A Phase 3 interventional study of Single Fraction Stereotactic Radiosurgery and Fractionated Stereotactic Radiosurgery in Metastatic Malignant Neoplasm in the Brain, sponsored by Alliance for Clinical Trials in Oncology. Active, not recruiting at 232 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-17.
Sponsored by Alliance for Clinical Trials in Oncology · Phase 3, Interventional, and Treatment
This phase III trial studies how well single fraction stereotactic radiosurgery works compared with fractionated stereotactic radiosurgery in treating patients with cancer that has spread to the brain from other parts of the body (brain metastases) and has been removed by surgery (resected). Single fraction stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may cause less damage to normal tissue. Fractionated stereotactic radiosurgery delivers multiple, smaller doses of radiation therapy over time. This study may help doctors find out if fractionated stereotactic radiosurgery is better or worse than the usual approach with single fraction stereotactic radiosurgery.
PRIMARY OBJECTIVES:
I. To ascertain if time to surgical bed failure is increased with fractionated stereotactic radiosurgery (FSRS) compared to single-fraction stereotactic radiosurgery (SSRS) in patients with resected brain metastasis.
SECONDARY OBJECTIVES:
I. To ascertain if there is better emotional well-being at 9 months as assessed by the Functional Assessment of Cancer Therapy-Brain (FACT-BR) in patients with resected brain metastasis undergoing FSRS compared to SSRS (Primary quality of life [QOL] objective).
II. To ascertain whether there is improved overall survival in patients with resected brain metastases who undergo FSRS compared to patients who receive SSRS.
III. To ascertain in patients with resected brain metastases whether there is improved overall QOL as assessed by the FACT-BR and Linear Analog Self-Assessment (LASA) in patients who receive FSRS compared to patients who receive SSRS (Secondary QOL objective).
IV. To compare the functional independence in patients who receive FSRS to patients who receive SSRS.
V. To tabulate and descriptively compare the post-treatment adverse events associated with the interventions, including the potential impact of immunotherapy and targeted therapy.
VI. To compare rates of radiation necrosis at 12 months in patients who receive FSRS to patients who receive SSRS.
VII. To evaluate if there is any difference in central nervous system (CNS) failure patterns (local, distant brain failure, local leptomeningeal disease, widespread leptomeningeal disease) in patients who receive FSRS compared to patients who receive SSRS after resection of brain metastasis.
VIII. To ascertain in patients with resected brain metastases whether there is increased time to whole-brain radiotherapy (WBRT) in patients who receive FSRS compared to patients who receive SSRS.
IX. To determine in long-term survivors (patients who are alive more than 12 months from time of randomization) whether there is better emotional well-being and overall QOL as assessed by the FACT-BR and LASA in patients who receive FSRS to the surgical bed compared to patients who receive SSRS (Secondary QOL objective).
X. To assess for differences in CNS failure patterns (surgical, local, distant brain failure, leptomeningeal disease) as well as radiation necrosis rates as assessed by central review in patients who receive FSRS compared to patients who receive SSRS after resection of a brain metastasis.
XI. To ascertain in patients with resected brain metastases whether there is improved QOL as assessed by all other total and individual FACT-BR and LASA items and subscale values in patients who receive FSRS compared to patients who receive SSRS (Exploratory QOL objective).
XII. To determine in patients with resected brain metastases whether there is less cognitive progression in patients who receive FSRS to the surgical bed compared to patients who receive SSRS (Exploratory cognitive objective).
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients undergo SSRS over 1 session.
ARM II: Patients undergo FSRS over 3 or 5 daily sessions.
After completion of study, patients are followed up at 30 days, at 3, 6, 9, 12, 16, and 24 months, then every 6 months until 5 years from randomization.
1,960 studies on the registry are indexed under Brain Neoplasms; 516 are open to participants now.
This study's enrollment of 242 is above the median of 40 across 1,458 interventional studies indexed under Brain Neoplasms.
Browse Brain Neoplasms studies →Alliance for Clinical Trials in Oncology is the lead sponsor of 499 studies on the registry; 27 are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 6 (100%) have results posted.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria:
PRE-REGISTRATION:
Three or fewer (i.e. 0 to 3) unresected brain metastases (as defined on the post operative magnetic resonance imaging [MRI]) at the time of screening.
o Note: Dural based metastases (e.g. commonly seen in breast cancer) are eligible.
Unresected lesions must measure \< 4.0 cm in maximal extent on the contrasted post-operative treatment MRI brain scan. The unresected lesions will be treated with SRS as outlined in the treatment section of the concept.
o Note: The metastases size restriction does not apply to the resected brain metastasis.
One brain metastasis must be completely (gross total resection) resected =\< 30 days prior to pre-registration.
o NOTE: May not have had resection of more than one brain metastasis.
For women of childbearing potential only, a negative urine or serum pregnancy test done =\< 7 days prior to pre-registration is required.
Past radiosurgery to other lesions is allowed.
o NOTE: The surgically resected lesion cannot be the same location treated in the past with radiosurgery (i.e. repeat radiosurgery to the same location/lesion is not allowed on this protocol).
No evidence of leptomeningeal metastasis (LMD).
o NOTE: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive cerebrospinal fluid (CSF) cytology and/or equivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology, unless a parenchymal lesion can adequately explain the neurologic symptoms and/or signs. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In that patient, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion.
REGISTRATION:
Patients undergo SSRS over 1 session.
