Using a new radiation technique to treat brain metastases

Optimizing Neurocognition With Whole Brain Radiation Therapy (WBRT) Using Upfront Pulsed Reduced Dose-Rate (PRDR) Technique (ONCO-RT) - A Phase II Trial of Upfront Pulsed Reduced Dose Rate Whole-Brain Radiation Therapy for Brain Metastases

This study is testing a new way of giving radiation to treat brain tumors in adults to see if it helps them tolerate the treatment better and protects their thinking skills.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 53 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Medical College of Wisconsin (Academic / other)
• Drugs / interventions: radiation
• Locations: 2 sites (Milwaukee, Wisconsin and 1 other locations)
• Trial ID: NCT05045950 on ClinicalTrials.gov

What this trial studies

This phase II, single-arm, multi-center study evaluates the feasibility and tolerance of whole-brain radiation therapy (WBRT) using an upfront pulsed reduced dose-rate (PRDR) technique for patients with solid tumor brain metastases. Participants will receive a total dose of 30 Gy in 10 fractions of PRDR WBRT within 14 days of registration, along with memantine to assess its impact on neurocognitive decline compared to historical controls. The study aims to enroll 53 adult patients and includes an interim analysis after the first 27 patients to determine feasibility and preliminary outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with biopsy-proven solid malignancies and measurable brain metastases.

Not a fit: Patients with an ECOG performance score of 2 or higher or those with a life expectancy of less than six months from extracranial disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve neurocognitive outcomes for patients undergoing treatment for brain metastases.

How similar studies have performed: While the use of PRDR in WBRT is a novel approach, similar studies have shown promise in improving outcomes in radiation therapy for brain metastases.

Eligibility criteria

Inclusion Criteria:

1. Age ≥18 years at diagnosis of brain metastases.
2. Eastern Cooperative Oncology Group (ECOG) Performance Score of \<2.
3. 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.
4. Patients who have undergone prior systemic therapy are eligible.
5. Life expectancy from extracranial disease greater than six months.
6. Patients with measurable brain metastasis.
7. 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
8. If an open biopsy is performed, the patient must be at least one-week post-biopsy. This requirement is not necessary for stereotactic biopsies.
9. Creatinine clearance is ≥ 30 mL/min.
10. Start of PRDR WBRT within two weeks following registration.
11. Ability to complete the Neurocognitive Function (NCF) test battery (including people whose primary language is English).
12. Patients with previous or other malignancies whose disease is controlled and not impacting ECOG performance or life expectancy.
13. Willing and able to give consent and to comply with treatment and follow-up schedule.

Exclusion Criteria:

1. Metastases from hematological malignancy, or central nervous system malignancy.
2. Patients whose malignancy is being treated with curative intent.
3. Leptomeningeal metastases.
4. Contraindication to MRI imaging with contrast.
5. Contraindication to memantine including concurrent use of N-methyl-D-aspartate (NMDA) antagonists.
6. Stage IV-V chronic kidney disease or end-stage renal disease.
7. Participants with a maximum tumor diameter exceeding 5 cm (if not resected).
8. Prior cranial whole brain radiation therapy.
9. Past medical history of dementia which is thought to be unrelated to the brain metastases.
10. 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.
11. 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.
12. 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.

Where this trial is running

Milwaukee, Wisconsin and 1 other locations

• Froedtert Hospital & the Medical College of Wisconsin — Milwaukee, Wisconsin, United States (Recruiting)
• Clement J. Zablocki Veterans Affairs Medical Center — Milwaukee, Wisconsin, United States (Recruiting)

Study contacts

• Principal investigator: Michael Straza, MD — Medical College of Wisconsin
• Study coordinator: Medical College of Wisconsin Cancer Center Clinical Trials Office

Conditions Brain Metastases; whole-brain radiation therapy; upfront pulsed reduced dose-rate