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

Launched by UNIVERSITY OF VERMONT MEDICAL CENTER · May 7, 2025

Keywords

ClinConnect Summary

This clinical trial is looking at whether some patients with brain metastases, particularly those with non-small cell lung cancer (NSCLC), can safely avoid radiation therapy if their brain lesions respond well to other treatments like chemotherapy, targeted therapy, or immunotherapy. The study will include 45 participants, with most having NSCLC and others with different types of solid tumors. To qualify, participants must have at least one brain metastasis that isn’t planned for surgery or radiation and must be starting a treatment that can affect the brain.

During the trial, patients will have a brain MRI about 4 to 8 weeks after starting their treatment. If their brain lesions are stable or getting smaller, they can continue to be monitored without radiation. If the lesions worsen, standard radiation treatment may be given if the doctor thinks it’s necessary. The main goal is to see how long patients can go without needing radiation while still receiving effective treatment. This study could help in understanding which patients might be able to avoid radiation in the future, potentially improving their quality of life.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Pathologically (histologically or cytologically) proven diagnosis of a solid tumor malignancies within 5 years prior to registration. If the original histologic proof of malignancy is greater than 5 years, then more recent pathologic confirmation (e.g., from a systemic site or brain metastasis) or unequivocal imaging confirmation of extracranial metastatic disease (e.g. CT of the chest/abdomen/pelvis, PET/CT, etc.) is required. These scans are considered standard-of-care (SOC) and will not be ordered for research purposes.
• Initiation or planning for initiation of systemic therapy to include one or more of the following categories expected to cause an intracranial response:
• • 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.
• Exclusion Criteria:
• • No use of the planned new systemic therapy meeting 2.1.2 criteria to address brain metastases within the last 6 months.
• • Prior radiotherapy to the active brain metastases (partial or whole brain irradiation, or prophylactic cranial irradiation \[PCI\])
• • Patients pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants. Negative urine pregnancy test (in persons of childbearing potential) within 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal.
• • Serious medical comorbidities that in the opinion of the investigator would prevent participation in this study.
• • Known leptomeningeal disease (LMD)
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