A Phase 2 interventional study of Questionnaire Administration and Stereotactic Radiosurgery in Metastatic Malignant Neoplasm in the Brain and Metastatic Malignant Solid Neoplasm, sponsored by Mayo Clinic. Recruiting at 7 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-01.
Sponsored by Mayo Clinic · Phase 2, Interventional, and Treatment
This phase II trial compares the effect of single fraction stereotactic radiosurgery to fractionated stereotactic radiosurgery for the treatment of patients with cancer that has spread to the brain (metastatic brain disease). Stereotactic radiosurgery (SRS) is a form of radiation therapy that focuses high-power energy on a small area of the body. This trial is being done to determine if single (one) fraction stereotactic radiosurgery is better than fractionated stereotactic radiosurgery or vice versa in controlling tumor and side effects in patients with tumors that have spread to the brain.
PRIMARY OBJECTIVE:
I. To ascertain if the composite endpoint of cumulative treatment failure, defined by time to either local failure or symptomatic radiation brain necrosis of the largest brain metastasis (target lesion), is increased with fractionated stereotactic radiosurgery (FSRS) compared to single fraction stereotactic radiosurgery (SSRS).
SECONDARY OBJECTIVES:
I. To ascertain whether there is improved overall survival in patients who undergo FSRS compared to patients who receive SSRS.
II. To tabulate and descriptively compare the post-treatment adverse events associated with the interventions, including the potential impact of immunotherapy and targeted therapy.
III. To compare rates of radiation necrosis in patients who receive FSRS to patients who receive SSRS.
IV. To evaluate if there is any difference in central nervous system (CNS) failure patterns (e.g. local, distant brain failure) in patients who receive FSRS compared to patients who receive SSRS.
V. To ascertain whether FSRS prolongs time to neurologic death as compared to SRS.
VI. To determine whether there is improved patient reported outcomes (Functional Assessment of Cancer Therapy [FACT]-Brain Symptom Index [FBrSI]-24) including quality of life for patients who receive FSRS compared to patients who receive SSRS.
VII. To evaluate if there is any difference in CNS failure patterns (e.g. local, distant brain failure) and symptomatic radiation necrosis rates in patients who are treated with gamma knife compared to patients who are treated with a linear accelerator platform.
VIII. To determine whether differences in time to local failure, time to necrosis, or their composite endpoint cumulative treatment failure differs between treatment arms (or other patient or treatment factors) when analyzed on a "per lesion" basis rather than the per patient basis utilized for the primary endpoint.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients undergo single fraction SRS. Patients also undergo magnetic resonance imaging (MRI) at screening and during follow up.
ARM B: Patients undergo fractionated SRS, for 3-5 treatments, given over no more than 8 days. Patients also undergo MRI at screening and during follow up.
After completion of study treatment, patients are followed up at 3 months, every 3 months for 2 years, and then every 6 months for 3 years.
1,960 studies on the registry are indexed under Brain Neoplasms; 516 are open to participants now.
This study's planned enrollment of 90 is above the median of 40 across 1,458 interventional studies indexed under Brain Neoplasms.
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Presence of presumed brain metastases from an extra-cerebral tumor site (e.g. lung, breast, prostate, etc.)
Size of brain metastases
Past radiosurgery or resection is allowed as long as no definitive evidence of progression in these locations
Exclusion Criteria:
Any patient with definitive evidence of leptomeningeal metastasis (LMD)
Patients undergo single fraction SRS. Patients also undergo MRI at screening and during follow up.
Other: Questionnaire Administration · Radiation: Stereotactic Radiosurgery · Procedure: Magnetic Resonance Imaging
Patients undergo fractionated SRS, for 3-5 treatments, given over no more than 8 days.. Patients also undergo MRI at screening and during follow up.
