NCT06974370

Avoiding Radiation Therapy Due to Intracranial Response to Chemotherapy, Targeted Therapy and/or Immuno-ONcology Therapy for Brain Metastases: Pilot Pragmatic Trial

Avoiding Radiation Therapy Due to Intracranial Response to Chemotherapy, Targeted Therapy and/or Immuno-ONcology Therapy for Brain Metastases: Pilot Pragmatic Trial (ACTION-Brain Metastases: Pilot Pragmatic Trial)

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 45 (estimated)
• Sponsor: University of Vermont Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This pilot pragmatic trial evaluates the feasibility of avoiding radiation therapy in patients with brain metastases who demonstrate an intracranial response to systemic therapy-including immunotherapy, targeted therapy, and/or chemotherapy. The study will prospectively enroll 45 patients, divided into two cohorts: 30 with non-small cell lung cancer (NSCLC) receiving immunotherapy, and 15 with brain metastases from other solid tumors. Eligible participants must have at least one brain metastasis not planned for radiation or surgery and must be initiating or planning to initiate a systemic therapy regimen expected to penetrate the blood-brain barrier and achieve intracranial activity. All patients will undergo a re-evaluation brain MRI 4-8 weeks after initiating systemic therapy. If lesions are stable or regressing, patients will continue surveillance without radiation. If progression is noted, standard-of-care radiation may be administered at the discretion of the treating physician. The primary objective is to assess 6-month radiation therapy-free survival (RTFS) in NSCLC patients based on PD-L1 expression status. Secondary endpoints include intracranial progression-free survival, overall survival, radiation necrosis rate, and quality of life. This study seeks to inform future trial design and identify patients who may safely avoid brain radiation.

Detailed description

This pilot pragmatic trial evaluates the feasibility of avoiding radiation therapy in patients with brain metastases who demonstrate an intracranial response to systemic therapy-including immunotherapy, targeted therapy, and/or chemotherapy. The study will prospectively enroll 45 patients, divided into two cohorts: 30 with non-small cell lung cancer (NSCLC) receiving immunotherapy, and 15 with brain metastases from other solid tumors. Eligible participants must have at least one brain metastasis not planned for radiation or surgery and must be initiating or planning to initiate a systemic therapy regimen expected to penetrate the blood-brain barrier and achieve intracranial activity. All patients will undergo a re-evaluation brain MRI 4-8 weeks after initiating systemic therapy. If lesions are stable or regressing, patients will continue surveillance without radiation. If progression is noted, standard-of-care radiation may be administered at the discretion of the treating physician. The primary objective is to assess 6-month radiation therapy-free survival (RTFS) in NSCLC patients based on PD-L1 expression status. Secondary endpoints include intracranial progression-free survival, overall survival, radiation necrosis rate, and quality of life. This study seeks to inform future trial design and identify patients who may safely avoid brain radiation. Detailed Description Brain metastases are the most common tumors of the central nervous system. Historically, treatment has included surgical resection followed by whole-brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) to prevent recurrence. While effective at achieving local control, radiation therapy-particularly WBRT-carries a significant risk of cognitive decline and radiation necrosis, especially in patients with longer life expectancies. Recent advances in systemic therapy-including immune checkpoint inhibitors, tyrosine kinase inhibitors, and other targeted agents-have demonstrated meaningful intracranial activity, especially in NSCLC, the most common source of brain metastases. Despite these advances, little prospective data exists on the safety and efficacy of deferring radiation therapy in patients responding to systemic treatment. This pilot study aims to assess the feasibility of delaying or omitting brain radiation therapy in patients whose brain metastases respond to systemic therapy. It is a prospective, single-institution study enrolling 45 participants across two cohorts: 30 NSCLC patients receiving immunotherapy and 15 patients with brain metastases from other cancer types. Eligible patients must be initiating systemic therapy with agents expected to cross the blood-brain barrier and have at least one brain metastasis not planned for surgical resection or radiation therapy. Patients will undergo a re-evaluation MRI 4-8 weeks after starting systemic therapy. If metastases are stable or regressing, radiation will be deferred and the patient will enter a structured surveillance protocol with MRIs every 3 months for up to 2 years. If progression is observed, patients may receive radiation therapy per standard of care. The primary objective is to determine the variability in 6-month RT-free survival (RTFS) in NSCLC patients with brain metastases based on PD-L1 expression. Secondary objectives include: Assessing 6-month RTFS in other histologies Measuring local and distant intracranial progression-free survival Evaluating intracranial objective response rate using iRANO criteria Determining the number of metastases avoiding radiation Measuring overall survival, disease-specific survival, and radiation necrosis rate Evaluating quality of life using FACT-Br and neurologic function via the NANO scale The study is exploratory and descriptive, with outcomes expected to inform the design of future cooperative group trials. It also complements ongoing trials like NRG-BN013 by evaluating outcomes in a population managed initially without radiation.

Conditions

• Brain Metastases, Adult
• Brain Metastases From Non-small Cell Lung Cancer (NSCLC)

Interventions

Type	Name	Description
RADIATION	Active Surveillance	Following systemic therapy, participants will undergo active surveillance with brain MRI every 3 months. Radiation therapy will only be initiated if disease progression is observed on imaging, at the discretion of the treating physician.

Timeline

• Start date: 2025-12-01
• Primary completion: 2030-12-01
• Completion: 2030-12-01
• First posted: 2025-05-15
• Last updated: 2025-05-15

Locations

1 site across 1 country: United States