Breast CancerNCT02393833
IBCSG Trial 22-00 Serum Substudy
A study testing Blood samples collection in people with Breast Cancer, run by ETOP IBCSG Partners Foundation at 3 sites in 3 countries.
Trial summary
The serum protein research study is a substudy of the core study 'Maintenance Chemotherapy in Hormone Non-responsive Breast Cancer'. This substudy is an evaluation of blood proteins and their relationship to breast cancer treatment. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Blood samples collection
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 136 participants
- Where
- 3 sitesin 3 countries
- Study dates
- Jun 2002to 6 Mar 2018
- Phase
- Interventional
- 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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient must be randomized to the core protocol. Written informed consent for the serum substudy must be signed and dated by the patient and investigator
- Patient must not have begun CM maintenance (if randomized to CM maintenance)
Who cannot join
- Patient not randomized to the core protocol
- Patient already begun CM maintenance (if randomized to CM maintenance)
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
About this study
Official title: Assessment of Vascular Endothelial Growth Factor (VEGF), Soluble Her2 Protein (NRP, Neu-Related Protein), and Vascular Cellular Adhesion Molecule-1 (VCAM-1) in Serum Samples of Patients Participating in Trial IBCSG 22-00
The serum protein research study is a substudy of the core study 'Maintenance Chemotherapy in Hormone Non-responsive Breast Cancer'. This substudy is an evaluation of blood proteins and their relationship to breast cancer treatment. It will assess the levels of Vascular Endothelial Growth Factor (VEGF), Soluble HER2 Protein (NRP, neu-related protein) and Vascular Cellular Adhesion Molecule-1 (VCAM-1) in serum samples of patients' blood at different time points. The goal is to evaluate differences in serum levels between patients receiving the maintenance chemotherapy and those who do not. The serum levels will be also examined to determine if they vary during the three year period of evaluation. In addition, the serum levels of patients who have a recurrence of their breast cancer will be compared with those who remain disease free. The information obtained from these studies will enable breast cancer physicians to better tailor therapies for future patients.
Read the detailed description
The Serum Substudy will assess the levels of Vascular Endothelial Growth Factor (VEGF), Soluble HER2 Protein (NRP, neu-related protein) and Vascular Cellular Adhesion Molecule-1 (VCAM-1) in patients' serum samples at different time points.
VEGF: Angiogenesis plays a central role in tumor progression of solid neoplasia. The switch from the avascular to the vascular phase is generally accompanied by rapid primary tumor growth and local invasiveness. Furthermore, angiogenesis is also necessary both at the beginning and end of the development of distant metastasis and is implicated in the phenomenon of dormant micrometastases. Antiangiogenic peptides may be altered in the serum or urine of cancer patients. In a study of 144 breast cancer patients, angiogenic protein basic fibroblast growth factor was abnormally elevated in the urine in 29% of cases and in the serum in 10%. Another angiogenic protein, vascular endothelial factor (VEGF), was abnormally elevated in the serum in over 70% of these breast cancer patients (4). Since platelets bind VEGF, platelet values will also be assayed.
HER2-ECD: No data are available regarding the presence of serum HER2-ECD (NRP) levels in c-erbB2 negative tumors, but the extracellular domain of the c-erbB2 oncogene product (NRP) is detectable in sera of 30-60% of patients with cerbB2 positive tumors. Many reports have correlated the elevated serum levels of the cerbB2 with gene amplification and c-erbB2 overexpression in tumor. These data support the hypothesis that the level of NRP protein can reflect the presence of c-erbB2 positive cells and that modification of the factor can predict a decrease of c-erbB2 positive cells during standard adjuvant chemotherapy. Moreover, change in the detectable NRP during the maintenance phase can suggest a possible modification in the biology and/or behaviour of hypothetic micrometastasis.
VCAM-1: In tumors, endothelial VCAM-1 play a major role in the adhesion of leukocytes to the endothelium, suggesting a relationship between cellular adhesion and angiogenesis. Soluble VCAM-1 has been implicated in the mediation of angiogenesis and some studies support the hypothesis that VCAM-1 provides surrogate markers for endothelial activation and angiogenesis occurring during cancers. Recently, VCAM-1 serum levels have been associated with microvessel density and response to endocrine therapy.
- Conditions
- Breast Cancer
- Being tested
- Blood samples collection
- Keywords
- Vascular endothelial growth factor (VEGF), Vascular cell adhesion molecule-1 (VCAM-1), HER2-ECD
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood samples collectionProcedure or surgery
Blood samples to be collected at the following time points:
- Baseline, (after the completion of induction chemotherapy and, if randomized to CM maintenance, before start of CM maintenance.)
