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

NCT00899548 | Completed Results

• 6 other identifiers: J0524P30CA006973JHOC-J0524JHOC-SKCCC-J0524CDR0000509417NA_00000717
• Study Type: observational
• Target: 182
• Locations: 1 country
• Sites: 4

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.

Conditions

Breast Cancer

Keywords

stage IV breast cancer; recurrent breast cancer

Outcome Measures

Primary Outcomes (4)

• Progression-free Survival in Patients With a High vs. Low Cumulative Methylation Index (CMI) Value

  from week 4 to up to 87 months

• Changes in Methylated Gene Markers as Measured by Cumulative Methylation Index

  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.

  baseline, week 4

• Effects of Common Exposures (i.e., Alcohol, Smoking, Medications, and Dietary Factors) on Patterns of Serum Methylation

  9-12 weeks

• Creation of a Predictive Model of DNA Methylation Profiles

  9-12 weeks

Secondary Outcomes (2)

• 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

Other Outcomes (1)

• Determination if the Addition of CTCs to Serum Methylation Results in an Improved Predictive Model

  3-4 weeks

Study Arms (1)

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

Interventions

DNA methylation analysis GENETIC

laboratory analysis

Metastatic breast cancer patients

microarray analysis GENETIC

laboratory analysis

Metastatic breast cancer patients

polymerase chain reaction GENETIC

laboratory analysis

Metastatic breast cancer patients

laboratory biomarker analysis OTHER

laboratory analysis

Metastatic breast cancer patients

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

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

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Cancer Institute (NCI): collaborator

Study Sites (4)

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202-5289, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

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

Chapel Hill, North Carolina, 27599-7295, United States

Location

Related Publications (1)

• 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.

  PMID: 27870562 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Serum, plasma, DNA, RNA, whole blood

MeSH Terms

Conditions

Breast Neoplasms

Interventions

DNA Methylation; Microarray Analysis; Polymerase Chain Reaction

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Methylation; Alkylation; Biochemical Phenomena; Chemical Phenomena; Metabolism; Genetic Phenomena; Microchip Analytical Procedures; Investigative Techniques; Nucleic Acid Amplification Techniques; Genetic Techniques

Results Point of Contact

• Title: Antonio C. Wolff, M.D.
• Organization: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

awolff@jhmi.edu

410-614-4192

Study Officials

• Antonio C. Wolff, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2009
• First Posted: May 12, 2009
• Study Start: January 1, 2007
• Primary Completion: June 1, 2010
• Study Completion: October 1, 2016
• Last Updated: July 26, 2019
• Results First Posted: July 26, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will share
• Time Frame: Not yet determined
• Access Criteria: Not yet determined

Locations

US (4)