IBCSG Trial 22-00 Serum Substudy

NCT ID: NCT02393833

Last Updated: 2021-05-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

136 participants

Study Classification

INTERVENTIONAL

Study Start Date

2002-06-30

Study Completion Date

2018-03-06

Brief Summary

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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

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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

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Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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Induction chemotherapy

Approved induction CT regimen after randomization

Group Type ACTIVE_COMPARATOR

Blood samples collection

Intervention Type PROCEDURE

Blood 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

Induction chemotherapy followed by CM maintenance

Approved induction chemotherapy followed by 12 months of CM maintenance

Group Type EXPERIMENTAL

Blood samples collection

Intervention Type PROCEDURE

Blood 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

Interventions

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Blood samples collection

Blood 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

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* 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)

Exclusion Criteria

* Patient not randomized to the core protocol
* Patient already begun CM maintenance (if randomized to CM maintenance)
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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ETOP IBCSG Partners Foundation

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Aron Goldhirsch, Prof.

Role: STUDY_CHAIR

IEO Milano

Giuseppe Viale, Prof.

Role: STUDY_CHAIR

IEO Milano

Locations

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Istituto Europeo di Oncologia (IEO

Milan, , Italy

Site Status

Ibadan, , Nigeria

Site Status

Lima, , Peru

Site Status

Countries

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Italy Nigeria Peru

References

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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.

Reference Type BACKGROUND
PMID: 8842493 (View on PubMed)

Gasparini 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.

Reference Type BACKGROUND
PMID: 9059337 (View on PubMed)

Revillion 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.

Reference Type BACKGROUND
PMID: 8664033 (View on PubMed)

Byrne 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.

Reference Type BACKGROUND
PMID: 10944555 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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2005-005666-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

IBCSG 22-00

Identifier Type: OTHER

Identifier Source: secondary_id

IBCSG 22-00 Serum Substudy

Identifier Type: -

Identifier Source: org_study_id

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