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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00899548
First received: May 9, 2009
Last updated: March 14, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention
Breast Cancer
Genetic: DNA methylation analysis
Genetic: microarray analysis
Genetic: polymerase chain reaction
Other: laboratory biomarker analysis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: DNA Methylation in Serum as a Predictive Marker of Progression and Survival Following Systemic Therapy in Patients With Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • Correlation of changes in gene marker methylation with progression at 9-12 weeks [ Time Frame: 9-12 weeks ] [ Designated as safety issue: No ]
  • Changes in methylated gene markers from baseline, after 3-4 weeks, and after 9-12 weeks [ Time Frame: 9-12 weeks ] [ Designated as safety issue: No ]
  • Effects of common exposures (i.e., alcohol, smoking, medications, and dietary factors) on patterns of serum methylation [ Time Frame: 9-12 weeks ] [ Designated as safety issue: No ]
  • Creation of a predictive model of DNA methylation profiles [ Time Frame: 9-12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Correlation of gene marker methlyation with survival [ Time Frame: 9-12 weeks, survival ] [ Designated as safety issue: No ]
  • Correlation of gene marker methlyation with time to progression [ Time Frame: 9-12 weeks ] [ Designated as safety issue: No ]
  • Correlation of circulating tumor cells (CTCs) with clinical outcome [ Time Frame: 3-4 weeks ] [ Designated as safety issue: No ]
  • Correlation of CTCs with serum methylation [ Time Frame: 3-4 weeks ] [ Designated as safety issue: No ]
  • Determination if the addition of CTCs to serum methylation results in an improved predictive model [ Time Frame: 3-4 weeks ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Serum, plasma, DNA, RNA, whole blood


Estimated Enrollment: 300
Study Start Date: September 2006
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Metastatic breast cancer patients Genetic: DNA methylation analysis
laboratory analysis
Genetic: microarray analysis
laboratory analysis
Genetic: polymerase chain reaction
laboratory analysis
Other: laboratory biomarker analysis
laboratory analysis
Normals/Controls Genetic: DNA methylation analysis
laboratory analysis
Genetic: microarray analysis
laboratory analysis
Genetic: polymerase chain reaction
laboratory analysis
Other: laboratory biomarker analysis
laboratory analysis

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

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

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00899548

Locations
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202-5289
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, North Carolina
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7295
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Principal Investigator: Antonio C. Wolff, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00899548     History of Changes
Other Study ID Numbers: JHOC-J0524, CDR0000509417, P30CA006973, JHOC-J0524, JHOC-SKCCC-J0524
Study First Received: May 9, 2009
Last Updated: March 14, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
stage IV breast cancer
recurrent breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases

ClinicalTrials.gov processed this record on October 20, 2014