A Phase 2 interventional study of Active Surveillance in Brain Metastases, Adult and Brain Metastases From Non-small Cell Lung Cancer (NSCLC), sponsored by University of Vermont Medical Center. Recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-05-26.
Sponsored by University of Vermont Medical Center · Phase 2, Interventional, and Treatment
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.
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.
2,440 studies on the registry are indexed under Brain Neoplasms; 540 are open to participants now.
This study's planned enrollment of 45 is above the median of 40 across 1,831 interventional studies indexed under Brain Neoplasms.
Browse Brain Neoplasms studies →University of Vermont Medical Center is the lead sponsor of 43 studies on the registry; 19 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Pathologically (histologically or cytologically) proven diagnosis of a solid tumor 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 ) or unequivocal imaging confirmation of extracranial 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:
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
>60
Ability to understand and the willingness to sign a written .
Exclusion Criteria:
No use of the planned new systemic therapy meeting 2.1.2 criteria to address 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 ) 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 .
Serious medical comorbidities that in the opinion of the investigator would prevent participation in this study.
Known (LMD)
-
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Brain metastases
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
PD-1, PD-L1 and checkpoint inhibitors
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HER2
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Karnofsky performance status (KPS)
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Leptomeningeal disease
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants with brain metastases from solid tumors will receive standard-of-care systemic therapy expected to have intracranial activity, such as immunotherapy, targeted therapy, or anti-HER2 agents. A re-evaluation brain MRI will be performed 4-8 weeks after starting therapy. If lesions are stable or responding, patients will continue on systemic therapy with MRI surveillance every 3 months. Radiation therapy may be administered only if progression is observed. All participants are managed according to this pathway, regardless of primary tumor type.
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.
6-Month Radiation Therapy-Free Survival (RTFS) by PD-L1 Status in NSCLC Patients with Brain Metastases
To determine variability in 6-month RT-free survival (RTFS) in Non-Small Cell Lung Carcinoma (NSCLC) patients with brain metastases depending on PDL-1 status receiving systemic therapy including immunotherapy
Time frame: 6 months from baseline brain MRI
6-month RTFS
To determine 6-month RTFS in patients with brain metastases for histologies other than NSCLC receiving systemic therapy expected to have intracranial activity and NSCLC patients receiving systemic therapy other than immunotherapy expected to have intracranial activity
Time frame: 6 months from baseline brain MRI
Plan to share: No
No publications or documents are linked to this record.
Started Jun 2025 (actual). Primary completion is estimated for Dec 2030, 66 months after the start.
Of 208 non-industry phase 2 interventional studies under Brain Neoplasms, half reached primary completion within 67 months of starting (the median), counting those still running; a quarter within 43 and three quarters within 100. This study's planned 66 months is close to that.
Counting every sponsor, half of 252 studies reached it within 61 months; a quarter within 38 and three quarters within 98.
How these figures are worked out, and which studies are left out of them.
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