Breast NeoplasmsCOP-BREASTNCT03814811
Circulating Osteocalcin-positive Cells in Breast Cancer Bone Metastasis
An observational study of Breast Neoplasms and Bone Metastases, run by Seoul National University Hospital at 2 sites in South Korea.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 20 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Breast Neoplasms, Bone Metastases
- What is being tested?
- Circulating Osteocalcin-positive (cOC) cells
- How many people
- 200 participants
- Where
- 2 sitesSouth Korea
- Study dates
- 1 Jul 2017to 31 Dec 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Study population: * Patients in Seoul National University Hospital or Korea University Anam Hospital, Seoul, Korea * Residents of the Republic of Korea
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
South Korea2 sites, 2 recruiting
- Recruiting
Korea University Anam Hospital
Seoul, 02841
Kyung Hwa Park, M.D., Ph.D., +82-2-920-6841, katyoncopark@gmail.com
- Recruiting
Seoul National University Hospital
Seoul, 03080
Sun Wook Cho, M.D., Ph.D., +82-2-2072-4761, swchomd@snu.ac.kr
About this study
Official title: 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.
Read the 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.
- Conditions
- Breast Neoplasms, Bone Metastases
- Being tested
- Circulating Osteocalcin-positive (cOC) cells
- Keywords
- Breast Cancer, Bone, Metastasis, Osteoblast
- Medical subject headings
- Breast Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Circulating Osteocalcin-positive (cOC) cellsDiagnostic test
Quantitative measurement of osteocalcin-positive cells in the peripheral blood mononuclear cells by flow cytometry
| Study group | Role | What they receive |
|---|---|---|
| Bone metastasis(+) with low cOC | Patients who have bone metastasis with low number of circulating osteocalcin-positive (cOC) cells Receives: Diagnostic Test: Circulating Osteocalcin-positive (cOC) cells | |
| Bone metastasis(+) with high cOC | Patients who have bone metastasis with high number of circulating osteocalcin-positive (cOC) cells Receives: Diagnostic Test: Circulating Osteocalcin-positive (cOC) cells | |
| Bone metastasis(-) with low cOC | Patients who have metastasis only in extraskeletal sites with low number of circulating osteocalcin-positive (cOC) cells Receives: Diagnostic Test: Circulating Osteocalcin-positive (cOC) cells | |
| Bone metastasis(-) with high cOC | Patients who have metastasis only in extraskeletal sites with high number of circulating osteocalcin-positive (cOC) cells Receives: Diagnostic Test: Circulating Osteocalcin-positive (cOC) cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression of bone metastasis
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
Measured: 18 months after enrollment
Diagnosis of new bone metastasis
De novo bone metastasis will be diagnosed using imaging studies
Measured: 18 months after enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2019
- Study start1 Jul 2017
- Primary completion30 Sep 2017
- Study completion31 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Breast NeoplasmsStudies of the same condition, open and under way.
- More trials run by Seoul National University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Seoul National University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Center, Korea
- Responsible party
- Sponsor
- Investigators
- Sun Wook Cho, M.D., Ph.D., Principal investigator, Seoul National University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03814811
- Sponsor's protocol ID
- SNUH-IRB-1706069859
- Acronym
- COP-BREAST
- Status last verified
- Jan 2019
- First submitted
- 21 Jan 2019
- Last updated
- 24 Jan 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Jeong HM, Cho SW, Park SI. Osteoblasts Are the Centerpiece of the Metastatic Bone Microenvironment. Endocrinol Metab (Seoul). 2016 Dec;31(4):485-492. doi: 10.3803/EnM.2016.31.4.485.
PubMed 28029019Eghbali-Fatourechi GZ, Lamsam J, Fraser D, Nagel D, Riggs BL, Khosla S. Circulating osteoblast-lineage cells in humans. N Engl J Med. 2005 May 12;352(19):1959-66. doi: 10.1056/NEJMoa044264.
PubMed 15888696Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol. 2009 Mar;9(3):162-74. doi: 10.1038/nri2506.
