Breast Cancer MetastaticNCT04047459
Investigation of Cancer Cell Extravasation Through mRNA Analysis of Organ-specific Endothelial Cells and Microfluidics
An observational study of Breast Cancer Metastatic, run by I.R.C.C.S Ospedale Galeazzi-Sant'Ambrogio at 1 site in Italy.
Trial summary
The project aims at unraveling the role of organ-specific endothelia mediating the preferential metastasisation of breast cancer cells to bone by using a multi-faceted approach, integrating microfluidics and transcriptomic profiling. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Breast Cancer Metastatic
- What is being tested?
- Tissue samples collection and cells isolation
- How many people
- 31 participants
- Where
- 1 siteItaly
- Study dates
- 6 Jun 2016to 31 May 2018
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients undergoing hip or knee surgery, from whom samples of waste bone and muscle tissues can be harvested.
Who may be able to join
- age between 18-65 years
- patients undergoing cruciate ligament surgery or hip arthroplasty
- subscription of informed consent
Who cannot join
- HIV, HCV, HBV, TPHA viral
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Identification of Novel Genes Involved in Cancer Cell Extravasation by Transcriptional Profiling of Primary Organ-specific Endothelial Cells and in Vitro 3D Models
The project aims at unraveling the role of organ-specific endothelia mediating the preferential metastasisation of breast cancer cells to bone by using a multi-faceted approach, integrating microfluidics and transcriptomic profiling. Based on a recently study published by the investigators [Jeon et al., PNAS 2015], it can be hypothesized that phenotypic differences at the level of organ-specific endothelial cells are able to drive the preferential extravasation of breast cancer cells to specific sites. Hence, the transcriptional profile of primary organ-specific endothelial cells derived from healthy patients (i.e. non-affected by breast cancer) will be analyzed to identify phenotypic differences between organ-specific populations of endothelial cells. These analyses will allow to identify potential target genes involved in the organ-specific extravasation of cancer cells (i.e. genes differentially expressed by endothelia of preferential and non-preferential metastasisation sites). The selected genes will be silenced and the effect of gene silencing will be evaluated through microfluidic in vitro organ-specific 3D models designed to study cancer cell extravasation.
Read the detailed description
In particular, the main aim of the study will be to highlight differences between bone and skeletal muscle microenvironments, which are respectively preferential and non-preferential metastasisation sites for breast cancer cells, in order to identify specific pathways driving breast cancer cells extravasation. To this purpose, differences in the transcriptional profile of ECs derived from bone and muscle endothelium will be investigated. These analyses will be used to select target genes differentially expressed by bone- and muscle-specific ECs. Then, ECs obtained from bone and muscle endothelium will be respectively used to mimic bone and muscle microvessel environments in microfluidic in vitro 3D models allowing for the study of breast cancer cell extravasation. The genes selected according to the results of the transcriptomic analysis (e.g. genes expressed in ECs derived from bone endothelium, but not expressed in ECs derived from muscle endothelium) will be silenced and the effect of gene silencing will be evaluated monitoring breast cancer cell extravasation in order to verify the involvement of the selected genes in this process.
- Conditions
- Breast Cancer Metastatic
- Being tested
- Tissue samples collection and cells isolation
- Keywords
- Organ specific endothelium, Microfluidics, Cancer cell extravasation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tissue samples collection and cells isolationOther
During surgery, leftover samples of bone (femoral head/ trabecular bone tissue) and muscle will be collected. Then they will be sent to the laboratory where isolation of cells will be performed.
| Study group | Role | What they receive |
|---|---|---|
| Patient undergoing prosthetic surgery | Patients undergoing surgery for the insertion of a hip prosthesis or a cruciate ligament reconstruction will be included. On those patients tissue samples collection and cells isolation will be performed Receives: Other: Tissue samples collection and cells isolation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Genes differentially expressed by bone and muscle ECs
Differential expression of genes will be determined by transcriptomic analysis of mRNA (with genome-wide mRNA array tools) derived from bone and muscle ECs
Measured: 31/05/2018
Secondary outcomes (4)
Differences in adhesive properties of bone and muscle ECs
Bone and muscle derived ECs will be compared in terms of immunofluorescent staining for adhesion molecules (ICAM-1, E-selectin)
Measured: 31/05/2018
Differences in cell adhesion between bone and muscle ECs
Bone and muscle derived ECs will be compared in terms of number of cells adhered (neutrophils, ...)
Measured: 31/05/2018
Differences in angiogenic potential between bone and muscle ECs
Bone and muscle derived ECs will be compared in terms of angiogenic sprouting, by analyzing immunofluorescence images
Measured: 31/05/2018
Selection of potential target genes involved in breast cancer metastasis
Differentially expressed genes potentially involved in breast cancer cells extravasation and metastasis formation
Measured: 31/05/2018
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2019
- Study start6 Jun 2016
- Primary completion31 May 2018
- Study completion31 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast Cancer MetastaticStudies of the same condition, open and under way.
