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Memory Avoidance vs. Hippocampal Avoidance Whole Brain Radiotherapy for Brain Metastases

This study is for people with cancer that has spread to their brain (brain metastases). It compares two types of whole brain radiation therapy (WBRT) given with the drug Memantine. One type, called Hippocampal Avoidance WBRT (HA-WBRT), avoids the hippocampus, a part of the brain important for memory. The other type, Memory Avoidance WBRT (MA-WBRT), avoids the hippocampus plus other brain areas involved in memory and thinking. Researchers want to see if MA-WBRT better protects your thinking and memory skills compared to HA-WBRT. You may be able to join if you are over 18, have brain metastases, and are considered a candidate for WBRT. The study aims to see how long it takes for thinking and memory problems to develop.

Study design
This interventional study plans to enroll 90 participants. It compares two different radiation therapy approaches.
What's involved
Participants will receive 10 daily fractions of WBRT and take Memantine for 24 weeks. Thinking and memory tests will be done at the start and at 3 months.
Compensation
Not stated in the trial record.
Follow-up
Your thinking and memory will be monitored for up to 12 months.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT07248228

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

Recruiting
PHASE2Ages 18+InterventionalSupportive care
Case Comprehensive Cancer Center
~90 participants
Updated 2026-08-06 on ClinicalTrials.gov
What's tested:MA-WBRT (Memory Avoidance Whole Brain Radiation Therapy (MA-WBRT))HA-WBRT (Hippocampal Avoidance Whole Brain Radiation Therapy (HA-WBRT))Memantine

At a glance

Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Time to neurocognitive failure (NCF)
Measured over Up to 12 months
+20 more outcomes measured

Conditions

Brain Metastases

Explore related trials

Metastatic Malignant Neoplasm in the BrainSolid Neoplasm

Where it's being run

1 sites across 1 states
Ohio1

Study leadership

  • Haley Perlow, MD · PRINCIPAL_INVESTIGATOR · Case Comprehensive Cancer Center, University Hospitals

Who to contact

Haley Perlow, MD
[email protected]
(216) 286-3906
Email the study team

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Do you actually qualify for this trial?

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Eligibility criteria

Inclusion

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

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)

What this trial measures

  • Time to neurocognitive failure (NCF)Up to 12 months

    Time to NCF is defined as cognitive decline on the reliable change index (RCI) on at least one of the following tests: HVLT-R, TMT A/B, COWAT, BVMT-R. Tests are defined below.

  • Hopkins Verbal Learning Test-Revised (HVLT-R)Day 1 (prior to WBRT treatment)

    The HVLT-R involves three learning trials: Total Recall, Delayed Recall, and Delayed Recognition. The HVLT-R is administered by the examiner reading a 12-item list of words and asking the participant to recall as many as possible (Total Recall). After a 20-25 minutes interval of unrelated tasks, the examiner asks the participant to recall as many words as possible from the original list (Delayed Recall). Then, the examiner reads a 24-item list of words, where 12 words were on the original list and 12 were not (Delayed Recognition). The examiner asks the participant to respond "yes" if the word was on the original list or "no" if it was not. The HVLT-R is scored by summing the number of correctly recalled words across the three trials. Higher scores indicate greater recall.

  • Hopkins Verbal Learning Test-Revised (HVLT-R)Month 3

    The HVLT-R involves three learning trials: Total Recall, Delayed Recall, and Delayed Recognition. The HVLT-R is administered by the examiner reading a 12-item list of words and asking the participant to recall as many as possible (Total Recall). After a 20-25 minutes interval of unrelated tasks, the examiner asks the participant to recall as many words as possible from the original list (Delayed Recall). Then, the examiner reads a 24-item list of words, where 12 words were on the original list and 12 were not (Delayed Recognition). The examiner asks the participant to respond "yes" if the word was on the original list or "no" if it was not. The HVLT-R is scored by summing the number of correctly recalled words across the three trials. Higher scores indicate greater recall.

  • Hopkins Verbal Learning Test-Revised (HVLT-R)Month 6

    The HVLT-R involves three learning trials: Total Recall, Delayed Recall, and Delayed Recognition. The HVLT-R is administered by the examiner reading a 12-item list of words and asking the participant to recall as many as possible (Total Recall). After a 20-25 minutes interval of unrelated tasks, the examiner asks the participant to recall as many words as possible from the original list (Delayed Recall). Then, the examiner reads a 24-item list of words, where 12 words were on the original list and 12 were not (Delayed Recognition). The examiner asks the participant to respond "yes" if the word was on the original list or "no" if it was not. The HVLT-R is scored by summing the number of correctly recalled words across the three trials. Higher scores indicate greater recall.