Other: Questionnaire Administration · Radiation: Stereotactic Radiosurgery · Procedure: Magnetic Resonance Imaging
Ancillary studies
Undergo single fraction SRS
Also known as: Stereotactic External Beam Irradiation, stereotactic external-beam radiation therapy, Stereotactic Radiation Therapy, Stereotactic Radiotherapy, stereotaxic radiation therapy, stereotaxic radiosurgery, SRS
Undergo fractionated SRS
Also known as: Stereotactic External Beam Irradiation, stereotactic external-beam radiation therapy, Stereotactic Radiation Therapy, Stereotactic Radiotherapy, stereotaxic radiation therapy, stereotaxic radiosurgery, SRS
Undergo MRI
Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MRI, MR Imaging, MRI Scan, MRIs, NMR Imaging, NMRI, nuclear magnetic resonance imaging, sMRI, Structural MRI
Time to local failure or symptomatic radiation brain necrosis of large brain metastasis
Will determine if the composite endpoint of time to local failure or symptomatic radiation brain necrosis of a large brain metastasis \[cumulative treatment failure (CTF)\] is increased with fractionated stereotactic radiosurgery (FSRS) compared to single fraction stereotactic radiosurgery (SSRS).
Time frame: Up to 5 years
Overall survival (OS)
OS will be estimated using the Kaplan-Meier method, where the log-rank test will be used to compare the 2 treatment arms. Medians and 95% confidence intervals will be reported.
Time frame: From study entry to death from any cause, assessed up to 5 years
Incidence of adverse events
The maximum grade for each type of adverse event will be summarized using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The frequency and percentage of grade 3+ adverse events will be compared between the 2 treatment arms. Comparisons between arms will be made by using either the Chi-square or Fisher's Exact test.
Time frame: Up to 2 years post radiation therapy
Rates of radiation necrosis
Will compare rates of radiation necrosis in patients who receive FSRS to patients who receive SSRS. Comparisons between arms will be made by using either the Chi-square or Fisher's Exact test.
Time frame: Up to 5 years
Central nervous system (CNS) failure patterns (Fractionation)
Will evaluate if there is any difference in CNS failure patterns (e.g. local, distant brain failure) in patients who receive FSRS compared to patients who receive SSRS. Comparisons between arms will be made by using either the Chi-square or Fisher's Exact test.
Time frame: Up to 5 years
Time to neurologic death
Will ascertain whether FSRS prolongs time to neurologic death as compared to SSRS. This will be estimated using the Kaplan-Meier method, where the log-rank test will be used to compare the 2 treatment arms. Medians and 95% confidence intervals will be reported.
Time frame: Up to 5 years
Quality of life (QOL)
Will determine whether there are improved patient reported outcomes (Functional Assessment of Cancer Therapy \[FACT\]-Brain Symptom Index \[FBrSI\]-24) including quality of life for patients who receive FSRS compared to patients who receive SSRS. Changes over time in QOL from baseline will be compared between arms using the 2-sample t-test (or Wilcoxon Rank-Sum test for non-normal data). Box-plots will be used to show differences between arms graphically.
Time frame: Up to 5 years
CNS failure patterns (Gamma Knife)
Will evaluate if there is any difference in CNS failure patterns (e.g. local, distant brain failure) and symptomatic radiation necrosis rates in patients who are treated with Gamma Knife compared to patients who are treated with a linear accelerator platform. Comparisons between arms will be made by using either the Chi-square or Fisher's Exact test.
Time frame: Up to 5 years
Per lesion analysis between treatment arms: time to local failure
Will determine whether differences in time to local failure differs between treatment arms (or other patient or treatment factors) when analyzed on a "per lesion" basis rather than the per patient basis utilized for the primary endpoint. Time-to-event models (Cox and Kaplan- Meier) with sandwich estimators for covariance will be utilized to in treatment comparisons, with model comparisons completed through log-likelihood and Akaike Information Criterion.
Time frame: Up to 5 years
Per lesion analysis between treatment arms: time to necrosis
Will determine whether differences in time to necrosis differs between treatment arms (or other patient or treatment factors) when analyzed on a "per lesion" basis rather than the per patient basis utilized for the primary endpoint. Time-to-event models (Cox and Kaplan- Meier) with sandwich estimators for covariance will be utilized to in treatment comparisons, with model comparisons completed through log-likelihood and Akaike Information Criterion.
Time frame: Up to 5 years
Per lesion analysis between treatment arms: endpoint CTF
Will determine whether differences in the composite endpoint CTF differs between treatment arms (or other patient or treatment factors) when analyzed on a "per lesion" basis rather than the per patient basis utilized for the primary endpoint. Time-to-event models (Cox and Kaplan- Meier) with sandwich estimators for covariance will be utilized to in treatment comparisons, with model comparisons completed through log-likelihood and Akaike Information Criterion.
Time frame: Up to 5 years
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