Brain MetastasesPhase 2NCT07248228
Memory Avoidance Whole Brain Radiotherapy vs Hippocampal Avoidance Whole Brain Radiotherapy (Athena 2 Trial)
A Phase 2 study testing MA-WBRT (Memory Avoidance Whole Brain Radiation Therapy (MA-WBRT)), HA-WBRT (Hippocampal Avoidance Whole Brain Radiation Therapy (HA-WBRT)) and Memantine in people with Brain Metastases, run by Case Comprehensive Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Metastases
- What is being tested?
- MA-WBRT (Memory Avoidance Whole Brain Radiation Therapy (MA-WBRT)), HA-WBRT (Hippocampal Avoidance Whole Brain Radiation Therapy (HA-WBRT)) and Memantine
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Jul 2026to Nov 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106
Haley Perlow, MD
Haley Perlow, MD
About this study
Official title: A Randomized Phase 2 Trial of Memory Avoidance Whole Brain Radiotherapy Versus Hippocampal Avoidance Whole Brain Radiotherapy (Athena 2 Trial)
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.
Read the 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
- Being tested
- MA-WBRT (Memory Avoidance Whole Brain Radiation Therapy (MA-WBRT)), HA-WBRT (Hippocampal Avoidance Whole Brain Radiation Therapy (HA-WBRT)), Memantine
- Keywords
- Whole brain radiotherapy, Memory-avoidance whole brain radiotherapy, Hippocampal-avoidance whole brain radiotherapy
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MA-WBRT (Memory Avoidance Whole Brain Radiation Therapy (MA-WBRT))Radiation
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.
HA-WBRT (Hippocampal Avoidance Whole Brain Radiation Therapy (HA-WBRT))Radiation
Participants will receive 10 daily fractions of WBRT per standard of care. Participants receiving HA-WBRT will receive WBRT that avoids the hippocampus.
MemantineDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| Memory Avoidance Whole Brain Radiation Therapy (MA-WBRT) | Experimental | Not described Receives: Radiation: MA-WBRT (Memory Avoidance Whole Brain Radiation Therapy (MA-WBRT)); Drug: Memantine |
| Hippocampal Avoidance Whole Brain Radiation Therapy (HA-WBRT) | Active comparator | Not described Receives: Radiation: HA-WBRT (Hippocampal Avoidance Whole Brain Radiation Therapy (HA-WBRT)); Drug: Memantine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to neurocognitive failure (NCF)
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.
Measured: Up to 12 months
Hopkins Verbal Learning Test-Revised (HVLT-R)
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.
Measured: Day 1 (prior to WBRT treatment)
Hopkins Verbal Learning Test-Revised (HVLT-R)
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.
Measured: Month 3
Hopkins Verbal Learning Test-Revised (HVLT-R)
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.
Measured: Month 6
Hopkins Verbal Learning Test-Revised (HVLT-R)
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.
Measured: Month 9
Hopkins Verbal Learning Test-Revised (HVLT-R)
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.
Measured: Month 12
Controlled Oral Word Association Test (COWAT)
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.
Measured: Day 1 (prior to WBRT treatment)
Controlled Oral Word Association Test (COWAT)
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.
Measured: Month 3
Controlled Oral Word Association Test (COWAT)
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.
Measured: Month 6
Controlled Oral Word Association Test (COWAT)
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.
Measured: Month 9
Controlled Oral Word Association Test (COWAT)
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.
Measured: Month 12
Brief Visuospatial Memory Test-Revised (BVMT-R)
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.
Measured: Day 1 (prior to WBRT treatment)
Brief Visuospatial Memory Test-Revised (BVMT-R)
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.
Measured: Month 3
Brief Visuospatial Memory Test-Revised (BVMT-R)
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.
Measured: Month 6
Brief Visuospatial Memory Test-Revised (BVMT-R)
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.
Measured: Month 9
Brief Visuospatial Memory Test-Revised (BVMT-R)
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.
Measured: Month 12
Trail Making Test (TMT)
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.
Measured: Day 1 (prior to WBRT treatment)
Trail Making Test (TMT)
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.
