Clinical Trials /

Monitoring Plasma Tumor DNA in Early-Stage Breast Cancer

NCT02743910

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Trial Eligibility

Document

Title

  • Brief Title: Monitoring Plasma Tumor DNA in Early-Stage Breast Cancer
  • Official Title: Plasma Tumor DNA and Pathologic Complete Response in Early-Stage, High-Risk Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: TBCRC040
  • SECONDARY ID: TBCRC 040
  • SECONDARY ID: IRB00093688
  • NCT ID: NCT02743910

Conditions

  • Breast Cancer

Purpose

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).
    

Trial Arms

NameTypeDescriptionInterventions
Stage II-III breast cancerUp 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.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  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
    
            Exclusion Criteria:
    
              -  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.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Correlation of absence of plasma tumor DNA (ptDNA) with pathologic complete response (pCR)
    Time Frame:6 months
    Safety Issue:
    Description: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)

    Secondary Outcome Measures

    Measure:Prognostic value of ptDNA for invasive disease-free survival and distant disease-free survival
    Time Frame:5 years
    Safety Issue:
    Description: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
    Measure:Correlation of absence of ptDNA with residual cancer burden (RCB)
    Time Frame:6 months
    Safety Issue:
    Description: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

    Details

    Phase:N/A
    Primary Purpose:Observational
    Overall Status:Recruiting
    Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center

    Trial Keywords

    • preoperative
    • neoadjuvant
    • plasma tumor DNA
    • ptDNA

    Last Updated

    January 18, 2018