B-amyloid as a Marker for GBM Bioimaging

NCT ID: NCT05820191

Last Updated: 2023-12-21

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

NOT_YET_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

3 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-07-31

Study Completion Date

2026-07-31

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.

Conditions

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Glioblastoma

Keywords

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Glioblastoma, Amyvid

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

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.
Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Double blinding analysis of PET images will be performed. Involved Radiologists will provide their independent opinions. In addition, blinding research strategy with withholding of patient information, with three independent people involved for data collection and analysis will be used.

Study Groups

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AMY-GBM

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.

Group Type EXPERIMENTAL

Amyvid, Intravenous Solution

Intervention Type DRUG

Amyvid 370MBq (10mCi) absorbed dose 7mSv of will be introduced intravenously and 30-50 minutes after the PET images will be acquired.

Interventions

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Amyvid, Intravenous Solution

Amyvid 370MBq (10mCi) absorbed dose 7mSv of will be introduced intravenously and 30-50 minutes after the PET images will be acquired.

Intervention Type DRUG

Other Intervention Names

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Florbetapir-f18

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
Minimum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Puerto Rico

OTHER

Sponsor Role collaborator

Universidad Central del Caribe

OTHER

Sponsor Role lead

Responsible Party

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Lilia Kucheryavykh

Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Lilia Kucheryavykh, PhD

Role: PRINCIPAL_INVESTIGATOR

Universidad Central del Caribe (Central University of the Caribbean)

Locations

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Central University of the Caribbean (UCC)

Bayamón, PR, Puerto Rico

Site Status

University of Puerto Rico, Medical Science Campus

San Juan, , Puerto Rico

Site Status

Countries

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Puerto Rico

Central Contacts

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Lilia Kucheryavykh, PhD

Role: CONTACT

Phone: 7877983001

Email: [email protected]

Miguel Mayol Del Valle, MD

Role: CONTACT

Phone: 787-758-2525

Email: [email protected]

Facility Contacts

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Lilia Kucheryavykh, PhD

Role: primary

Miguel Mayol Del Valle, MD

Role: primary

References

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Kucheryavykh LY, Ortiz-Rivera J, Kucheryavykh YV, Zayas-Santiago A, Diaz-Garcia A, Inyushin MY. Accumulation of Innate Amyloid Beta Peptide in Glioblastoma Tumors. Int J Mol Sci. 2019 May 20;20(10):2482. doi: 10.3390/ijms20102482.

Reference Type BACKGROUND
PMID: 31137462 (View on PubMed)

Zayas-Santiago A, Diaz-Garcia A, Nunez-Rodriguez R, Inyushin M. Accumulation of amyloid beta in human glioblastomas. Clin Exp Immunol. 2020 Dec;202(3):325-334. doi: 10.1111/cei.13493. Epub 2020 Aug 11.

Reference Type BACKGROUND
PMID: 32654112 (View on PubMed)

Kucheryavykh LY, Davila-Rodriguez J, Rivera-Aponte DE, Zueva LV, Washington AV, Sanabria P, Inyushin MY. Platelets are responsible for the accumulation of beta-amyloid in blood clots inside and around blood vessels in mouse brain after thrombosis. Brain Res Bull. 2017 Jan;128:98-105. doi: 10.1016/j.brainresbull.2016.11.008. Epub 2016 Nov 28.

Reference Type BACKGROUND
PMID: 27908798 (View on PubMed)

Other Identifiers

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AMY-GBM

Identifier Type: -

Identifier Source: org_study_id