Molecular Neuroimaging to Assess the Link Between Neuroinflammation and Cognitive Impairment in Breast Cancer

NCT04364672 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: R20-003
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This clinical study will use the small molecule translocator protein (TSPO) ligand, 18F-labeled DPA-714, to visualize and quantify neuroinflammation in treatment naive women with stage II-III newly diagnosed breast cancer (without brain metastases) prior to starting neoadjuvant chemotherapy treatment (baseline) and within 4 weeks after finishing neoadjuvant chemotherapy (NACT) with at least 2 cycles administered and before surgery. . The TSPO PET and MRI data acquired through this study will be correlated with cognitive test data, clinical data, and genetic testing collected in this study. We will enroll 20 participants in this study (20 participants with breast cancer). Study Aim 1: To examine the association between neuroinflammation and cancer related cognitive impairment (CRCI) in women with breast cancer before and after undergoing chemotherapy treatment. (Hypothesis 1): Treatment-naïve women with Stage II-III breast cancer (without known brain metastases) will experience increased amount of neuroinflammation and greater cognitive decline after completing neodjuvant Chemotherapy Treatment (NACT). (Hypothesis 2): Greater levels of neuroinflammation as measured by the amount and distribution of \[18F\]DPA-714 in the brain using PET/MRI after completing NACT will be associated with lower levels of cognitive functioning as measured by self-report and/or objective cognitive impairment/change. Neuroinflammation will be measured using PET with tracer \[18F\]DPA-714 using a simultaneous PET/MRI system, and cognitive functioning will be measured with self-report and objective neuropsychological measures. Exploratory Aim 2: To investigate the relationships between CRCI and quality of life (QOL) and everyday functioning in breast cancer survivors after completing chemotherapy treatment. For this Aim, we will assess QOL using self-report measures.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Measure regional brain TSPO levels using [F-18]DPA-714-PET before and after neoadjuvant chemotherapy

  Levels will be presented with mean and 95% CI in the Freesurfer regions of interest (ROI), including cerebellum, hippocampus, amygdala, three white matter regions (frontal, parietal, and occipital), and three cortical gray matter regions (frontal, parietal, and occipital), by combining the corresponding sub-regions provided by Freesurfer.

  Pre-study visit through completion of neoadjuvant chemotherapy (NACT) (Usually around 12 weeks)

Study Arms (1)

Women with stage 1-4 newly diagnosed breast cancer

EXPERIMENTAL

Drug: 18F-labeled DPA-714 PET scan

Interventions

18F-labeled DPA-714 PET scan DRUG

One PET with \[18F\]DPA-714 before chemotherapy treatment begins. One more PET with \[18F\]DPA-714 within 4 weeks after completing NACT including at least 2 cycles administered; before surgery

Women with stage 1-4 newly diagnosed breast cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age or older
• Female gender
• Newly diagnosed treatment naïve women with stage II-III breast cancer that meet the following
• Stage IIA: Any 1 of these conditions:
• There is no evidence of a tumor in the breast, but the cancer has spread to 1 to 3 axillary lymph nodes. It has not spread to distant parts of the body. (T0, N1, M0)
• The tumor is 20 mm or smaller and has spread to the axillary lymph nodes (T1, N1, M0)
• The tumor is larger than 20 mm but not larger than 50 mm and has not spread to the axillary lymph nodes (T2, N0, M0)
• Stage IIb: Either of these conditions
• The tumor is larger than 20 mm but not larger than 50 mm and has spread to 1 to 3 axillary lymph nodes (T2, N1, M0)
• The tumor is larger than 50 mm but has not spread to the axillary lymph nodes (T3, N0, M0)
• Stage IIIA: The cancer of any size has spread to 4 to 9 axillary lymph nodes or to internal mammary lymph nodes. It has not spread to other parts of the body (T0, T1, T2, or T3, N2, M0. Stage IIIA may also be a tumor larger than 50 mm that has spread to 1 to 3 axillary lymph nodes (T3, N1, M0)
• English is the primary language
• Planned neoadjuvant chemotherapy that includes a taxane and/or an anthracycline drug as part of the treatment regimen.

You may not qualify if:

• Contraindications to PET/MRI, including claustrophobia
• Low-affinity binder for TSPO ligands when genotyping is available prior to PET imaging
• Pregnancy
• Lactation
• Individuals who are unable to participate in the imaging portion due to the severity of their medical condition
• Chronic infectious disease (e.g., HIV, HCV)
• Chronic inflammatory disease (e.g., fibromyalgia, MS, etc) or autoimmune disease
• Viral or bacterial illness requiring medical attention and/or antibiotics within 1 month of study participation
• Blood or blood clotting disorder
• Cancer that has metastasized to the brain
• Positive urine β-hCG test day of the procedure or a serum-hCG test within 48 hours prior to the administration of \[18F\]DPA-714
• Currently enrolled in a clinical trial utilizing experimental therapies.
• Prior brain tumor or other neurological condition known to affect cognition
• A diagnosis of dementia unrelated to cancer

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D. P.h.D., Director for the Division Molecular Imaging and Therapeutics

Study Record Dates

• First Submitted: March 2, 2020
• First Posted: April 28, 2020
• Study Start: June 1, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: November 4, 2024

Record last verified: 2024-11