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Memory Avoidance Whole Brain Radiotherapy vs Hippocampal Avoidance Whole Brain Radiotherapy (Athena 2 Trial)

Memory Avoidance Whole Brain Radiotherapy vs Hippocampal Avoidance Whole Brain Radiotherapy (Athena 2 Trial)

Recruiting
18 years and older
All
Phase 2

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Overview

Participants in this research study have cancer that has spread to their brain, called brain metastases. One treatment for this type of cancer is called whole brain radiotherapy that stays away from a specific neurocognitive substructure, called the hippocampus, combined with medication to preserve cognitive function. This study compares that approach to another approach of whole brain radiotherapy that stays away from additional structures that are thought to have a role in cognitive function. Researchers want to see if there is a difference in the preservation of cognitive function between these two approaches.

Description

Brain metastases happen when cancer spreads from its original location to the brain. For people with brain metastases, whole brain radiotherapy (WBRT) is important in reducing neurologic symptoms and maximizing intracranial control. Previous studies have shown that adding a drug called memantine to WBRT can help lower the risk of cognitive decline. Previous studies have also shown that hippocampal avoidance WBRT (HA-WBRT) with memantine can reduce the risk of cognitive decline even more. This combination is considered a standard of care option for people with brain metastases.

Even though HA-WBRT successfully reduces the risk of cognitive decline for people with brain metastases, many people still experience some cognitive decline. This means that new treatments are needed to better protect brain function for this population. While avoiding the hippocampus is helpful, there are still many other parts of the brain that may be affected by radiation. Important cognitive structures such as the amygdala, corpus callosum, and fornix are involved with memory processing, executive function, complex task performance, memory formation, and recall. Avoiding these cognitive structures can further preserve cognition for people receiving WBRT.

This study investigates the avoidance of additional cognitive structures (the amygdala, corpus callosum, fornix, hypothalamus, and pituitary) with memory avoidance whole brain radiotherapy (MA-WBRT). The safety and feasibility of MA-WBRT has already been demonstrated. The purpose of this study is to compare MA-WBRT with memantine to HA-WBRT with memantine, which is currently the standard of care for people with extensive brain metastases.

Eligibility

Inclusion Criteria:

  • Participants must have histologically, cytologically, or radiographically confirmed diagnosis of solid tumor with brain metastases
  • Age \>18 years
  • Performance status: Karnofsky Performance Status (KPS) ≥ 70
  • Estimated life expectancy of at least 3 months
  • Participant must be considered a candidate for WBRT by the treating physician
  • Participant must be a primary English speaker and have the ability to understand and the willingness to sign an English written informed consent document
  • Participant has at least 10 brain metastases or is otherwise suitable for WBRT

Exclusion Criteria:

  • Prior whole brain radiation
  • Participant has Multiple Sclerosis, Alzheimer's, dementia, or mental disability
  • Pregnant or breastfeeding women are excluded from this study.
  • Participant is not able to receive an MRI
  • Participant has metastasis within avoidance neurocognitive substructures (hippocampus, amygdala, fornix, corpus callosum, pituitary, amygdala)

Study details
    Brain Metastases

NCT07248228

Case Comprehensive Cancer Center

27 June 2026

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