DNA in Predicting Response After Systemic Therapy in Women With Metastatic Breast Cancer

July 25, 2019 updated by: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

DNA Methylation in Serum as a Predictive Marker of Progression and Survival Following Systemic Therapy in Patients With Metastatic Breast Cancer

RATIONALE: Studying samples of blood from patients with cancer and from healthy participants in the laboratory may help doctors learn more about changes that may occur in DNA and identify biomarkers related to cancer. It may also help doctors predict how well patients will respond to systemic therapy.

PURPOSE: This laboratory study is looking at DNA in predicting response after systemic therapy in women with metastatic breast cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Identify a panel of methylated gene markers in serum from women with metastatic breast cancer that is significantly different from that observed in healthy participants.
  • Assess changes in a panel of methylated gene markers from baseline, after 3-4 weeks, and after 9-12 weeks of systemic therapy in patients with metastatic breast cancer.
  • Determine the potential effects of common exposures (i.e., alcohol, smoking, medications, and dietary factors) on patterns of serum methylation in patients with metastatic breast cancer and in healthy participants.
  • Develop a predictive model using DNA methylation profiles in serum that predicts clinical outcome for an individual patient with metastatic disease.

Secondary

  • Correlate circulating tumor cells (CTCs) with clinical outcome in patients with metastatic breast cancer.
  • Correlate CTCs with serum methylation in these patients.
  • Determine if the addition of CTCs to serum methylation results in an improved predictive model.

OUTLINE: This is a prospective, multicenter study.

Patients and healthy participants fill out health assessment questionnaires at baseline, week 3-4, and week 9-12.

Patients undergo blood collection for methylated marker analysis at baseline, weeks 3-4, and weeks 9-12 and circulating tumor cell levels at baseline and weeks 3-4. Healthy participants undergo blood collection for methylated marker analysis at baseline. An additional cohort of healthy participants undergo follow-up blood collection ≥ 1 week after baseline.

DNA methylation is measured by quantitative multiplex methylation-specific polymerase chain reaction (QM-MSP) assay.

After completion of study procedures, patients are followed every 3-4 months.

PROJECTED ACCRUAL: A total of 150 patients and 150 healthy participants will be accrued for this study.

Study Type

Observational

Enrollment (Actual)

182

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Indiana
      • Indianapolis, Indiana, United States, 46202-5289
        • Indiana University Melvin and Bren Simon Cancer Center
    • Maryland
      • Baltimore, Maryland, United States, 21231-2410
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic Cancer Center
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599-7295
        • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Probability Sample

Study Population

Metastatic breast cancer patients and women without a history of breast cancer (ie, healthy women or "normals')

Description

DISEASE CHARACTERISTICS:

  • Meets 1 of the following criteria:

    • Histologically and/or cytologically confirmed stage IV adenocarcinoma of the breast (patient)
    • No diagnosis of an abnormal breast biopsy (including atypical ductal or lobular hyperplasia), or new diagnosis of breast cancer or breast cancer recurrence within the past five years (healthy participant)

  • Evidence of disease progression AND initiating a new systemic treatment regimen with trastuzumab (Herceptin®), chemotherapy, endocrine therapy, or investigational agent(s) (patient)

    • Treatment may be given as a single agent or in combination

  • Measurable or evaluable disease (patient)

    • Measurable disease is defined as ≥ 1 measurable lesion identified by RECIST criteria
    • Patients with evaluable disease only must have ≥ 1 tumor marker (e.g., carcinoembryonic antigen, CA 27-29, or CA 15-3) above normal level

  • Treated brain metastases (surgery or radiation therapy) allowed provided patient has evidence of disease stability or presence of other site(s) of measurable or evaluable disease (patient)

    • No leptomeningeal disease
  • Hormone receptor status not specified

PATIENT CHARACTERISTICS:

  • Female
  • Menopausal status not specified
  • ECOG performance status 0-2
  • No known cancer within the past 5 years other than basal cell or squamous cell carcinoma of the skin and/or adequately treated cervical cancer (healthy participant)
  • Not pregnant or nursing

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics

  • Prior therapy in the preoperative, adjuvant, and/or metastatic setting allowed

    • Any number of prior regimens in any setting allowed
  • No prior radiation therapy to the only site of disease unless there is evidence of post-radiation disease progression
  • No selective estrogen receptor modulator or aromatase inhibitor for breast cancer prevention or therapy within the past 12 months (healthy participant)
  • Prior or concurrent use of raloxifene for osteopenia or osteoporosis therapy allowed (healthy participant)
  • Concurrent participation in another clinical trial, including one involving an investigational agent(s), allowed

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Metastatic breast cancer patients
DNA methylation analysis, microarray analysis, polymerase chain reaction, laboratory biomarker analysis
Genetic: DNA methylation analysis
laboratory analysis
Other: laboratory biomarker analysis
laboratory analysis
Genetic: microarray analysis
laboratory analysis
Genetic: polymerase chain reaction
laboratory analysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival in Patients With a High vs. Low Cumulative Methylation Index (CMI) Value
Time Frame: from week 4 to up to 87 months
from week 4 to up to 87 months
Changes in Methylated Gene Markers as Measured by Cumulative Methylation Index
Time Frame: baseline, week 4
log change in cumulative methylation index (CMI) from baseline to week 4. Individual gene methylation (M) is calculated as a methylation index (MI) where MI = (methylated copies)/(number of methylated genes + gene standard copies) * 100. The MI of each sample was averaged across duplicates. The cumulative methylation index (CMI) is the sum of the MI for all genes. The log change from based line to week 4 could increase or decrease. CMI was evaluated as a continuous marker for change from baseline.
baseline, week 4
Effects of Common Exposures (i.e., Alcohol, Smoking, Medications, and Dietary Factors) on Patterns of Serum Methylation
Time Frame: 9-12 weeks
9-12 weeks
Creation of a Predictive Model of DNA Methylation Profiles
Time Frame: 9-12 weeks
9-12 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall Survival in Patients With a High vs. Low CMI Value
Time Frame: from week 4 to up to 3 years
from week 4 to up to 3 years
Correlation of CTCs With Serum Methylation
Time Frame: 3-4 weeks
3-4 weeks

Other Outcome Measures

Outcome Measure
Time Frame
Determination if the Addition of CTCs to Serum Methylation Results in an Improved Predictive Model
Time Frame: 3-4 weeks
3-4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Antonio C. Wolff, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2007

Primary Completion (Actual)

June 1, 2010

Study Completion (Actual)

October 1, 2016

Study Registration Dates

First Submitted

May 9, 2009

First Submitted That Met QC Criteria

May 9, 2009

First Posted (Estimate)

May 12, 2009

Study Record Updates

Last Update Posted (Actual)

July 26, 2019

Last Update Submitted That Met QC Criteria

July 25, 2019

Last Verified

July 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • J0524
  • P30CA006973 (U.S. NIH Grant/Contract)
  • JHOC-J0524 (Other Identifier: SKCCC at Johns Hopkins)
  • JHOC-SKCCC-J0524 (Other Identifier: SKCCC at Johns Hopkins)
  • CDR0000509417 (Other Identifier: NCI PDQ)
  • NA_00000717 (Other Identifier: JHM IRB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Data set will be available upon review and approval by the Correlative Science Review Committee of the Translational Breast Cancer Research Consortium (TBCRC). Inquiries should be addressed to the study chair, Dr. Antonio Wolff

IPD Sharing Time Frame

Not yet determined

IPD Sharing Access Criteria

Not yet determined

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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