Optimizing Neurocognition With Whole Brain Radiation Therapy (WBRT) Using Upfront Pulsed Reduced Dose-Rate (PRDR) Technique

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to no maximum
• SexAll
• Healthy volunteersNo

You may be able to join if

• Age ≥18 years at diagnosis of brain metastases.
• Eastern Cooperative Oncology Group (ECOG) Performance Score of <2.
• Participants must have a biopsy-proven solid malignancy (histologic proof or unequivocal cytologic proof solid tumor malignancy from either the primary or any metastatic site) with intracranial lesions radiographically consistent with or pathologically proven to be brain metastases.
• Patients who have undergone prior systemic therapy are eligible.
• Life expectancy from extracranial disease greater than six months.
• Patients with measurable brain metastasis.
• Patients may have had prior therapy for brain metastasis, including stereotactic radiosurgery (SRS)and surgical resection. Patients must have completed prior therapy by at least 7 days prior to study enrollment for SRS and at least 14 days for surgical resection
• If an open biopsy is performed, the patient must be at least one-week post-biopsy. This requirement is not necessary for stereotactic biopsies.
• Creatinine clearance is ≥ 30 mL/min.
• Start of PRDR WBRT within two weeks following registration.
• Ability to complete the Neurocognitive Function (NCF) test battery (including people whose primary language is English).
• Patients with previous or other malignancies whose disease is controlled and not impacting ECOG performance or life expectancy.
• Willing and able to give consent and to comply with treatment and follow-up schedule.

You cannot join if

• Metastases from hematological malignancy, or central nervous system malignancy.
• Patients whose malignancy is being treated with curative intent.
• Leptomeningeal metastases.
• Contraindication to MRI imaging with contrast.
• Contraindication to memantine including concurrent use of N-methyl-D-aspartate (NMDA) antagonists.
• Stage IV-V chronic kidney disease or end-stage renal disease.
• Participants with a maximum tumor diameter exceeding 5 cm (if not resected).
• Prior cranial whole brain radiation therapy.
• Past medical history of dementia which is thought to be unrelated to the brain metastases.
• Women of childbearing potential who are known to be pregnant or are unwilling to use an acceptable method of contraception from the time of informed consent until completion of the course of radiotherapy.
• Patients must not have a serious medical or psychiatric illness that would, in the opinion of the treating physician, prevent informed consent or completion of protocol treatment, and/or follow-up visits.
• Non-native English speakers will be excluded since patients often lose their faculty with the language they acquired second before their native language is affected in the context of cognitive decline. This could adversely affect performance on verbal cognitive tasks.

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

Treatments listed in the registry

• Memantine -Twice Daily or Extended Release (Drug): Both extended release memantine and twice daily memantine dosing will be allowed. Twice daily dosing: The target dose for memantine is 20 mg (10 mg divided twice daily). Dose will be escalated by 5 mg each week to a target of 10 mg twice daily (i.e., 5 mg a day on week 1, then 5 mg twice daily (BID) on week 2, then 10 mg in AM plus 5 mg in PM on week 3, followed by 10 mg in AM plus 10 mg in PM by week 4). Extended Release Memantine: The target dose for extended release memantine is 28 mg. Dose will be escalated by 7 mg per week to a target of 28 mg daily (i.e., 7 mg a day on week 1, then 14 mg a day on week 2, then 21 mg a day on week 3, followed by 28 mg a day by week 4).
• WBRT utilizing the PRDR technique (Radiation): The total dose of 3000 cGy (30 Gy) will be divided 10 fractions of 300 cGy (3 Gy); each fraction will be delivered as a series of 20 cGy (0.2Gy) pulses separated by 3 min time intervals. 20 cGy / 3 min = 6.67 cGy/min (or 0.0667 Gy/min). Total time is determined by the fractionated series and time intervals, meaning 300cGy/20cGy = 15 division x 3 minutes = 45 minutes. Including time to set up, approximate total time per treatment session will be 60 minutes.

Na · Single Group · masking: None

As the registry describes them. Requirements to join, such as a tissue sample, are in the eligibility list above even when on-study procedures are optional. Ask the study team which steps apply to you.

• biopsy: Part of the study plan
• radiation: Part of the study plan

Main goals

• Successful completion of PRDR WBRT treatment (5 days)

Planned enrollment: 53 (estimated).

• Froedtert Hospital & the Medical College of Wisconsin, Milwaukee, Wisconsin
• Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin

Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT05045950

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Jul 28, 2026. Public record; not medical advice.