DNA in Predicting Response After Systemic Therapy in Women With Metastatic Breast Cancer
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|ClinicalTrials.gov Identifier: NCT00899548|
Recruitment Status : Completed
First Posted : May 12, 2009
Results First Posted : July 26, 2019
Last Update Posted : July 26, 2019
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 or disease||Intervention/treatment|
|Breast Cancer||Genetic: DNA methylation analysis Genetic: microarray analysis Genetic: polymerase chain reaction Other: laboratory biomarker analysis|
- 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.
- 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|
|Actual Enrollment :||182 participants|
|Official Title:||DNA Methylation in Serum as a Predictive Marker of Progression and Survival Following Systemic Therapy in Patients With Metastatic Breast Cancer|
|Actual Study Start Date :||January 2007|
|Actual Primary Completion Date :||June 2010|
|Actual Study Completion Date :||October 2016|
Metastatic breast cancer patients
DNA methylation analysis, microarray analysis, polymerase chain reaction, laboratory biomarker analysis
Genetic: DNA methylation analysis
Genetic: microarray analysis
Genetic: polymerase chain reaction
Other: laboratory biomarker analysis
- 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 ]
- 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.
- Effects of Common Exposures (i.e., Alcohol, Smoking, Medications, and Dietary Factors) on Patterns of Serum Methylation [ Time Frame: 9-12 weeks ]
- Creation of a Predictive Model of DNA Methylation Profiles [ Time Frame: 9-12 weeks ]
- Overall Survival in Patients With a High vs. Low CMI Value [ Time Frame: from week 4 to up to 3 years ]
- Correlation of CTCs With Serum Methylation [ Time Frame: 3-4 weeks ]
- Determination if the Addition of CTCs to Serum Methylation Results in an Improved Predictive Model [ Time Frame: 3-4 weeks ]
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): NCT00899548
|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|
|Principal Investigator:||Antonio C. Wolff, MD||Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|