Breast CancerPhase 2NCT02317783
Amyloid Plaque Deposition in Chemotherapy-Induced Cognitive Impairment
A Phase 2 study testing [18F]Flutemetamol, [18F]fluoro-2-deoxy-D-glucose (FDG) and Functional Magnetic Resonance Imaging (fMRI) in people with Breast Cancer, run by University of Utah at 1 site in United States.
Trial summary
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)… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- [18F]Flutemetamol, [18F]fluoro-2-deoxy-D-glucose (FDG) and Functional Magnetic Resonance Imaging (fMRI)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Jan 2018to 24 Sep 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female patients must be 18 years or older for inclusion in this research study. There is inadequate experience with the safety of Flutemetamol in children and therefore this radiopharmaceutical should not be used in patients under the age of 18. Individuals over 70 years age will be excluded as the incidence of amyloid positivity increases significantly even with no cognitive problems and will not allow for testing of our primary hypothesis.
- The patient must have a histologically proven diagnosis of Stage I through IIIC Breast Cancer.
- The patient must have completed adjuvant chemotherapy within at least 6 months, but no more than 36 months prior to initial study scan.
- The patient must report persistent cognitive problems, defined as being one or more standard deviations above normative data on our two scales of subjective cognitive dysfunction. This is defined as a total score of 45 or higher on the Cognitive Failure Questionnaire, and a T-score of 60 or higher on the Frontal System Behavioral Scale Questionnaire.
- Patients must agree to have clinical and radiographic endpoints and the results of histopathologic tissue analysis and other laboratory information entered into a research database, as evidenced by signing the informed consent form.
- All patients, or their legal guardians, must sign a written informed consent and HIPAA authorization in accordance with institutional guidelines.
Who cannot join
- Patients with known allergic or hypersensitivity reactions to previously administered radiopharmaceuticals. Patients with significant drug or other allergies or autoimmune diseases may be enrolled at the Investigator's discretion.
- Adult patients who require monitored anesthesia for PET scanning.
- Patients who are too claustrophobic to undergo MRI or PET imaging.
- History of neurological disease known to affect cognition (e.g., stroke, head injury with loss of consciousness of greater than 30 minutes, seizure disorder, demyelinating disorder, mental retardation, primary brain tumor, brain metastases, etc.)
- Current or past major psychiatric illness (e.g., schizophrenia, bipolar affective disorder)
- Evidence of stroke or mass lesion on CT or MRI scan
Show all 14Show fewer
- History of alcoholism or other substance abuse
- Current use of cholinesterase inhibitors, other cognitive enhancers, antipsychotics, antidepressants, or anticonvulsant medications
- Current use of gabapentin or venlafaxine for hot flashes
- History of radiation therapy to the brain
- Uncontrolled diabetes or blood glucose greater than 175 mg/dl on the day of the FDG-PET scan
- Currently pregnant
- Color blindness (cannot complete D-KEFS Stroop test)
- Moderate or Severe Depression as measured on the Beck Depression Inventory (BDI) -Short Form. The cut-off score for the BDI will be 8/9.
Trial locations and contacts
1 site in 1 country.
United States1 site
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
About this study
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.
Read more
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.
- Conditions
- Breast Cancer
- Being tested
- [18F]Flutemetamol, [18F]fluoro-2-deoxy-D-glucose (FDG), Functional Magnetic Resonance Imaging (fMRI)
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[18F]FlutemetamolDrug
Also called [18F]GE067, Vizamyl, [18F]Flutemetamol-PET/CT
Brain scan with imaging tracer that binds to amyloid plaques
[18F]fluoro-2-deoxy-D-glucose (FDG)Drug
Also called FDG, [18F]FDG, FDG-PET/CT
Brain scan with imaging tracer used for measuring glucose metabolism in the assessment, diagnosis, and staging of patients with cancer
Functional Magnetic Resonance Imaging (fMRI)Diagnostic test
Also called MRI, fMRI
Brain scan to assess regions of abnormal volume and density
| Study group | Role | What they receive |
|---|---|---|
| All Participants | Experimental | All enrolled subjects will complete three imaging sessions on separate days that consist of: 1) [18F]Flutemetamol-PET/CT, 2) FDG-PET/CT, and 3) MRI. The order of the performance of these studies will be based upon subject and radioisotope availability, but they will all be completed within 2 months of each other. Receives: Drug: [18F]Flutemetamol; Drug: [18F]fluoro-2-deoxy-D-glucose (FDG); Diagnostic Test: Functional Magnetic Resonance Imaging (fMRI) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Scans With Abnormal [18F]Flutemetamol Uptake
[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.