- Months 12, 18 and 36 after start of induction chemotherapy
- At time of confirmatory evidence of progression
| Study group | Role | What they receive |
|---|---|---|
| Induction chemotherapy | Active comparator | Approved induction CT regimen after randomization Receives: Procedure: Blood samples collection |
| Induction chemotherapy followed by CM maintenance | Experimental | Approved induction chemotherapy followed by 12 months of CM maintenance Receives: Procedure: Blood samples collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline to 18 months in serum VEGF values
To evaluate differences from baseline (after completion of induction chemotherapy but before commencement of CM Maintenance for patients randomized to CM Maintenance) to 18 months after the start of induction chemotherapy in serum VEGF values between patients in the Observation Group and those in the low dose Cyclophosphamide Methotrexate (CM) Maintenance Group.
Measured: 18 months
Change from baseline to 18 months in serum VCAM-1 values
To evaluate differences from baseline (after completion of induction chemotherapy but before commencement of CM Maintenance for patients randomized to CM Maintenance) to 18 months after the start of induction chemotherapy in serum VCAM-1 values between patients in the Observation Group and those in the low dose Cyclophosphamide Methotrexate (CM) Maintenance Group.
Measured: 18 months
Change from baseline to 18 months in serum NRP values
To evaluate differences from baseline (after completion of induction chemotherapy but before commencement of CM Maintenance for patients randomized to CM Maintenance) to 18 months after the start of induction chemotherapy in serum NRP values between patients in the Observation Group and those in the low dose Cyclophosphamide Methotrexate (CM) Maintenance Group.
Measured: 18 months
Secondary outcomes (6)
Change from baseline to 12 and 36 months in serum VEGF values
To compare the differences from baseline to 12 and 36 months in serum VEGF values in the two randomized groups.
Measured: 12 & 36 months
Change from baseline to 12 and 36 months in serum VCAM-1 values
To compare the differences from baseline to 12 and 36 months in serum VCAM-1 values in the two randomized groups.
Measured: 12 & 36 months
Change from baseline to 12 and 36 months in serum NRP values
To compare the differences from baseline to 12 and 36 months in serum NRP values in the two randomized groups.
Measured: 12 & 36 months
Change in serum VEGF values from last measurement before progression to measurement at time of confirmatory evidence of progression
To compare VEGF values before and after progression in the two randomized groups.
Measured: Baseline,12-, 18- or 36-months & progression
Change in serum VCAM-1 values from last measurement before progression to measurement at time of confirmatory evidence of progression
To compare VCAM-1 values before and after progression in the two randomized groups.
Measured: Baseline,12-, 18- or 36-months & progression
Change in serum NRP values from last measurement before progression to measurement at time of confirmatory evidence of progression
To compare NRP values before and after progression in the two randomized groups.
Measured: Baseline,12-, 18- or 36-months & progression
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2015 (estimated)
- Study startJun 2002
- Primary completion6 Mar 2018
- Study completion6 Mar 2018
Why it stopped: Sufficient statistical power cannot be met due to low samples size
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 CancerStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 136 participants (actual)
Sponsor and investigators
- Lead sponsor
- ETOP IBCSG Partners Foundation
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Aron Goldhirsch, Prof., Study chair, IEO MilanoGiuseppe Viale, Prof., Study chair, IEO Milano
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02393833
- Sponsor's protocol ID
- IBCSG 22-00 Serum Substudy
- Other IDs
- 2005-005666-36, IBCSG 22-00, 2005
- Status last verified
- May 2021
- First submitted
- 12 Mar 2014
- Last updated
- 12 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Kern FG, Lippman ME. The role of angiogenic growth factors in breast cancer progression. Cancer Metastasis Rev. 1996 Jun;15(2):213-9. doi: 10.1007/BF00437474. No abstract available.
PubMed 8842493Gasparini G. Clinical significance of the determination of angiogenesis in human breast cancer: update of the biological background and overview of the Vicenza studies. Eur J Cancer. 1996 Dec;32A(14):2485-93. doi: 10.1016/s0959-8049(96)00376-0. No abstract available.
PubMed 9059337Revillion F, Hebbar M, Bonneterre J, Peyrat JP. Plasma c-erbB2 concentrations in relation to chemotherapy in breast cancer patients. Eur J Cancer. 1996 Feb;32A(2):231-4. doi: 10.1016/0959-8049(95)00568-4.
