Other: ptDNA Other: Tissue sample|
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).
|Study Type :||Observational|
|Actual Enrollment :||229 participants|
|Official Title:||Plasma Tumor DNA and Pathologic Complete Response in Early-Stage, High-Risk Breast Cancer|
|Study Start Date :||July 2016|
|Actual Primary Completion Date :||February 2019|
|Estimated Study Completion Date :||March 2024|
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.
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 Name: Blood sample
Other: Tissue sample
Representative tissue sample will be collected from the diagnostic biopsy (in all participants) and definitive surgery (if available)
- Correlation of absence of plasma tumor DNA (ptDNA) with pathologic complete response (pCR) [ Time Frame: 6 months ]
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)
- Prognostic value of ptDNA for invasive disease-free survival and distant disease-free survival [ Time Frame: 5 years ]To estimate the prognostic value of ptDNA for 5-year invasive disease-free survival (IDFS) and distant disease-free survival (DDFS) in TNBC patients following completion of loco-regional and systemic therapy
- Correlation of absence of ptDNA with residual cancer burden (RCB) [ Time Frame: 6 months ]To estimate the NPV of the absence of ptDNA TSMs after NAT for the absence of residual disease as defined by residual cancer burden (RCB) 0 or 1
Biospecimen Retention: Samples With DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02743910
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21287|
|Study Chair:||Ben Ho Park, M.D., Ph.D.||Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|