Radiation: Single Fraction Stereotactic Radiosurgery · Procedure: Quality-of-Life Assessment · Other: Questionnaire Administration
Patients undergo FSRS over 3 or 5 daily sessions.
Radiation: Fractionated Stereotactic Radiosurgery · Procedure: Quality-of-Life Assessment · Other: Questionnaire Administration
Undergo SSRS
Also known as: Stereotactic Radiosurgery
Undergo FSRS
Also known as: Stereotactic Radiosurgery
Ancillary studies
Ancillary studies
Surgical bed recurrence-free survival (SB-RFS)
Surgical bed control is defined as the absence of new nodular contrast enhancement in the surgical bed. In other words, a surgical bed recurrence-free survival (SB-RFS) event is defined as radiographic evidence of a new contrast-enhancing lesion (specifically any new progressive enhancing nodularity) at the site of the surgical resection. Will use a stratified log-rank test that compares and will report the median SB-RFS times between the single fraction stereotactic radiosurgery (SSRS) and fractionated stereotactic radiosurgery (FSRS) arms while adjusting for the stratification factors.
Time frame: From the time of randomization up to 2 years post radiation
Change in Functional Assessment of Cancer Therapy-Brain (FACT-BR) Emotional sub-scale score
The average change from baseline to 9 months in the Functional Assessment of Cancer Therapy-Brain (FACT-BR) Emotional sub-scale will be compared between randomization arms.
Time frame: At 9 months
Functional Assessment of Cancer Therapy-Brain (FACT-BR) total score
The average change from baseline to 9 months in the Functional Assessment of Cancer Therapy-Brain (FACT-BR) total score will be compared between randomization arms.
Time frame: At 9 months
Linear Analog Self-Assessment (LASA) overall quality of life
The average change from baseline to 9 months in the Linear Analog Self-Assessment (LASA) overall total score will be compared between randomization arms.
Time frame: At 9 months
Functional Assessment of Cancer Therapy-Brain (FACT-BR) Emotional sub-scale score for long-term survivors
Long-term survivors defined as patients who are alive more than 12 months from time of randomization. The average change from baseline to 12 months in the Functional Assessment of Cancer Therapy-Brain (FACT-BR) Emotional sub-scale for the long-term survivors will be compared between randomization arms.
Time frame: At 12 months
Functional Assessment of Cancer Therapy-Brain (FACT-BR) total score for long-term survivors
Long-term survivors defined as patients who are alive more than 12 months from time of randomization. The average change from baseline to 12 months in the Functional Assessment of Cancer Therapy-Brain (FACT-BR) total score for the long-term survivors will be compared between randomization arms.
Time frame: At 12 months
Linear Analog Self-Assessment (LASA) overall quality of life for long-term survivors
Long-term survivors defined as patients who are alive more than 12 months from time of randomization. The average change from baseline to 9 months in the Linear Analog Self-Assessment (LASA) overall total score for the long-term survivors will be compared between randomization arms.
Time frame: At 12 months
Karnofsky Performance Status (KPS)
The duration of Karnofsky Performance Status (KPS) functional independence will be the time to when the KPS scores per patient decrease below their baseline level and will be compared between treatment arms by the logrank test. Median durations of KPS functional independence will be reported and compared between randomization arms.
Time frame: Up to 24 months
Barthel Activities of Daily Living (ADL) Index
The duration of Barthel Activities of Daily Living (ADL) functional independence will be the time to when the ADL scores per patient decrease below their baseline level and will be compared between treatment arms by the logrank test. Median durations of ADL functional independence will be reported and compared between randomization arms.
Time frame: Up to 24 months
Karnofsky Performance Status (KPS) for long-term survivors
Long-term survivors defined as patients who are alive more than 12 months from time of randomization. The duration of Karnofsky Performance Status (KPS) functional independence will be the time to when the KPS scores per patient decrease below their baseline level and will be compared between treatment arms by the logrank test. Median durations of KPS functional independence for long-term survivors will be reported and compared between randomization arms.
Time frame: Up to 24 months
Barthel Activities of Daily Living (ADL) Index for long-term survivors
Long-term survivors defined as patients who are alive more than 12 months from time of randomization. The duration of Barthel Activities of Daily Living (ADL) functional independence will be the time to when the ADL scores per patient decrease below their baseline level and will be compared between treatment arms by the logrank test. Median durations of ADL functional independence for long-term survivors will be reported and compared between randomization arms.
Time frame: Up to 24 months
Overall survival
Overall survival time will be compared between the treatment arms using a stratified log-rank test. If the proportional hazards assumption is violated, a restricted means analysis will be used to compare overall survival between the two treatment arms. Median survival times per treatment arms will be reported.
Time frame: Up to 5 years
Incidence of adverse events
The Common Terminology Criteria for Adverse Events version 5.0 will be used. The proportion of patients experiencing any adverse event will be compared between the two treatment arms using a chi-square (or Fisher's exact test, if more appropriate).
Time frame: Up to 24 months
Proportion of patients with radiation necrosis
The proportion of patients with radiation necrosis within 24 months from of starting treatment will be compared between the treatment arms with a chi-square test (or Fisher's exact test if more appropriate).
Time frame: At 24 months
Time until whole-brain radiotherapy (WBRT) due to any reason (e.g. surgical bed recurrence, recurrence/progression at another central nervous system [CNS] site)
Time until whole-brain radiotherapy (WBRT) will be compared between the treatment arms using a stratified log-rank test. Median time until WBRT per treatment arms will be reported.
Time frame: Up to 24 months
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Plan to share: Yes
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Alliance for Clinical Trials in Oncology