Evaluating Biomarkers of Cognitive Dysfunction in Patients With Cancer

Not yet recruiting

• Conditions: Brain Tumor Adult; Brain Metastases From Solid Tumors; Brain Tumor, Primary; Brain Tumor

• Registration Number: NCT07226466
• Lead Sponsor: University of California, San Francisco

Brief Summary

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.

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 Timeline

• Status Verified: 2025-11
• Study First Submitted: 2025-11-06
• Study First Submitted QC: 2025-11-06
• Last Update Submitted: 2025-11-06
• Study First Posted: 2025-11-10
• Last Update Posted: 2025-11-10
• Study Start: 2026-03-01
• Primary Completion: 2028-05-31
• Study Completion: 2028-05-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 40

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Mean change in serum Phosphorylated TAU (p-TAU)	Up to 12 months	Mean change in biomarker for p-TAU over time will be reported
Mean change in serum Phosphorylated TAU (p-TAU) by APOE genotype	Up to 12 months	Mean change in biomarker for p-TAU by APOE genotype over time will be reported
Mean change in serum Neurofilament Light Chain (NfL)	Up to 12 months	Mean change in biomarker for NfL over time will be reported
Mean change in serum Amyloid-beta peptide (Aβ)	Up to 12 months	Mean change in biomarker for Aβ over time will be reported
Mean change in serum Amyloid-beta peptide (Aβ) by APOE genotype	Up to 12 months	Mean change in biomarker for Aβ by APOE genotype over time will be reported
Mean change of score on the European Organization for Research and Treatment of Cancer quality of life questionnaire - Brain Module (EORTC-QLQ-BN20)	Up to 18 months from date of first radiation dose	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.
Mean change in serum Glial Fibrillary Acidic Protein (GFAP)	Up to 12 months	Mean change in biomarker for GFAP over time will be reported
Mean change in serum Glial Fibrillary Acidic Protein (GFAP) by APOE genotype	Up to 12 months	Mean change in biomarker for GFAP by APOE genotype over time will be reported
Mean change in serum Neurofilament Light Chain (NfL) by APOE genotype	Up to 12 months	Mean change in biomarker for NfL by APOE genotype over time will be reported
Mean change in Brain Health Assessment by APOE genotype	Up to 12 months	Mean change in of Brain Health Assessment by APOE genotype over time will be reported
Mean change in Hippocampal Volume	Up to 12 months	Mean change in Hippocampal Volume as measured by MRI over time will be reported
Mean change in Hippocampal Volume by APOE genotype	Up to 12 months	Mean change in Hippocampal Volume as measured by MRI by APOE genotype over time will be reported

Secondary Outcome Measures

Name	Time	Method
Change in scores on the European Organization for Research and Treatment of Cancer quality of life questionnaire 30 (EORTC-QLQ-C30) over time	Up to 18 months from date of first radiation dose	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.

Trial Locations

Locations (1)

University of California, San Francisco; 🇺🇸 San Francisco, California, United States