Evaluating Biomarkers of Cognitive Dysfunction in Patients With Cancer

This study investigates the effects of brain radiotherapy on cognitive function by evaluating plasma biomarkers and apolipoprotein E (APOE) genotype in patients with primary or metastatic brain tumors. Standard brain radiotherapy is known to impact cognitive outcomes, yet the underlying biological mechanisms remain unclear.

Study Overview

• Status: Not yet recruiting
• Conditions: Brain Tumor; Brain Tumor, Primary; Brain Tumor Adult; Brain Metastases From Solid Tumors
• Intervention / Treatment: Procedure: Blood sample; Procedure: Brain magnetic resonance imaging (MRI); Procedure: Brain Health Assessment; Radiation: Quality of Life (QoL) Questionnaire

Detailed Description

PRIMARY OBJECTIVES:

1. Assess plasma biomarkers for Aβ, GFAP, phospho Tau, and NfL pre- and post-radiotherapy.
2. Determine APOE genotype.
3. Evaluate neuropsychiatric testing aligned with standard of care brain MRIs and serum markers.
4. Measure brain morphometrics pre- and post-radiotherapy with standard of care brain MRIs.

SECONDARY OBJECTIVES:

1. Measure patient-reported quality of life changes pre- and post-radiotherapy using a standard University of California, San Francisco (UCSF) -approved questionnaire.

OUTLINE:

This is a single-arm, non-randomized, open-label pilot study. Participants will be study duration spans 12 months post-brain radiotherapy.

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Jean Nakamura, MD; Phone Number: (415) 514-4997; Email: Jean.Nakamura@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
      • Contact: Jean Nakamura, MD; Phone Number: 877-827-3222; Email: cancertrials@ucsf.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult participants with brain cancers receiving care at University of California, San Francisco (UCSF)

Description

Inclusion Criteria:

1. >= 18 years old
2. Diagnosis of a primary brain tumor OR #3. Not both #2 and #3.
3. Diagnosis of primary solid tumor and secondary involvement of the brain
4. If the patient has brain metastases: fewer than 5 brain metastases (post-operative and definitive allowed), none > 1 cm in max diameter.
5. Candidate for standard of care / usual care (SOC) focused brain radiotherapy.
6. No prior brain radiotherapy, including whole brain radiotherapy.
7. Eastern Cooperative Oncology Group (ECOG) functional score 0 or 1.
8. Estimated life expectancy post-treatment of > 2 years.

Exclusion Criteria:

1. Diagnosis of neurodegenerative disease (Alzheimer's disease, Parkinson's disease).
2. Diagnosis of memory disorder pre-treatment.
3. Leptomeningeal disease or disease involving either hippocampus.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Adults with Brain Tumor Receiving Radiotherapy; The study entails longitudinal assessment of plasma biomarkers (Aβ, GFAP, phospho Tau, NfL), determination of APOE genotype, neuropsychiatric testing Brain Health Assessment test (BHA), a clinically validated neurocognitive battery compiling metrics on memory and language), and brain morphometric measurements synchronized with standard of care brain MRIs.

Procedure: Blood sample; Blood sample will be collected; Procedure: Brain magnetic resonance imaging (MRI); Brain MRI will be performed during the course of data collection; Procedure: Brain Health Assessment; Brain Health Assessment will be performed during the course of data collection; Radiation: Quality of Life (QoL) Questionnaire; QoL questionnaire will be given to participants during the course of data collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change in serum Amyloid-beta peptide (Aβ)	Mean change in biomarker for Aβ over time will be reported	Up to 12 months
Mean change in serum Amyloid-beta peptide (Aβ) by APOE genotype	Mean change in biomarker for Aβ by APOE genotype over time will be reported	Up to 12 months
Mean change of score on the European Organization for Research and Treatment of Cancer quality of life questionnaire - Brain Module (EORTC-QLQ-BN20)	The EORTC QLQ-BN20 consists of 20 questions; seven single item symptom scales (headaches, seizures, drowsiness, hair loss, itchy skin, leg weakness and bladder control), along with four multi-item scales (future uncertainty, visual disorder, motor dysfunction and communication deficit). Raw scores for the QLQ-BN20 items are computed by calculating the mean of the items in each subscale, or the item for each individual and linearly transform the scores to a 0-100 scale. A higher score represents worse QOL for all QLQ-BN20 scales and single items.	Up to 18 months from date of first radiation dose
Mean change in serum Glial Fibrillary Acidic Protein (GFAP)	Mean change in biomarker for GFAP over time will be reported	Up to 12 months
Mean change in serum Glial Fibrillary Acidic Protein (GFAP) by APOE genotype	Mean change in biomarker for GFAP by APOE genotype over time will be reported	Up to 12 months
Mean change in serum Phosphorylated TAU (p-TAU)	Mean change in biomarker for p-TAU over time will be reported	Up to 12 months
Mean change in serum Phosphorylated TAU (p-TAU) by APOE genotype	Mean change in biomarker for p-TAU by APOE genotype over time will be reported	Up to 12 months
Mean change in serum Neurofilament Light Chain (NfL)	Mean change in biomarker for NfL over time will be reported	Up to 12 months
Mean change in serum Neurofilament Light Chain (NfL) by APOE genotype	Mean change in biomarker for NfL by APOE genotype over time will be reported	Up to 12 months
Mean change in Brain Health Assessment by APOE genotype	Mean change in of Brain Health Assessment by APOE genotype over time will be reported	Up to 12 months
Mean change in Hippocampal Volume	Mean change in Hippocampal Volume as measured by MRI over time will be reported	Up to 12 months
Mean change in Hippocampal Volume by APOE genotype	Mean change in Hippocampal Volume as measured by MRI by APOE genotype over time will be reported	Up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in scores on the European Organization for Research and Treatment of Cancer quality of life questionnaire 30 (EORTC-QLQ-C30) over time	The functional domains measure the quality of life in Physical functioning, Role functioning, Emotional functioning, Cognitive functioning, Social functioning. Scores consists of responses to items with responses ranging from 1="Not at all" to 4="Very Much". The raw score is calculated by estimating the mean of the items that make up each domains with a resulting total range of 1 - 4. These scores are then transformed to standardized scale score, so that scores range from 0 to 100. A high score for the functional domains represents a high level of functioning.	Up to 18 months from date of first radiation dose

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Investigators: Principal Investigator: Jean Nakamura, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): October 31, 2028
• Study Completion (Estimated): October 31, 2028

Study Registration Dates

• First Submitted: November 6, 2025
• First Submitted That Met QC Criteria: November 6, 2025
• First Posted (Actual): November 10, 2025

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Brain Neoplasms; Health Care Quality, Access, and Evaluation; Investigative Techniques; Epidemiologic Methods; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Data Collection; Health Care Evaluation Mechanisms; Quality of Health Care; Public Health; Environment and Public Health; Health Status; Demography; Epidemiologic Measurements; Surveys and Questionnaires; Quality of Life; Blood Specimen Collection
• Other Study ID Numbers: 249213; NCI-2025-01532 (Registry Identifier: NCI Clinical Trials Reporting Program (CTRP))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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