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

What this study is about

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.

Who can join (things the study team will check)

✅ You may be able to join if…

• Brain penetrant targeted therapies (e.g. tyrosine kinase inhibitors, multikinase inhibitors, EGFR inhibitor, ALK inhibitor, BRAF/MEK inhibitor)
• Checkpoint inhibitor immunotherapy (e.g. PDL-1 inhibitors, PD1 inhibitors, CTLA-4 inhibitors)
• HER2 antibody-drug conjugate (e.g. TDM1, TDX-D)
• Anti-Hormone therapies for Breast Cancer
• Cytotoxic chemotherapy alone may be started initially, but with plan for immunotherapy or eligible targeted therapy noted above before the re-evaluation MRI head At least 1 brain metastasis that not planned for radiation therapy or surgery. All brain metastases not planned for resection much be ≤3 cm, with no minimum size required. Systemic therapy has started within 4 weeks of MRI brain showing new or progressive disease or plan to start systemic therapy within 4 weeks of MRI brain showing new or progressive disease. Ability to obtain MRI head scans with contrast. All MRI head scans must have slice thickness ≤1.5 mm. Age ≥ 18 years KPS >60 Ability to understand and the willingness to sign a written informed consent.

Where this trial is running

• University of Vermont Medical Center, Burlington, Vermont, United States

Who to contact

Christopher Anker, MD · 1 802 656 2021 · chris.anker@uvmhealth.org

It's completely normal to call and ask questions before deciding anything. Mention the study ID: NCT06974370.