Circulating Osteocalcin-positive Cells in Breast Cancer Bone Metastasis (COP-BREAST)

January 21, 2019 updated by: Seoul National University Hospital

Circulating Osteocalcin-positive Cells as a Cell-Based Biomarker of Breast Cancer Bone Metastasis Progression

Bone metastasis (i.e. cancer cell spreading to bone) is the major clinical problem of advanced breast cancer patients. Bone metastasis is not curable nor preventable. Currently available therapeutic approaches are only palliative. The major hurdle for improving bone metastasis treatment is lack of sensitive diagnostic tools. Diagnosis of bone metastasis is heavily dependent on radiographic imaging of bone destruction that are detectable only when the lesion is significantly large. Accordingly, if bone metastasis can be detected at an earlier time point when bone destruction is minimal or incipient, treatments can be given earlier and the patients can expect better outcomes. We and others previously have found that a subset of bone-forming cells (i.e. circulating osteocalcin-positive cells) exists in the blood stream of the patients with bone diseases (e.g. bone metastasis and inflammation) or active bone formation (e.g. adolescence) in mouse models anf human samples. Extended from this laboratory observation, this clinical study proposes to test the hypothesis that circulating osteocalcin-positive cells are the early biomarker of breast cancer bone metastasis. For this aim, this study will measure circulating osteocalcin-positive cells in the blood samples of breast cancer patient, and examine whether the measure sensitively detects bone metastasis.

Study Overview

Detailed Description

Bone is the most common site of breast cancer metastasis, and the skeletal-related events (SRE) of bone metastasis such as pathologic fractures, cord compression, hypercalcemia and severe pain, accounting for poor quality of life in the terminal stage of the afflicted patients. Since previous SREs are the major risk factors for subsequent SREs related to serious morbidity and mortality, the early detection of bone metastasis prior to clinical symptoms is essential to the better management of breast cancer patients. Currently, diagnosis of bone metastasis is dependent on imaging modalities such as whole-body bone scintigraphy (WBBS). However, detectability of radionuclide activity in the WBBS depends on gross structural bone destruction resulting from considerable progression of macro-metastasis.

Circulating osteoprogenitor cells that is defined a small monocytic cells expressing osteocalcin, a late osteoblast differentiation marker, had been identified in human peripheral blood mononuclear cells (PBMCs). Flow cytometric analyses of the PBMCs using anti-osteocalcin antibody demonstrated that adolescents who are in the period of rapid bone growth showed higher fractions of osteocalcin-positive cells than adults. Moreover, these cells also positively correlated with pathologic changes of bone turnover in such conditions as fracture, hypoparathyroidism, or diabetes. Collectively, circulating osteoprogenitor cells reflects changes of bone turnover in either physiologic or pathologic status.

The scientific hypothesis of this study is that circulating osteoprogenitor cells increases in the early phase of bone micro-metastasis, and the aim of this clinical study is to investigate the difference of circulating osteoprogenitor cells in metastatic breast cancer with or without bone metastasis. This study will also examine whether the patients who have higher number of osteocalcin-positive cells develop bone metastasis at an earlier time point, to validate the value of circulating osteoprogenitor cells in monitoring and/or predictinng the progression of bone metastasis.

Study Type

Observational

Enrollment (Anticipated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Sun Wook Cho, M.D., Ph.D.
  • Phone Number: +82-2-2072-4761
  • Email: swchomd@snu.ac.kr

Study Contact Backup

  • Name: Young Shin Song, M.D., Ph.D.
  • Phone Number: +82-2-2072-4761
  • Email: yssongmd@gmail.com

Study Locations

      • Seoul, Korea, Republic of, 03080
        • Recruiting
        • Seoul National University Hospital
        • Contact:
      • Seoul, Korea, Republic of, 02841
        • Recruiting
        • Korea University Anam Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Sampling Method

Non-Probability Sample

Study Population

  • Patients in Seoul National University Hospital or Korea University Anam Hospital, Seoul, Korea
  • Residents of the Republic of Korea

Description

Inclusion Criteria:

  • Stages 2A-4 breast cancer patients who are subject to adjuvant chemotherapy or radiotherapy
  • 20 years of age or greater
  • Female
  • Ability to understand the study objectives and willingness to sign written consent
  • ECOG status 0, 1 or 2

Exclusion Criteria:

  • History of primary cancer diagnosis in other sites than breast within 5 years
  • Diseases of bone metabolism including primary hyperparathyroidism, Paget's disease, osteomalacia, osteogenesis imperfecta
  • ECOG status 3 or 4
  • Retraction of written consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Bone metastasis(+) with low cOC
Patients who have bone metastasis with low number of circulating osteocalcin-positive (cOC) cells
Quantitative measurement of osteocalcin-positive cells in the peripheral blood mononuclear cells by flow cytometry
Bone metastasis(+) with high cOC
Patients who have bone metastasis with high number of circulating osteocalcin-positive (cOC) cells
Quantitative measurement of osteocalcin-positive cells in the peripheral blood mononuclear cells by flow cytometry
Bone metastasis(-) with low cOC
Patients who have metastasis only in extraskeletal sites with low number of circulating osteocalcin-positive (cOC) cells
Quantitative measurement of osteocalcin-positive cells in the peripheral blood mononuclear cells by flow cytometry
Bone metastasis(-) with high cOC
Patients who have metastasis only in extraskeletal sites with high number of circulating osteocalcin-positive (cOC) cells
Quantitative measurement of osteocalcin-positive cells in the peripheral blood mononuclear cells by flow cytometry

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression of bone metastasis
Time Frame: 18 months after enrollment
Metastatic bone lesions will be re-evaluated at 18 months using imaging studies such as bone scan, CT, MRI, or PET or incidence of active skeletal-related events (SREs) such as pathologic fracture or progressive neurologic signs
18 months after enrollment
Diagnosis of new bone metastasis
Time Frame: 18 months after enrollment
De novo bone metastasis will be diagnosed using imaging studies
18 months after enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Sun Wook Cho, M.D., Ph.D., Seoul National University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

July 1, 2017

Primary Completion (ACTUAL)

September 30, 2017

Study Completion (ANTICIPATED)

December 31, 2021

Study Registration Dates

First Submitted

January 21, 2019

First Submitted That Met QC Criteria

January 21, 2019

First Posted (ACTUAL)

January 24, 2019

Study Record Updates

Last Update Posted (ACTUAL)

January 24, 2019

Last Update Submitted That Met QC Criteria

January 21, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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