PubMed 8664033Byrne GJ, Ghellal A, Iddon J, Blann AD, Venizelos V, Kumar S, Howell A, Bundred NJ. Serum soluble vascular cell adhesion molecule-1: role as a surrogate marker of angiogenesis. J Natl Cancer Inst. 2000 Aug 16;92(16):1329-36. doi: 10.1093/jnci/92.16.1329.
PubMed 10944555
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Vascular Endothelial Growth Factor (VEGF), Soluble Her2 Protein (NRP, Neu-Related Protein), and Vascular Cellular Adhesion Molecule-1 (VCAM-1) in Serum Samples of Patients Participating in Trial IBCSG 22-00
- ClinicalTrials.gov ID
- NCT02393833
- Acronym / sponsor ID
- IBCSG 22-00 Serum Substudy
- Conditions
- Breast Cancer
- Keywords
- Vascular endothelial growth factor (VEGF), Vascular cell adhesion molecule-1 (VCAM-1), HER2-ECD
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sufficient statistical power cannot be met due to low samples size
- Enrolment
- 136 participants (actual)
- Lead sponsor
- ETOP IBCSG Partners FoundationResearch network
- Study start
- Jun 2002
- Primary completion
- 6 Mar 2018 (actual)
- Study completion
- 6 Mar 2018 (actual)
- First posted
- 19 Mar 2015 (estimated)
- 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 serum protein research study is a substudy of the core study 'Maintenance Chemotherapy in Hormone Non-responsive Breast Cancer'. This substudy is an evaluation of blood proteins and their relationship to breast cancer treatment. It will assess the levels of Vascular Endothelial Growth Factor (VEGF), Soluble HER2 Protein (NRP, neu-related protein) and Vascular Cellular Adhesion Molecule-1 (VCAM-1) in serum samples of patients' blood at different time points. The goal is to evaluate differences in serum levels between patients receiving the maintenance chemotherapy and those who do not. The serum levels will be also examined to determine if they vary during the three year period of evaluation. In addition, the serum levels of patients who have a recurrence of their breast cancer will be compared with those who remain disease free. The information obtained from these studies will enable breast cancer physicians to better tailor therapies for future patients.
Detailed description
The Serum Substudy will assess the levels of Vascular Endothelial Growth Factor (VEGF), Soluble HER2 Protein (NRP, neu-related protein) and Vascular Cellular Adhesion Molecule-1 (VCAM-1) in patients' serum samples at different time points.
VEGF: Angiogenesis plays a central role in tumor progression of solid neoplasia. The switch from the avascular to the vascular phase is generally accompanied by rapid primary tumor growth and local invasiveness. Furthermore, angiogenesis is also necessary both at the beginning and end of the development of distant metastasis and is implicated in the phenomenon of dormant micrometastases. Antiangiogenic peptides may be altered in the serum or urine of cancer patients. In a study of 144 breast cancer patients, angiogenic protein basic fibroblast growth factor was abnormally elevated in the urine in 29% of cases and in the serum in 10%. Another angiogenic protein, vascular endothelial factor (VEGF), was abnormally elevated in the serum in over 70% of these breast cancer patients (4). Since platelets bind VEGF, platelet values will also be assayed.
HER2-ECD: No data are available regarding the presence of serum HER2-ECD (NRP) levels in c-erbB2 negative tumors, but the extracellular domain of the c-erbB2 oncogene product (NRP) is detectable in sera of 30-60% of patients with cerbB2 positive tumors. Many reports have correlated the elevated serum levels of the cerbB2 with gene amplification and c-erbB2 overexpression in tumor. These data support the hypothesis that the level of NRP protein can reflect the presence of c-erbB2 positive cells and that modification of the factor can predict a decrease of c-erbB2 positive cells during standard adjuvant chemotherapy. Moreover, change in the detectable NRP during the maintenance phase can suggest a possible modification in the biology and/or behaviour of hypothetic micrometastasis.
