Neuroinflammation and Age-associated Brain Pathology: Two Potential Mechanisms of Cognitive Impairment in Ovarian Cancer

Study Overview
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Brief Summary
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This clinical study will use the small molecule translocator protein (TSPO) ligand, 18F-labeled DPA- 714, to visualize and quantify neuroinflammation in treatment naivete women with stage 1-4 newly diagnosed ovarian cancer (without brain metastases) prior to starting neoadjuvant chemotherapy treatment (baseline) and within a month of completing first 6 cycles of cytotoxic chemotherapy treatment (follow-up). In addition, we will use the well-characterized small molecule PET(Positron Emission Tomography) tracer, 11C-labeled Pittsburgh compound B (PiB) to visualize and quantify the regional brain distribution of pathological amyloid deposition at baseline only. The brain amyloid PET and MRI data acquired through this study will be correlated with cognitive test data, clinical data, genetic testing, and biospecimens collected in this study.

Official Title
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Neuroinflammation and Age-associated Brain Pathology: Two Potential Mechanisms of Cognitive Impairment in Ovarian Cancer

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Drug: [11C]PiB and 18F-labeled DPA-714 PET scan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 50 years of age or older Female gender Newly diagnosed treatment naïve women with stage III/IV epithelial ovarian cancer (without known brain metastases). High or mixed affinity binder for TSPO ligands based on genotyping for single nucleotide polymorphism (SNP) rs6971. English is primary language Planned neoadjuvant chemotherapy with platinum and taxane drugs Exclusion Criteria: Contraindication to MRI Pregnancy Lactation Individuals who are unable to participate in the imaging portion due to 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 hCG test day of procedure or a serum hCG test within 48 hours prior to the administration of [18F]DPA-714 and [11C]PiB. Currently enrolled in a clinical trial utilizing experimental therapies. Low affinity binder for TSPO ligands based on genotyping for SNP rs6971. Prior brain tumor or other neurological condition known to affect cognition A diagnosis of dementia unrelated to cancer or an adjusted MMSE score < 24

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment naivete women with stage 1-4 newly diagnosed ovarian<br> | Drug: [11C]PiB and 18F-labeled DPA-714 PET scan<br>* One PET with [11C]PiB and One PET with [18F]DPA-714 before chemotherapy treatment begins. One more PET with [18F]DPA-714 after completion of 3-6 cycles of chemotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure neuroinflammation by calculating the concentration and regional distribution of activated brain microglia/macrophages using the PET ligand [F-18]DPA-714. |  | Pre-study visit through 3-6 cycles of chemotherapy (each cycle is typically 2 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlate cognitive impairment before and after beginning cancer therapy with the concentration and regional brain distribution of pathologic amyloid deposition measured with the PET tracer [C-11]PiB prior to beginning therapy. |  | Pre-study visit through 3-6 cycles of chemotherapy (each cycle is typically 2 weeks) |