Whole Brain Radiotherapy for Brain Cancer

Overseen By Haley Perlow, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Case Comprehensive Cancer Center

Disqualifiers: Multiple sclerosis, Alzheimer's, dementia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two methods of whole brain radiotherapy (HA-WBRT and MA-WBRT) for treating cancer that has spread to the brain. One method avoids the hippocampus, crucial for memory, while the other avoids additional brain structures that may aid thinking and memory. Researchers aim to determine which method better protects cognitive function. Individuals with at least 10 brain tumors who can receive whole brain radiotherapy might be suitable for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant findings.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that treatments like Memory Avoidance Whole Brain Radiation Therapy (MA-WBRT) and Hippocampal Avoidance Whole Brain Radiation Therapy (HA-WBRT) protect brain health while treating cancer that has spread to the brain.

Studies have found that HA-WBRT helps safeguard memory and overall brain function. Specifically, patients reported fewer issues with memory and thinking skills. One study showed that HA-WBRT reduced the risk of memory and thinking problems compared to other methods.

While fewer specific studies exist for MA-WBRT, similar treatments have been noted to help maintain brain functions like memory and thinking.

Both treatments aim to avoid harming parts of the brain important for memory and thinking while still targeting cancer cells. So far, they appear well-tolerated, focusing on reducing side effects related to brain function. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the new approaches to whole brain radiotherapy for brain cancer, specifically MA-WBRT and HA-WBRT, because they aim to minimize cognitive side effects. Unlike traditional whole brain radiation therapy, which often affects memory and cognitive function, MA-WBRT focuses on avoiding damage to memory-critical areas of the brain. Similarly, HA-WBRT targets the hippocampus, a region vital for memory, to reduce the risk of cognitive decline. These innovative techniques could mean better quality of life for patients by preserving memory and mental function while effectively treating cancer.

What evidence suggests that this trial's treatments could be effective for brain cancer?

This trial will compare two treatments: Memory Avoidance Whole Brain Radiation Therapy (MA-WBRT) and Hippocampal Avoidance Whole Brain Radiation Therapy (HA-WBRT). Research has shown that whole brain radiotherapy (WBRT) can treat cancer that has spread to the brain, but it often impacts memory and thinking skills. Participants receiving MA-WBRT, one of the treatments in this trial, demonstrated a lower rate of cognitive decline—about 17% at three months—compared to traditional WBRT, and generally have better memory scores over time. Meanwhile, HA-WBRT, another treatment option in this trial, aims to protect the hippocampus, a part of the brain crucial for memory. Early findings suggest both treatments strive to preserve thinking skills while treating brain cancer. Overall, these treatments aim to reduce memory problems while targeting cancer cells. ^{1 4 6 7 8}

Who Is on the Research Team?

Haley Perlow, MD

Principal Investigator

Case Comprehensive Cancer Center, University Hospitals

Are You a Good Fit for This Trial?

This trial is for individuals with cancer that has spread to the brain (brain metastases). Participants should be suitable for radiotherapy and willing to take medication aimed at preserving cognitive function. Specific eligibility criteria are not provided, but typically include factors like overall health status, age range, and absence of certain medical conditions.

Inclusion Criteria

Estimated life expectancy of at least 3 months

I am older than 18 years.

I am mostly independent and can care for myself.

Exclusion Criteria

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Memory Avoidance Whole Brain Radiotherapy (MA-WBRT) or Hippocampal Avoidance Whole Brain Radiotherapy (HA-WBRT) with memantine

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including cognitive assessments

12 months

What Are the Treatments Tested in This Trial?

Interventions

• HA-WBRT
• MA-WBRT

Trial Overview The Athena 2 Trial is comparing two types of whole brain radiotherapy: one avoids the hippocampus (HA-WBRT), while the other avoids additional areas linked to memory (MA-WBRT). Both methods are combined with a drug called Memantine. The goal is to see which better preserves cognitive functions in patients.

How Is the Trial Designed?

Group I: Memory Avoidance Whole Brain Radiation Therapy (MA-WBRT) Experimental Treatment 2 Interventions

Group II: Hippocampal Avoidance Whole Brain Radiation Therapy (HA-WBRT) Active Control 2 Interventions

Who Is Running the Clinical Trial?

Case Comprehensive Cancer Center

Lead Sponsor

Trials

472

Recruited

33,400+

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.2039

Initial report of memory avoidance whole brain ... Conclusions: The cognitive decline rate of approximately 17% at three months for patients receiving MA-WBRT compares favorably to a 3-month ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12123685/

Neurocognitive outcome of HS-WBRT vs WBRT in patients ... HS-WBRT demonstrates a clear advantage over WBRT in preserving neurocognitive function in patients with brain metastases, as reflected in HVLT and MoCA scores.

3. sciencedirect.com sciencedirect.com/science/article/pii/S2452109423001653

Dosimetric Results From a Phase 2 Trial of Memory ... We report our preliminary experience using a “memory-avoidance” WBRT (MA-WBRT) approach that spares these substructures for patients with >15 brain metastases.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03247127

Memory Preservation of Hippocampal Avoidance Whole ... The study aimed to investigate the memory preservation and neurocognitive function protection of hippocampal avoidance whole brain radiotherapy (HA-WBRT) among ...

5. academic.oup.com academic.oup.com/neuro-oncology/article/27/Supplement_3/iii110/8272362

P11.29.B WHOLE-BRAIN RADIATION THERAPY WITH DOSE ... Both arms experienced a decline in VLMT scores at three months. At the nine-month mark, cognitive scores improved, with Arm A trending more ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301623004388

Sustained Preservation of Cognition and Prevention ... With median follow-up exceeding 1 year, HA during WBRT + memantine for brain metastases leads to sustained preservation of cognitive function and continued ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.19.03359

Benefit of Treatment With Hippocampal Avoidance Whole ... This hippocampal avoidant WBRT (HA-WBRT) was tested in a phase II trial, with results supporting preservation of memory and quality of life (QOL) compared with ...

8. nrgoncology.org nrgoncology.org/Home/News/Post/nrg-oncology-trial-shows-hippocampal-avoidance-during-whole-brain-radiotherapy-for-brain-metastases-reduces-risks-of-cognitive-toxicity-and-neurologic-symptoms/

NRG Oncology Trial Shows Hippocampal Avoidance ... With a median follow up of 7.9 months, the risk of cognitive function failure was lower following hippocampal avoidance whole-brain radiotherapy ...