  • Hopkins Verbal Learning Test-Revised (HVLT-R)Month 9

    The HVLT-R involves three learning trials: Total Recall, Delayed Recall, and Delayed Recognition. The HVLT-R is administered by the examiner reading a 12-item list of words and asking the participant to recall as many as possible (Total Recall). After a 20-25 minutes interval of unrelated tasks, the examiner asks the participant to recall as many words as possible from the original list (Delayed Recall). Then, the examiner reads a 24-item list of words, where 12 words were on the original list and 12 were not (Delayed Recognition). The examiner asks the participant to respond "yes" if the word was on the original list or "no" if it was not. The HVLT-R is scored by summing the number of correctly recalled words across the three trials. Higher scores indicate greater recall.

  • Hopkins Verbal Learning Test-Revised (HVLT-R)Month 12

    The HVLT-R involves three learning trials: Total Recall, Delayed Recall, and Delayed Recognition. The HVLT-R is administered by the examiner reading a 12-item list of words and asking the participant to recall as many as possible (Total Recall). After a 20-25 minutes interval of unrelated tasks, the examiner asks the participant to recall as many words as possible from the original list (Delayed Recall). Then, the examiner reads a 24-item list of words, where 12 words were on the original list and 12 were not (Delayed Recognition). The examiner asks the participant to respond "yes" if the word was on the original list or "no" if it was not. The HVLT-R is scored by summing the number of correctly recalled words across the three trials. Higher scores indicate greater recall.

  • Controlled Oral Word Association Test (COWAT)Day 1 (prior to WBRT treatment)

    The COWAT is a verbal fluency test that involves the examiner asking the participant to name as many words as they can that start with a designated letter, excluding proper nouns, for one minute. This is repeated three times. The examiner records the words provided by the participant, and the COWAT is scored by calculating the total number of acceptable words that the participant produced. Greater scores indicate a higher performance (greater cognitive capabilities) on the test.

  • Controlled Oral Word Association Test (COWAT)Month 3

    The COWAT is a verbal fluency test that involves the examiner asking the participant to name as many words as they can that start with a designated letter, excluding proper nouns, for one minute. This is repeated three times. The examiner records the words provided by the participant, and the COWAT is scored by calculating the total number of acceptable words that the participant produced. Greater scores indicate a higher performance (greater cognitive capabilities) on the test.

  • Controlled Oral Word Association Test (COWAT)Month 6

    The COWAT is a verbal fluency test that involves the examiner asking the participant to name as many words as they can that start with a designated letter, excluding proper nouns, for one minute. This is repeated three times. The examiner records the words provided by the participant, and the COWAT is scored by calculating the total number of acceptable words that the participant produced. Greater scores indicate a higher performance (greater cognitive capabilities) on the test.

  • Controlled Oral Word Association Test (COWAT)Month 9

    The COWAT is a verbal fluency test that involves the examiner asking the participant to name as many words as they can that start with a designated letter, excluding proper nouns, for one minute. This is repeated three times. The examiner records the words provided by the participant, and the COWAT is scored by calculating the total number of acceptable words that the participant produced. Greater scores indicate a higher performance (greater cognitive capabilities) on the test.

  • Controlled Oral Word Association Test (COWAT)Month 12

    The COWAT is a verbal fluency test that involves the examiner asking the participant to name as many words as they can that start with a designated letter, excluding proper nouns, for one minute. This is repeated three times. The examiner records the words provided by the participant, and the COWAT is scored by calculating the total number of acceptable words that the participant produced. Greater scores indicate a higher performance (greater cognitive capabilities) on the test.

  • Brief Visuospatial Memory Test-Revised (BVMT-R)Day 1 (prior to WBRT treatment)

    The BVMT-R test involves a participant viewing a page of six figures for 10 seconds and then being asked to draw as many figures as they can remember in their correct places. This is repeated three times. Then, after a 25 minute interval, the examiner asks the participant to recall and draw the figures again. The BVMT-R is scored by summing how many items the participant correctly recalled for each trial. Higher scores indicate higher performance (greater cognitive capabilities) on the test.