Measured: Month 3
Trail Making Test (TMT)
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.
Measured: Month 6
Trail Making Test (TMT)
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.
Measured: Month 9
Trail Making Test (TMT)
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.
Measured: Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2025
- Study start9 Jul 2026
- Primary completionMay 2027 (estimated)
- Study completionNov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Brain MetastasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Case Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Haley Perlow, MD, Principal investigator, Case Comprehensive Cancer Center, University Hospitals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07248228
- Sponsor's protocol ID
- CASE7325
- Status last verified
- Sep 2026
- First submitted
- 18 Nov 2025
- Last updated
- 22 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Palmer JD, Dawson EL, Sun Y, Yu J, Dibs K, Ritter AR, Boulter D, Nalin AP, Singh R, Beyer SJ, Zhu S, Blakaj DM, Grecula JC, Raval RR, Vazquez S, Whitman S, Presley CJ, Pillainayagam C, Giglio P, Thomas EM, Perlow HK. An initial report of memory avoidance whole brain radiotherapy to treat brain metastases. Neurooncol Adv. 2026 Aug 13;8(1):vdag211. doi: 10.1093/noajnl/vdag211. eCollection 2026 Jan-Dec.
PubMed 42677319
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase 2 Trial of Memory Avoidance Whole Brain Radiotherapy Versus Hippocampal Avoidance Whole Brain Radiotherapy (Athena 2 Trial)
- ClinicalTrials.gov ID
- NCT07248228
- Acronym / sponsor ID
- CASE7325
- Conditions
- Brain Metastases
- Keywords
- Whole brain radiotherapy, Memory-avoidance whole brain radiotherapy, Hippocampal-avoidance whole brain radiotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Case Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- 9 Jul 2026 (actual)
- Primary completion
- May 2027 (estimated)
- Study completion
- Nov 2028 (estimated)
- First posted
- 25 Nov 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Memory Avoidance Whole Brain Radiation Therapy (MA-WBRT) | Experimental | Radiation: MA-WBRT (Memory Avoidance Whole Brain Radiation Therapy (MA-WBRT)), Drug: Memantine |
| Hippocampal Avoidance Whole Brain Radiation Therapy (HA-WBRT) | Active comparator | Radiation: HA-WBRT (Hippocampal Avoidance Whole Brain Radiation Therapy (HA-WBRT)), Drug: Memantine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (5 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Memory Avoidance Whole Brain Radiation Therapy (MA-WBRT) |
| 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. | Radiation | Hippocampal Avoidance Whole Brain Radiation Therapy (HA-WBRT) |
| MemantineMemantine 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). | Drug | Hippocampal Avoidance Whole Brain Radiation Therapy (HA-WBRT), Memory Avoidance Whole Brain Radiation Therapy (MA-WBRT) |
Primary outcome
Time to neurocognitive failure (NCF)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2026.
- Derived from this study: PubMed 42677319Palmer JD, Dawson EL, Sun Y, Yu J, Dibs K, Ritter AR, Boulter D, Nalin AP, Singh R, Beyer SJ, Zhu S, Blakaj DM, Grecula JC, Raval RR, Vazquez S, Whitman S, Presley CJ, Pillainayagam C, Giglio P, Thomas EM, Perlow HK. An initial report of memory avoidance whole brain radiotherapy to treat brain metastases. Neurooncol Adv. 2026 Aug 13;8(1):vdag211. doi: 10.1093/noajnl/vdag211. eCollection 2026 Jan-Dec.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Haley Perlow, MD principal investigator
Case Comprehensive Cancer Center, University Hospitals
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MA-WBRT (Memory Avoidance Whole Brain Radiation Therapy (MA-WBRT)), HA-WBRT (Hippocampal Avoidance Whole Brain Radiation Therapy (HA-WBRT)) and Memantine in people with Brain Metastases, run by Case Comprehensive Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Haley Perlow, MD ((216) 286-3906, haley.perlow@uhhospitals.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to neurocognitive failure (NCF) (time frame: Up to 12 months). The study lists 21 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07248228, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2026.