PubMed 19197294Manavalan JS, Cremers S, Dempster DW, Zhou H, Dworakowski E, Kode A, Kousteni S, Rubin MR. Circulating osteogenic precursor cells in type 2 diabetes mellitus. J Clin Endocrinol Metab. 2012 Sep;97(9):3240-50. doi: 10.1210/jc.2012-1546. Epub 2012 Jun 27.
PubMed 22740707
Study at a glance
From the registry record, last updated by the sponsor on 24 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Circulating Osteocalcin-positive Cells as a Cell-Based Biomarker of Breast Cancer Bone Metastasis Progression
- ClinicalTrials.gov ID
- NCT03814811
- Acronym / sponsor ID
- COP-BREAST / SNUH-IRB-1706069859
- Conditions
- Breast Neoplasms, Bone Metastases
- Keywords
- Breast Cancer, Bone, Metastasis, Osteoblast
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Seoul National University HospitalUniversity, hospital or other
- Collaborators
- National Cancer Center, Korea
- Study start
- 1 Jul 2017 (actual)
- Primary completion
- 30 Sep 2017 (actual)
- Study completion
- 31 Dec 2021 (estimated)
- First posted
- 24 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Bone metastasis(+) with low cOC | – | Diagnostic Test: Circulating Osteocalcin-positive (cOC) cellsPatients who have bone metastasis with low number of circulating osteocalcin-positive (cOC) cells |
| Bone metastasis(+) with high cOC | – | Diagnostic Test: Circulating Osteocalcin-positive (cOC) cellsPatients who have bone metastasis with high number of circulating osteocalcin-positive (cOC) cells |
| Bone metastasis(-) with low cOC | – | Diagnostic Test: Circulating Osteocalcin-positive (cOC) cellsPatients who have metastasis only in extraskeletal sites with low number of circulating osteocalcin-positive (cOC) cells |
| Bone metastasis(-) with high cOC | – | Diagnostic Test: Circulating Osteocalcin-positive (cOC) cellsPatients who have metastasis only in extraskeletal sites with high number of circulating osteocalcin-positive (cOC) cells |
Who may qualify
- Ages
- 20 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- * Patients in Seoul National University Hospital or Korea University Anam Hospital, Seoul, Korea * Residents of the Republic of Korea
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Circulating Osteocalcin-positive (cOC) cellsQuantitative measurement of osteocalcin-positive cells in the peripheral blood mononuclear cells by flow cytometry | Diagnostic test | Bone metastasis(+) with high cOC, Bone metastasis(+) with low cOC, Bone metastasis(-) with high cOC, Bone metastasis(-) with low cOC |
Primary outcome
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
Diagnosis of new bone metastasis
Time frame: 18 months after enrollment
De novo bone metastasis will be diagnosed using imaging studies
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jan 2019.
- Background: PubMed 28029019Jeong HM, Cho SW, Park SI. Osteoblasts Are the Centerpiece of the Metastatic Bone Microenvironment. Endocrinol Metab (Seoul). 2016 Dec;31(4):485-492. doi: 10.3803/EnM.2016.31.4.485.
- Background: PubMed 15888696Eghbali-Fatourechi GZ, Lamsam J, Fraser D, Nagel D, Riggs BL, Khosla S. Circulating osteoblast-lineage cells in humans. N Engl J Med. 2005 May 12;352(19):1959-66. doi: 10.1056/NEJMoa044264.
- Background: PubMed 19197294Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol. 2009 Mar;9(3):162-74. doi: 10.1038/nri2506.
- Background: PubMed 22740707Manavalan JS, Cremers S, Dempster DW, Zhou H, Dworakowski E, Kode A, Kousteni S, Rubin MR. Circulating osteogenic precursor cells in type 2 diabetes mellitus. J Clin Endocrinol Metab. 2012 Sep;97(9):3240-50. doi: 10.1210/jc.2012-1546. Epub 2012 Jun 27.
- Individual participant dataSharing planned: No
Related trials for Breast Neoplasms
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sun Wook Cho, M.D., Ph.D. principal investigator
Seoul National University Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Breast Neoplasms and Bone Metastases, run by Seoul National University Hospital at 2 sites in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sun Wook Cho, M.D., Ph.D. (+82-2-2072-4761, swchomd@snu.ac.kr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression of bone metastasis (time frame: 18 months after enrollment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03814811, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jan 2019.