Clinical trial NCT05820191: B-amyloid as a Marker for GBM Bioimaging
Official title: B-amyloid as a Marker for GBM Bioimaging
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Glioblastoma
Keywords: Glioblastoma, Amyvid
Lead sponsor: Universidad Central del Caribe
Sponsor class: OTHER
Collaborators: name: University of Puerto Rico
First posted: 2023-04-19
Enrollment: 3
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: DIAGNOSTIC

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Measurement of Amyvid deposition in GBM tumor structures
timeFrame: Through study completion, an average of 1 year
measure: Correlation of Amyvid deposition with components of high metabolic activity.
timeFrame: Through study completion, an average of 1 year
measure: Correlation of Amyvid deposition with components of increased vascularization.
timeFrame: Through study completion, an average of 1 year
Secondary outcomes:
measure: Correlation of Amyvid deposition and amyloid- β expression in GBM specimens.
timeFrame: Through study completion, an average of 1 year
measure: Correlation of Amyvid deposition with characteristics of tumor vasculature in GBM specimens.
timeFrame: Through study completion, an average of 1 year
Other outcomes:
Locations:
city: Bayamon
country: Puerto Rico
facility: Central University of the Caribbean (UCC)
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico, Medical Science Campus
Study officials:
affiliation: Universidad Central del Caribe (Central University of the Caribbean)
name: Lilia Kucheryavykh, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.