  • Brief Visuospatial Memory Test-Revised (BVMT-R)Month 3

    The BVMT-R test involves a participant viewing a page of six figures for 10 seconds and then being asked to draw as many figures as they can remember in their correct places. This is repeated three times. Then, after a 25 minute interval, the examiner asks the participant to recall and draw the figures again. The BVMT-R is scored by summing how many items the participant correctly recalled for each trial. Higher scores indicate higher performance (greater cognitive capabilities) on the test.

  • Brief Visuospatial Memory Test-Revised (BVMT-R)Month 6

    The BVMT-R test involves a participant viewing a page of six figures for 10 seconds and then being asked to draw as many figures as they can remember in their correct places. This is repeated three times. Then, after a 25 minute interval, the examiner asks the participant to recall and draw the figures again. The BVMT-R is scored by summing how many items the participant correctly recalled for each trial. Higher scores indicate higher performance (greater cognitive capabilities) on the test.

  • Brief Visuospatial Memory Test-Revised (BVMT-R)Month 9

    The BVMT-R test involves a participant viewing a page of six figures for 10 seconds and then being asked to draw as many figures as they can remember in their correct places. This is repeated three times. Then, after a 25 minute interval, the examiner asks the participant to recall and draw the figures again. The BVMT-R is scored by summing how many items the participant correctly recalled for each trial. Higher scores indicate higher performance (greater cognitive capabilities) on the test.

  • Brief Visuospatial Memory Test-Revised (BVMT-R)Month 12

    The BVMT-R test involves a participant viewing a page of six figures for 10 seconds and then being asked to draw as many figures as they can remember in their correct places. This is repeated three times. Then, after a 25 minute interval, the examiner asks the participant to recall and draw the figures again. The BVMT-R is scored by summing how many items the participant correctly recalled for each trial. Higher scores indicate higher performance (greater cognitive capabilities) on the test.

  • Trail Making Test (TMT)Day 1 (prior to WBRT treatment)

    The TMT consists of two parts: Part A and Part B. In Part A, participants are asked to connect 25 circles numbered 1-25 in ascending order. In Part B, participants are asked to connect 13 circles alternating between numbers and letters in ascending order. Participants are asked to complete these tasks as quickly as they can without lifting their pen from the paper. The TMT is measured by the time in seconds that it takes participant to complete the tasks. Higher times indicate greater cognitive impairment.

  • Trail Making Test (TMT)Month 3

    The TMT consists of two parts: Part A and Part B. In Part A, participants are asked to connect 25 circles numbered 1-25 in ascending order. In Part B, participants are asked to connect 13 circles alternating between numbers and letters in ascending order. Participants are asked to complete these tasks as quickly as they can without lifting their pen from the paper. The TMT is measured by the time in seconds that it takes participant to complete the tasks. Higher times indicate greater cognitive impairment.

  • Trail Making Test (TMT)Month 6

    The TMT consists of two parts: Part A and Part B. In Part A, participants are asked to connect 25 circles numbered 1-25 in ascending order. In Part B, participants are asked to connect 13 circles alternating between numbers and letters in ascending order. Participants are asked to complete these tasks as quickly as they can without lifting their pen from the paper. The TMT is measured by the time in seconds that it takes participant to complete the tasks. Higher times indicate greater cognitive impairment.

  • Trail Making Test (TMT)Month 9

    The TMT consists of two parts: Part A and Part B. In Part A, participants are asked to connect 25 circles numbered 1-25 in ascending order. In Part B, participants are asked to connect 13 circles alternating between numbers and letters in ascending order. Participants are asked to complete these tasks as quickly as they can without lifting their pen from the paper. The TMT is measured by the time in seconds that it takes participant to complete the tasks. Higher times indicate greater cognitive impairment.

  • Trail Making Test (TMT)Month 12

    The TMT consists of two parts: Part A and Part B. In Part A, participants are asked to connect 25 circles numbered 1-25 in ascending order. In Part B, participants are asked to connect 13 circles alternating between numbers and letters in ascending order. Participants are asked to complete these tasks as quickly as they can without lifting their pen from the paper. The TMT is measured by the time in seconds that it takes participant to complete the tasks. Higher times indicate greater cognitive impairment.