VCAM-1: In tumors, endothelial VCAM-1 play a major role in the adhesion of leukocytes to the endothelium, suggesting a relationship between cellular adhesion and angiogenesis. Soluble VCAM-1 has been implicated in the mediation of angiogenesis and some studies support the hypothesis that VCAM-1 provides surrogate markers for endothelial activation and angiogenesis occurring during cancers. Recently, VCAM-1 serum levels have been associated with microvessel density and response to endocrine therapy.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Induction chemotherapy | Active comparator | Procedure: Blood samples collectionApproved induction CT regimen after randomization |
| Induction chemotherapy followed by CM maintenance | Experimental | Procedure: Blood samples collectionApproved induction chemotherapy followed by 12 months of CM maintenance |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patient must be randomized to the core protocol. Written informed consent for the serum substudy must be signed and dated by the patient and investigator
- Patient must not have begun CM maintenance (if randomized to CM maintenance)
Key exclusion criteria (2 listed)
- Patient not randomized to the core protocol
- Patient already begun CM maintenance (if randomized to CM maintenance)
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 |
|---|---|---|
| Blood samples collectionBlood samples to be collected at the following time points: 1. Baseline, (after the completion of induction chemotherapy and, if randomized to CM maintenance, before start of CM maintenance.) 2. Months 12, 18 and 36 after start of induction chemotherapy 3. At time of confirmatory evidence of progression | Procedure or surgery | Induction chemotherapy, Induction chemotherapy followed by CM maintenance |
Primary outcome
Change from baseline to 18 months in serum VEGF values
Time frame: 18 months
To evaluate differences from baseline (after completion of induction chemotherapy but before commencement of CM Maintenance for patients randomized to CM Maintenance) to 18 months after the start of induction chemotherapy in serum VEGF values between patients in the Observation Group and those in the low dose Cyclophosphamide Methotrexate (CM) Maintenance Group.
Change from baseline to 18 months in serum VCAM-1 values
Time frame: 18 months
To evaluate differences from baseline (after completion of induction chemotherapy but before commencement of CM Maintenance for patients randomized to CM Maintenance) to 18 months after the start of induction chemotherapy in serum VCAM-1 values between patients in the Observation Group and those in the low dose Cyclophosphamide Methotrexate (CM) Maintenance Group.
Change from baseline to 18 months in serum NRP values
Time frame: 18 months
To evaluate differences from baseline (after completion of induction chemotherapy but before commencement of CM Maintenance for patients randomized to CM Maintenance) to 18 months after the start of induction chemotherapy in serum NRP values between patients in the Observation Group and those in the low dose Cyclophosphamide Methotrexate (CM) Maintenance Group.
6 secondary outcomes
Change from baseline to 12 and 36 months in serum VEGF values
Time frame: 12 & 36 months
Change from baseline to 12 and 36 months in serum VCAM-1 values
Time frame: 12 & 36 months
Change from baseline to 12 and 36 months in serum NRP values
Time frame: 12 & 36 months
Change in serum VEGF values from last measurement before progression to measurement at time of confirmatory evidence of progression
Time frame: Baseline,12-, 18- or 36-months & progression
Change in serum VCAM-1 values from last measurement before progression to measurement at time of confirmatory evidence of progression
Time frame: Baseline,12-, 18- or 36-months & progression
Change in serum NRP values from last measurement before progression to measurement at time of confirmatory evidence of progression
Time frame: Baseline,12-, 18- or 36-months & progression
Results and safety
The study was stopped early (reason given: Sufficient statistical power cannot be met due to low samples size). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2026.
- Background: PubMed 8842493Kern FG, Lippman ME. The role of angiogenic growth factors in breast cancer progression. Cancer Metastasis Rev. 1996 Jun;15(2):213-9. doi: 10.1007/BF00437474. No abstract available.
- Background: PubMed 9059337Gasparini G. Clinical significance of the determination of angiogenesis in human breast cancer: update of the biological background and overview of the Vicenza studies. Eur J Cancer. 1996 Dec;32A(14):2485-93. doi: 10.1016/s0959-8049(96)00376-0. No abstract available.
- Background: PubMed 8664033Revillion F, Hebbar M, Bonneterre J, Peyrat JP. Plasma c-erbB2 concentrations in relation to chemotherapy in breast cancer patients. Eur J Cancer. 1996 Feb;32A(2):231-4. doi: 10.1016/0959-8049(95)00568-4.
- Background: PubMed 10944555Byrne GJ, Ghellal A, Iddon J, Blann AD, Venizelos V, Kumar S, Howell A, Bundred NJ. Serum soluble vascular cell adhesion molecule-1: role as a surrogate marker of angiogenesis. J Natl Cancer Inst. 2000 Aug 16;92(16):1329-36. doi: 10.1093/jnci/92.16.1329.
- SponsorLink provided by the sponsor.
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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.
Aron Goldhirsch, Prof. study chair
IEO Milano
Giuseppe Viale, Prof. study chair
IEO Milano
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Blood samples collection in people with Breast Cancer, run by ETOP IBCSG Partners Foundation at 3 sites in 3 countries.
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 2 inclusion and 2 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: stopped early, as of the sponsor's last update on 12 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Italy, Nigeria, Peru. 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 was stopped early (reason given: Sufficient statistical power cannot be met due to low samples size). Results are not available in the source record.
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?
Change from baseline to 18 months in serum VEGF values (time frame: 18 months). The study lists 3 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 NCT02393833, 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 12 Aug 2026.