NCT02317783

Amyloid Plaque Deposition in Chemotherapy-Induced Cognitive Impairment

Terminated Phase 2 Results posted Last updated 20 November 2024

What this trial tests

Phase 2 trial testing [18F]Flutemetamol in Breast Cancer in 15 participants. Terminated before completion.

Timeline

31 January 2018

Primary endpoint
24 September 2019

24 September 2019

Quick facts

Lead sponsor	University of Utah
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	diagnostic
Enrollment	15
Start date	31 January 2018
Primary completion	24 September 2019
Estimated completion	24 September 2019
Sites	1 location across United States

Drugs / interventions tested

• [18F]Flutemetamol
• [18F]fluoro-2-deoxy-D-glucose (FDG) — full drug profile →
• Functional Magnetic Resonance Imaging (fMRI)

Conditions studied

• Breast Cancer — all drugs for Breast Cancer →

Sponsor

University of Utah

Who can join

18 and older, female only, with Breast Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Scans With Abnormal [18F]Flutemetamol Uptake Primary · [18F]Flutemetamol-PET/CT scans were acquired within 30 days of confirmed cognitive impairment via neuropsychological testing. Images were reviewed following completion of all study procedures.

\[18F\]Flutemetamol uptake will be assessed by visual criteria according to the approved Vizamyl prescribing information. Scans will be assessed by a binary grade of positive or negative corresponding to abnormal \[18F\]Flutemetamol uptake.

Group	Value	95% CI
All Participants	0

Number of Scans Positive for [18F]Flutemetamol Uptake Secondary · [18F]Flutemetamol-PET/CT scans were acquired within 30 days of confirmed cognitive impairment via neuropsychological testing. Evaluation of [18F]Flutemetamol binding was performed following completion of all study procedures.

Scans will be evaluated for positive \[18F\]Flutemetamol binding using a semi-quantitative technique performed by CortexID Suite, a software application provided by GE Healthcare. A standardized uptake value ratio (SUVR) is computed by normalizing regional uptake to the cerebellum or pons. The software averages the SUVR \[18F\]Flutemetamol uptake from the following regions to yield a global composite: lateral frontal, lateral temporal, lateral parietal, anterior cingulate, and posterior cingulate. This composite score is compared to the scan data from age- and sex-matched healthy controls to g

Group	Value	95% CI
All Participants	0

Sponsor's own description

The initial goal of the investigators interdisciplinary group of imagers, oncologists, neurologists, neuro-psychologists, and biostatisticians is to obtain proof of concept pilot data for eventual submission of a National Cancer Institute Quick-Trial for Imaging and Image-Guided Interventions: Exploratory Grant (R10) depending on the results of this pilot study.

The overall objective is to use \[18F\]Flutemetamol, FDG-PET, and fMRI to better understand CICI, which effects up to 16 -50% of individuals receiving long-term adjuvant chemotherapy.2,3 To date there have been few studies examining this problem using multi-modality imaging techniques to better understand this complex and significant problem.

FDG-PET and fMRI are routinely used in clinical practice for the evaluation of cognitive dysfunction in older populations complaining of memory dysfunction. It is well recognized that FDG-PET can assist with the differentiation and characterization of various cognitive disorders due to unique patterns of cerebral metabolism caused by various cognitive and dementia-causing disorders.4-6 FDG-PET has been studied extensively in dementia research and has a high reliability in detecting Alzheimers disease (AD) many years before it can be diagnosed reliably using clinical criteria.4

To the investigators knowledge, there has been only a single small study using FDG-PET and bolus water activation paradigms in cancer patients complaining of memory problems.7 To date, there have been no studies using \[18F\]Flutemetamol as a PET imaging agent to assess the possibility of increased amyloid plaque burden as a potential contributing factor to the cognitive deficits and complaints seen in patients experiencing CICI. The novel feature of this project is in the combined use of \[18F\]Flutemetamol-PET, FDG-PET, and fMRI to study a poorly understood but common problem: cognitive impairment in breast cancer patients treated with chemotherapy.

If \[18F\]Flutemetamol, FDG-PET, and fMRI can provide information on the pathophysiology of this disorder, it will be an important step in better understanding the etiology of this phenomenon and possibly other conditions resulting in cognitive dysfunction. These imaging assessments will make it possible to explore any altered changes in cerebral structure, metabolism, and amyloid deposition that may be responsible for CICI. This may help to predict which individuals may be affected by this problem and provide information for eventual therapeutic strategies to treat this common cancer-associated disorder.

This study will use \[18F\]Flutemetamol and FDG-PET imaging to assess and quantify the amyloid plaque burden and cerebral glucose metabolism, respectively, in breast cancer patients suffering from CICI and correlate those findings with structural changes on MRI. The \[18F\]Flutemetamol and FDG-PET scans of these study patients will then be compared to two GE software databases (CortexID-FDG and CortexID-Flutemetamol) which contain scan data from healthy control individuals to evaluate for abnormalities in cerebral glucose metabolism and amyloid plaque burden differing from the values expected for individuals in their age range.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Application of PET Tracers in Molecular Imaging for Breast Cancer.
   Boers J, de Vries EFJ, Glaudemans AWJM, Hospers GAP, et al · · 2020 · cited 25× · PMID 32627087 · DOI 10.1007/s11912-020-00940-9