B-amyloid as a Marker for GBM Bioimaging

Study Overview
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Brief Summary
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This project is aimed at improvement of glioblastoma (GBM) diagnostic strategies for discrimination of tumor progression and chemo- and radiotherapeutic treatment-related changes in brain tissue. The study will elucidate the diagnostic value of PET imaging with use of amyloid-β radioisotope tracer Amyvid (Florbetapir F18) for GBM. The results of the study will provide data for development of new approach for GBM diagnostics.

Detailed Description
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Glioblastoma (GBM) is one of the most malignant forms of brain cancer. Majority of GBMs relapse shortly after tumor resection, and the timely follow-up diagnosis and treatment is vital for patient's survival. However, chemo- and radiotherapeutic treatment of GBM patients cause metabolic and structural changes in brain parenchyma, manifested as metabolic and matrix remodeling modifications, and mimic tumor progression in magnetic resonance imaging (MRI) images. This creates difficulties in discrimination of real tumor progression and post-treatment modifications. No current imaging techniques, including MRI, magnetic resonance spectroscopy (MRS) or perfusion MR (MRP) can provide effective determination of tumor progression and treatment-related changes of brain tissue, that represents current unmet clinical need. The goal of the study is to identify specific biomarker for GBM, that can be used for precise imaging and diagnostics. The accumulation of amyloid-β in human GBM specimens and in mouse glioma implantation model was previously demonstrated. Intravenous administration of amyloid-β marker thioflavin T resulted in accumulation of fluorescence in brain tumors in mouse GBM model 15 minutes after administration and allowed detailed visualization of tumor structure with use of confocal microscopy. The hypothesis of the study is that Amyvid (Florbetapir F18), a radioisotope tracer, that binds amyloid aggregates and is currently used for brain PET diagnostics of Alzheimer disease, can be used as a safe and effective marker for PET diagnostics of recurrent GBM. The central study question: if Amyvid-PET provides visualization of GBM tumors and discriminate recurrent tumor and post-treatment tissue modifications in human brain, and thus presents the potential for amyloid-binding radioisotope tracers as GBM diagnostic tool. The purpose of the study is to characterize and describe the ability of Amyvid to reach GBM tumor in humans and to bind specific tumor structures as necrotic, middle and invasion areas of tumor, as well as blood vessel structures and extracellular matrix in tumor. The study is designed as human clinical trials phase 2A.

Official Title
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B-amyloid as a Marker for GBM Bioimaging

Conditions
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Glioblastoma

Intervention / Treatment
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* Drug: Amyvid, Intravenous Solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: GBM diagnose confirmed by MRI and histopathology Had undergone gross total or subtotal resection of their tumor and developed enlarging and/or new enhancing lesion(s), recommended for second resection Had or had not received radiation therapy with concomitant and adjuvant TMZ chemotherapy Had pre-operative and follow up conventional MRI, MRS and/or Perfusion MR scans, available for analysis Exclusion Criteria: • Previous allergic reaction to radioisotope tracers

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: 3 patients, diagnosed with GBM, who underwent tumor resection surgery with concurrent chemo- and/or radiotherapy and developed enlarging tumor lesion, will be involved to the study. PET-CT with use of Amyvid radioisotope tracer will be performed for 3 study participants. Amyvid-PET images will be analyzed together with previously performed MRI, MRS and MRP images, to identify pattern of deposition in tumor and peri-tumoral areas of brain.Tissue specimens, separated from total tumor after planned surgical resection and prior Amyvid-PET analysis, will be analyzed to identify amyloid-β expression level, tumor phenotype and vascularization. Data will be correlated with PET images to determine whether Amyvid-positive patterns represent distinct tumor phenotype.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AMY-GBM<br>Amyvid-PET scan will be performed. According to approved protocol for Alzheimer's disease diagnostics, 370MBq (10mCi) absorbed dose 7mSv of Amyvid will be introduced intravenously and 30-50 minutes after the PET images will be acquired. | Drug: Amyvid, Intravenous Solution<br>* Amyvid 370MBq (10mCi) absorbed dose 7mSv of will be introduced intravenously and 30-50 minutes after the PET images will be acquired.<br>* Other names: Florbetapir-f18;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of Amyvid deposition in GBM tumor structures | The Amyvid patterns of deposition (brightness or darkness patterns) will be analyzed in whole brain, tumor and peri-tumor resection region with and without representation of post-treatment modifications, as compared to MRI scans. | Through study completion, an average of 1 year | 
| Correlation of Amyvid deposition with components of high metabolic activity. | Association of Amyvid deposition patterns with brain tissue components of high and low metabolic activity will be analyzed as compared to MRS images. | Through study completion, an average of 1 year | 
| Correlation of Amyvid deposition with components of increased vascularization. | Association of Amyvid deposition patterns with areas of high and low vascularization will be analyzed as compared to MRP scans. | Through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of Amyvid deposition and amyloid- β expression in GBM specimens. | Tissue specimens, separated from total tumor after planned surgical resection and prior Amyvid-PET analysis, will be analyzed by western blot to quantify amyloid-β expression level and correlate with deposition of Amyvid, as identified by Amyvid-PET. | Through study completion, an average of 1 year | 
| Correlation of Amyvid deposition with characteristics of tumor vasculature in GBM specimens. | Tissue specimens, separated from total tumor after planned surgical resection and prior Amyvid-PET analysis, will be analyzed with use of immunofluorescence imaging of blood vessels to characterize tumor vasculature structure (as capillary density and diameter) and correlate with deposition of Amyvid, as identified by Amyvid-PET. | Through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glioblastoma, Amyvid