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

NCT ID: NCT00899548

Last Updated: 2019-07-26

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 182 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2016-10-31

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.

Conditions

Breast Cancer

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Metastatic breast cancer patients

DNA methylation analysis, microarray analysis, polymerase chain reaction, laboratory biomarker analysis

DNA methylation analysis

Intervention Type: GENETIC

laboratory analysis

microarray analysis

Intervention Type: GENETIC

laboratory analysis

polymerase chain reaction

Intervention Type: GENETIC

laboratory analysis

laboratory biomarker analysis

Intervention Type: OTHER

laboratory analysis

Interventions

DNA methylation analysis

laboratory analysis

Intervention Type: GENETIC

microarray analysis

laboratory analysis

Intervention Type: GENETIC

polymerase chain reaction

laboratory analysis

Intervention Type: GENETIC

laboratory biomarker analysis

laboratory analysis

Intervention Type: OTHER

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Antonio C. Wolff, MD

Role: PRINCIPAL_INVESTIGATOR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, United States

Countries

United States

References

Visvanathan K, Fackler MS, Zhang Z, Lopez-Bujanda ZA, Jeter SC, Sokoll LJ, Garrett-Mayer E, Cope LM, Umbricht CB, Euhus DM, Forero A, Storniolo AM, Nanda R, Lin NU, Carey LA, Ingle JN, Sukumar S, Wolff AC. Monitoring of Serum DNA Methylation as an Early Independent Marker of Response and Survival in Metastatic Breast Cancer: TBCRC 005 Prospective Biomarker Study. J Clin Oncol. 2017 Mar;35(7):751-758. doi: 10.1200/JCO.2015.66.2080. Epub 2016 Nov 21.

Reference Type: RESULT

PMID: 27870562 (View on PubMed)

Other Identifiers

P30CA006973

Identifier Type: NIH

Identifier Source: secondary_id

View Link

JHOC-J0524

Identifier Type: OTHER

Identifier Source: secondary_id

JHOC-SKCCC-J0524

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000509417

Identifier Type: OTHER

Identifier Source: secondary_id

NA_00000717

Identifier Type: OTHER

Identifier Source: secondary_id

J0524

Identifier Type: -

Identifier Source: org_study_id