Nervous System Diseases

All Conditions

Brain Diseases

Central Nervous System Diseases

Patients undergo FSRS over 3 or 5 daily sessions.

Single Fraction Stereotactic Radiosurgery

Fractionated Stereotactic Radiosurgery

Quality-of-Life Assessment

Questionnaire Administration

Paul D. Brown, MD

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 and has been removed by surgery. 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.

Single Fraction Stereotactic Radiosurgery Compared With Fractionated Stereotactic Radiosurgery in Treating Patients With Resected Metastatic Brain Disease

Phase III Trial of Post-Surgical Single Fraction Stereotactic Radiosurgery (SRS) Compared With Fractionated SRS for Resected Metastatic Brain Disease

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.

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.

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.

The average change from baseline to 9 months in the Linear Analog Self-Assessment (LASA) overall total score will be compared between randomization arms.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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 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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Single Fraction Stereotactic Radiosurgery Compared With Fractionated Stereotactic Radiosurgery in Treating Patients With Resected Metastatic Brain Disease	NCT04114981	Metastatic Mali...	Single Fraction... Fractionated St... Quality-of-Life... Questionnaire A...	18 Years -	Alliance for Clinical Trials in Oncology
Single Fraction Stereotactic Radiosurgery Compared With Fractionated Stereotactic Radiosurgery in Treating Patients With Resected Metastatic Brain Disease	NCT04114981	Metastatic Mali...	Single Fraction... Fractionated St... Quality-of-Life... Questionnaire A...	18 Years -	Alliance for Clinical Trials in Oncology
Single Fraction Stereotactic Radiosurgery Compared With Fractionated Stereotactic Radiosurgery in Treating Patients With Resected Metastatic Brain Disease	NCT04114981	Metastatic Mali...	Single Fraction... Fractionated St... Quality-of-Life... Questionnaire A...	18 Years -	Alliance for Clinical Trials in Oncology

Spots Global Cancer Trial Database for single fraction stereotactic radiosurgery