DNA in Predicting Response After Systemic Therapy in Women With Metastatic Breast Cancer - Full Text View

Sponsor:	Sidney Kimmel Comprehensive Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by (Responsible Party):	Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00899548

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:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

U.S. FDA Resources

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

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

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Antonio C. Wolff, MD

Sidney Kimmel Comprehensive Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

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:	January 18, 2012
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
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on February 09, 2012