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

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.

Study Overview

• Status: Withdrawn
• Conditions: Ovarian Cancer
• Intervention / Treatment: Drug: [11C]PiB and 18F-labeled DPA-714 PET scan

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • The University of Alabama at Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 50 years of age or older
2. Female gender
3. Newly diagnosed treatment naïve women with stage III/IV epithelial ovarian cancer (without known brain metastases).
4. High or mixed affinity binder for TSPO ligands based on genotyping for single nucleotide polymorphism (SNP) rs6971.
5. English is primary language
6. Planned neoadjuvant chemotherapy with platinum and taxane drugs

Exclusion Criteria:

1. Contraindication to MRI
2. Pregnancy
3. Lactation
4. Individuals who are unable to participate in the imaging portion due to severity of their medical condition
5. Chronic infectious disease (e.g. HIV, HCV)
6. Chronic inflammatory disease (e.g., fibromyalgia, MS, etc) or autoimmune disease
7. Viral or bacterial illness requiring medical attention and/or antibiotics within 1 month of study participation
8. Blood or blood clotting disorder
9. Cancer that has metastasized to the brain
10. 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.
11. Currently enrolled in a clinical trial utilizing experimental therapies.
12. Low affinity binder for TSPO ligands based on genotyping for SNP rs6971.
13. Prior brain tumor or other neurological condition known to affect cognition
14. A diagnosis of dementia unrelated to cancer or an adjusted MMSE score < 24

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: treatment naivete women with stage 1-4 newly diagnosed ovarian	Drug: [11C]PiB and 18F-labeled DPA-714 PET scan; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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)

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Investigators: Principal Investigator: Jonathan McConathy, MD, PhD, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: August 13, 2020
• First Submitted That Met QC Criteria: September 2, 2020
• First Posted (Actual): September 9, 2020

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Inflammation; Genital Neoplasms, Female; Neurocognitive Disorders; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Cognition Disorders; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Ovarian Neoplasms; Cognitive Dysfunction; Carcinoma, Ovarian Epithelial; Neuroinflammatory Diseases
• Other Study ID Numbers: R20-100

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: To be determined

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No