NCT07248228

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

A Randomized Phase 2 Trial of Memory Avoidance Whole Brain Radiotherapy Versus Hippocampal Avoidance Whole Brain Radiotherapy (Athena 2 Trial)

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 90 (estimated)
• Sponsor: Case Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed 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.

Conditions

• Brain Metastases

Interventions

Type	Name	Description
RADIATION	MA-WBRT (Memory Avoidance Whole Brain Radiation Therapy (MA-WBRT))	Participants will receive 10 daily fractions of WBRT per standard of care. Participants receiving MA-WBRT will receive WBRT that avoids the hippocampus, the amygdala, corpus callosum, fornix, hypothalamus, and pituitary.
RADIATION	HA-WBRT (Hippocampal Avoidance Whole Brain Radiation Therapy (HA-WBRT))	Participants will receive 10 daily fractions of WBRT per standard of care. Participants receiving HA-WBRT will receive WBRT that avoids the hippocampus.
DRUG	Memantine	Memantine is prescribed per standard of care. Participants will continue on memantine for 24 weeks. The target dose for memantine is 20 mg (10 mg divided twice daily). Dose is escalated by 5 mg per week to target of 10 mg twice daily (i.e., 5 mg a day for week 1, then 5 mg twice daily for week 2, then 10 mg in the morning and 5 mg in the evening for week 3, then 10 mg in the morning and 10 mg in the evening by week 4). Participants will also be prescribed extended release memantine. The target dose for extended release memantine is 28 mg. Dose is escalated by 7 mg per week to target of 28 mg daily (i.e., 7 mg a day for week 1, then 14 mg a day for week 2, then 21 mg a day for week 3, then 28 mg a day for by week 4).

Timeline

• Start date: 2026-05-01
• Primary completion: 2027-05-01
• Completion: 2028-11-01
• First posted: 2025-11-25
• Last updated: 2026-04-08

Locations

1 site across 1 country: United States