- More trials run by I.R.C.C.S Ospedale Galeazzi-Sant'AmbrogioThe 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
- Other
- Time perspective
- Prospective
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- I.R.C.C.S Ospedale Galeazzi-Sant'Ambrogio
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Matteo Moretti, PhD, Principal investigator, IRCCS Istituto Ortopedico Galeazzi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04047459
- Sponsor's protocol ID
- BRCP USA
- Status last verified
- Aug 2019
- First submitted
- 6 Dec 2017
- Last updated
- 6 Aug 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identification of Novel Genes Involved in Cancer Cell Extravasation by Transcriptional Profiling of Primary Organ-specific Endothelial Cells and in Vitro 3D Models
- ClinicalTrials.gov ID
- NCT04047459
- Acronym / sponsor ID
- BRCP USA
- Conditions
- Breast Cancer Metastatic
- Keywords
- Organ specific endothelium, Microfluidics, Cancer cell extravasation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- I.R.C.C.S Ospedale Galeazzi-Sant'AmbrogioUniversity, hospital or other
- Study start
- 6 Jun 2016 (actual)
- Primary completion
- 31 May 2018 (actual)
- Study completion
- 31 May 2018 (actual)
- First posted
- 6 Aug 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.
The project aims at unraveling the role of organ-specific endothelia mediating the preferential metastasisation of breast cancer cells to bone by using a multi-faceted approach, integrating microfluidics and transcriptomic profiling. Based on a recently study published by the investigators [Jeon et al., PNAS 2015], it can be hypothesized that phenotypic differences at the level of organ-specific endothelial cells are able to drive the preferential extravasation of breast cancer cells to specific sites. Hence, the transcriptional profile of primary organ-specific endothelial cells derived from healthy patients (i.e. non-affected by breast cancer) will be analyzed to identify phenotypic differences between organ-specific populations of endothelial cells. These analyses will allow to identify potential target genes involved in the organ-specific extravasation of cancer cells (i.e. genes differentially expressed by endothelia of preferential and non-preferential metastasisation sites). The selected genes will be silenced and the effect of gene silencing will be evaluated through microfluidic in vitro organ-specific 3D models designed to study cancer cell extravasation.
Detailed description
In particular, the main aim of the study will be to highlight differences between bone and skeletal muscle microenvironments, which are respectively preferential and non-preferential metastasisation sites for breast cancer cells, in order to identify specific pathways driving breast cancer cells extravasation. To this purpose, differences in the transcriptional profile of ECs derived from bone and muscle endothelium will be investigated. These analyses will be used to select target genes differentially expressed by bone- and muscle-specific ECs. Then, ECs obtained from bone and muscle endothelium will be respectively used to mimic bone and muscle microvessel environments in microfluidic in vitro 3D models allowing for the study of breast cancer cell extravasation. The genes selected according to the results of the transcriptomic analysis (e.g. genes expressed in ECs derived from bone endothelium, but not expressed in ECs derived from muscle endothelium) will be silenced and the effect of gene silencing will be evaluated monitoring breast cancer cell extravasation in order to verify the involvement of the selected genes in this process.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patient undergoing prosthetic surgery | – | Other: Tissue samples collection and cells isolationPatients undergoing surgery for the insertion of a hip prosthesis or a cruciate ligament reconstruction will be included. On those patients tissue samples collection and cells isolation will be performed |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients undergoing hip or knee surgery, from whom samples of waste bone and muscle tissues can be harvested.
Key inclusion criteria (3 listed)
- age between 18-65 years
- patients undergoing cruciate ligament surgery or hip arthroplasty
- subscription of informed consent
Key exclusion criteria (1 listed)
- HIV, HCV, HBV, TPHA viral
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 |
|---|---|---|
| Tissue samples collection and cells isolationDuring surgery, leftover samples of bone (femoral head/ trabecular bone tissue) and muscle will be collected. Then they will be sent to the laboratory where isolation of cells will be performed. | Other | Patient undergoing prosthetic surgery |
Primary outcome
Genes differentially expressed by bone and muscle ECs
Time frame: 31/05/2018
Differential expression of genes will be determined by transcriptomic analysis of mRNA (with genome-wide mRNA array tools) derived from bone and muscle ECs
4 secondary outcomes
Differences in adhesive properties of bone and muscle ECs
Time frame: 31/05/2018
Differences in cell adhesion between bone and muscle ECs
Time frame: 31/05/2018
Differences in angiogenic potential between bone and muscle ECs
Time frame: 31/05/2018
Selection of potential target genes involved in breast cancer metastasis
Time frame: 31/05/2018
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2019.
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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.
Matteo Moretti, PhD principal investigator
IRCCS Istituto Ortopedico Galeazzi
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Breast Cancer Metastatic, run by I.R.C.C.S Ospedale Galeazzi-Sant'Ambrogio at 1 site in Italy.
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 3 inclusion and 1 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: finished, as of the sponsor's last update on 6 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Genes differentially expressed by bone and muscle ECs (time frame: 31/05/2018). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Aug 2019; AzTrials last refreshed its copy on 8 Nov 2026.