Measured: [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.
Secondary outcomes (1)
Number of Scans Positive for [18F]Flutemetamol Uptake
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 generate a Z-score, which is then used to determine a positive or negative scan (Z-score > 2 = Positive, Z-score < 2 = Negative).
Measured: [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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2014 (estimated)
- Study start31 Jan 2018
- Primary completion24 Sep 2019
- Study completion24 Sep 2019
Why it stopped: Enrollment challenges
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by University of UtahThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02317783
- Sponsor's protocol ID
- HCI69515
- Status last verified
- Oct 2024
- First submitted
- 11 Dec 2014
- Last updated
- 20 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Amyloid Plaque Deposition in Chemotherapy-Induced Cognitive Impairment
- ClinicalTrials.gov ID
- NCT02317783
- Acronym / sponsor ID
- HCI69515
- Conditions
- Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Enrollment challenges
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Study start
- 31 Jan 2018 (actual)
- Primary completion
- 24 Sep 2019 (actual)
- Study completion
- 24 Sep 2019 (actual)
- First posted
- 16 Dec 2014 (estimated)
- Results
- Posted 20 Nov 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All Participants | Experimental | Drug: [18F]Flutemetamol, Drug: [18F]fluoro-2-deoxy-D-glucose (FDG), Diagnostic Test: Functional Magnetic Resonance Imaging (fMRI)All enrolled subjects will complete three imaging sessions on separate days that consist of: 1) [18F]Flutemetamol-PET/CT, 2) FDG-PET/CT, and 3) MRI. The order of the performance of these studies will be based upon subject and radioisotope availability, but they will all be completed within 2 months of each other. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Female patients must be 18 years or older for inclusion in this research study. There is inadequate experience with the safety of Flutemetamol in children and therefore this radiopharmaceutical should not be used in patients under the age of 18. Individuals over 70 years age will be excluded as the incidence of amyloid positivity increases significantly even with no cognitive problems and will not allow for testing of our primary hypothesis.
- The patient must have a histologically proven diagnosis of Stage I through IIIC Breast Cancer.
- The patient must have completed adjuvant chemotherapy within at least 6 months, but no more than 36 months prior to initial study scan.
- The patient must report persistent cognitive problems, defined as being one or more standard deviations above normative data on our two scales of subjective cognitive dysfunction. This is defined as a total score of 45 or higher on the Cognitive Failure Questionnaire, and a T-score of 60 or higher on the Frontal System Behavioral Scale Questionnaire.
- Patients must agree to have clinical and radiographic endpoints and the results of histopathologic tissue analysis and other laboratory information entered into a research database, as evidenced by signing the informed consent form.
Key exclusion criteria (14 listed)
- Patients with known allergic or hypersensitivity reactions to previously administered radiopharmaceuticals. Patients with significant drug or other allergies or autoimmune diseases may be enrolled at the Investigator's discretion.
- Adult patients who require monitored anesthesia for PET scanning.
- Patients who are too claustrophobic to undergo MRI or PET imaging.
- History of neurological disease known to affect cognition (e.g., stroke, head injury with loss of consciousness of greater than 30 minutes, seizure disorder, demyelinating disorder, mental retardation, primary brain tumor, brain metastases, etc.)
- Current or past major psychiatric illness (e.g., schizophrenia, bipolar affective disorder)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| [18F]FlutemetamolAlso: [18F]GE067, Vizamyl, [18F]Flutemetamol-PET/CTBrain scan with imaging tracer that binds to amyloid plaques | Drug | All Participants |
| [18F]fluoro-2-deoxy-D-glucose (FDG)Also: FDG, [18F]FDG, FDG-PET/CTBrain scan with imaging tracer used for measuring glucose metabolism in the assessment, diagnosis, and staging of patients with cancer | Drug | All Participants |
| Functional Magnetic Resonance Imaging (fMRI)Also: MRI, fMRIBrain scan to assess regions of abnormal volume and density | Diagnostic test | All Participants |
Primary outcome
Number of Scans With Abnormal [18F]Flutemetamol Uptake
Time frame: [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.
1 secondary outcome
Number of Scans Positive for [18F]Flutemetamol Uptake
Time frame: [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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing [18F]Flutemetamol, [18F]fluoro-2-deoxy-D-glucose (FDG) and Functional Magnetic Resonance Imaging (fMRI) in people with Breast Cancer, run by University of Utah at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Scans With Abnormal [18F]Flutemetamol Uptake (time frame: [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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2024.