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

Completed

• Conditions: Breast Cancer
• Interventions: Genetic: DNA methylation analysis; Genetic: microarray analysis; Genetic: polymerase chain reaction; Other: laboratory biomarker analysis

• Registration Number: NCT00899548
• Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary

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.

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 Timeline

• Study Start: 2007-01
• Study First Submitted: 2009-05-09
• Study First Submitted QC: 2009-05-09
• Study First Posted: 2009-05-12
• Primary Completion: 2010-06
• Study Completion: 2016-10
• Results First Submitted: 2017-11-01
• Status Verified: 2019-07
• Results First Submitted QC: 2019-07-25
• Last Update Submitted: 2019-07-25
• Results First Posted: 2019-07-26
• Last Update Posted: 2019-07-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 182

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Metastatic breast cancer patients	microarray analysis	DNA methylation analysis, microarray analysis, polymerase chain reaction, laboratory biomarker analysis
Metastatic breast cancer patients	DNA methylation analysis	DNA methylation analysis, microarray analysis, polymerase chain reaction, laboratory biomarker analysis
Metastatic breast cancer patients	polymerase chain reaction	DNA methylation analysis, microarray analysis, polymerase chain reaction, laboratory biomarker analysis
Metastatic breast cancer patients	laboratory biomarker analysis	DNA methylation analysis, microarray analysis, polymerase chain reaction, laboratory biomarker analysis

Primary Outcome Measures

Name	Time	Method
Effects of Common Exposures (i.e., Alcohol, Smoking, Medications, and Dietary Factors) on Patterns of Serum Methylation	9-12 weeks
Changes in Methylated Gene Markers as Measured by Cumulative Methylation Index	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.
Progression-free Survival in Patients With a High vs. Low Cumulative Methylation Index (CMI) Value	from week 4 to up to 87 months
Creation of a Predictive Model of DNA Methylation Profiles	9-12 weeks

Secondary Outcome Measures

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

Trial Locations

Locations (4)

Indiana University Melvin and Bren Simon Cancer Center; 🇺🇸 Indianapolis, Indiana, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; 🇺🇸 Baltimore, Maryland, United States

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States

Mayo Clinic Cancer Center; 🇺🇸 Rochester, Minnesota, United States