A Study to Determine the Clinical Significance of Molecular Detection of Breast Cancer in the Blood of Stage IV Breast Cancer Patients

• ClinicalTrials.gov Identifier: NCT00355316
• Recruitment Status: Completed
• First Posted: July 21, 2006
• Last Update Posted: June 21, 2013
• Sponsor: Washington University School of Medicine
• Collaborator: National Institutes of Health (NIH)
• Information provided by (Responsible Party): Washington University School of Medicine

Study Description

Brief Summary:

This study is designed to determine whether molecular detection of breast cancer cells in the peripheral blood of Stage IV breast cancer patients is a clinically relevant predictor of progression-free and overall survival. Stage IV breast cancer patients who have measurable breast cancer metastases and are initiating a regimen of systemic therapy are eligible for enrollment. Multi-marker real-time RT-PCR analysis will be performed on peripheral blood specimens from 92 breast cancer patients and 120 healthy volunteers. Peripheral blood specimens from breast cancer patients will be obtained at the time of study entry (prior to initiation of systemic therapy) and at serial time points during follow-up. Subjects will be followed longitudinally until death, although the study has been powered so that the primary objective can be addressed after 12 months of follow-up. Healthy volunteers will be asked to provide a blood sample at time of enrollment but will not be followed.

Condition or disease	Intervention/treatment	Phase
Breast Neoplasms	Other: Blood draw	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 224 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: Peripheral Blood Molecular Staging of Breast Cancer: A Prospective Cohort Study Designed to Determine the Clinical Significance of Molecular Detection of Breast Cancer in the Peripheral Blood of Stage IV Breast Cancer Patients
• Study Start Date: November 2005
• Actual Primary Completion Date: November 2012
• Actual Study Completion Date: February 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Stage IV Breast Cancer; Blood draws at baseline before systemic therapy. Blood draw then every 6 weeks for approximately 12 weeks.	Other: Blood draw
Healthy Volunteers; Baseline blood draw.	Other: Blood draw

Outcome Measures

Primary Outcome Measures :

1. The prevalence of breast cancer cells in the peripheral blood [ Time Frame: 1 year ]
   Specifically, it is predicted that 60% of subjects with Stage IV breast cancer will have evidence of breast cancer cells in the peripheral blood by multi-marker real-time RT-PCR analysis, and that these subjects will experience a significantly decreased progression-free and overall survival.

Secondary Outcome Measures :

1. Evaluate the prognostic significance of molecular detection of breast cancer cells in peripheral blood after initiation of systemic therapy. [ Time Frame: Until patient death ]
   Specifically, we will determine if molecular detection of circulating breast cancer cells after the initiation of systemic therapy is associated with a significantly decreased progression-free and overall survival.
2. Quantify baseline molecular marker expression levels in the peripheral blood of healthy volunteers [ Time Frame: Approximately 12 weeks ]
   Determine if baseline molecular marker expression levels are dependent on patient age, race, and/or the presence of benign breast disease.
3. Compare molecular analyses to the results of the CellSeach assay [ Time Frame: Approximately 12 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

Inclusion Criteria - Stage IV breast cancer patients

1. Patient age must be > 21 years.
2. Patient must have a tissue diagnosis of invasive breast cancer.
3. Patient must have documented evidence of metastatic disease.
4. Patient must have measurable lesions.
5. Patients must be initiating systemic therapy. Patients receiving hormonal therapy, and/or chemotherapy alone or in combination with other therapies are eligible.
6. Patient must have an ECOG performance status of 0, 1, or 2.
7. Patient must be available for follow-up.
8. Patient or their authorized legally acceptable representative must consent to be in the study and must have signed and dated an approved consent form which conforms to federal and institutional guidelines.
9. The patient with a previous history of non-breast malignancy is eligible for this study only if the patient meets the following criteria for a cancer survivor. A cancer survivor is eligible provided the following criteria are met: (1) patient has undergone potentially curative therapy for all prior malignancies, (2) patients have been considered disease free for at least 5 years (with the exception of basal cell or squamous cell carcinoma of the skin or carcinoma-in-situ of the cervix).

Inclusion Criteria - Healthy volunteers

A volunteer will be eligible for inclusion in this study only if ALL of the following criteria apply:

1. Volunteer age must be > 21 years.
2. Volunteer or their authorized legally acceptable representative must consent to be in the study and must have signed and dated an approved consent form which conforms to federal and institutional guidelines.
3. Patients with benign breast disease are eligible for enrollment.
4. The volunteer with a previous history of non-breast malignancy is eligible for this study only if the patient meets the following criteria for a cancer survivor. A cancer survivor is eligible provided both of the following criteria are met: (1) patient has undergone potentially curative therapy for all prior malignancies, (2) patient has been considered disease free for at least 5 years (with the exception of basal cell or squamous cell carcinoma of the skin or carcinoma-in-situ of the cervix).

Exclusion Criteria:

Exclusion Criteria - Stage IV breast cancer patients

A patient will be ineligible for inclusion in this study if ANY of the following criteria apply:

1. No documented metastatic disease.
2. No measurable lesions.
3. Bone only and/or brain metastasis.
4. Patient is not initiating a new regimen of systemic therapy.

Contacts and Locations

Locations

United States, Missouri

Washington University School of Medicine

St. Louis, Missouri, United States, 63110

United States, South Carolina

Medical University of South Carolina

Charleston, South Carolina, United States, 29425

Sponsors and Collaborators

Washington University School of Medicine

National Institutes of Health (NIH)

Investigators

• Principal Investigator: William E. Gillanders, M.D.; Washington University School of Medicine

More Information

Additional Information:

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine 

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Mikhitarian, K., W.E. Gillanders, J.S. Almeida, R.H. Martin, J.C. Varela, J.S. Metcalf, D.J. Cole, and M. Mitas. 2005. Relative levels of gene expression are correlated with the ability to detect micrometastatic breast cancer: statistical analysis of data from a multi-institutional prospective cohort study and development of an innovative microarray strategy. Clin Cancer Res In Press.

Mitas M, Almeida JS, Mikhitarian K, Gillanders WE, Lewin DN, Spyropoulos DD, Hoover L, Graham A, Glenn T, King P, Cole DJ, Hawes R, Reed CE, Hoffman BJ. Accurate discrimination of Barrett's esophagus and esophageal adenocarcinoma using a quantitative three-tiered algorithm and multimarker real-time reverse transcription-PCR. Clin Cancer Res. 2005 Mar 15;11(6):2205-14.

Mikhitarian K, Martin RH, Mitas M, Mauldin PD, Palesch Y, Metcalf JS, Cole DJ, Gillanders WE; Mims Study Group. Molecular analysis improves sensitivity of breast sentinel lymph node biopsy: results of a multi-institutional prospective cohort study. Surgery. 2005 Sep;138(3):474-81.

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT00355316
• Other Study ID Numbers: 05-0435 / 201109033
• First Posted: July 21, 2006
• Last Update Posted: June 21, 2013
• Last Verified: June 2013

Keywords provided by Washington University School of Medicine:

Breast Cancer; Peripheral; Blood

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases