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

Metastatic Malignant Neoplasm in the Brain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04114981
• Other study ID #: A071801
• Secondary ID: NCI-2019-02394U1
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 11, 2019
• Est. completion date: March 2028

Study information

• Verified date: August 2023
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 242
• Est. completion date: March 2028
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

PRE-REGISTRATION:

• Pathology from the resected brain metastasis must be consistent with a non-central nervous system primary site. Patients with or without active disease outside the nervous system are eligible (including patients with unknown primaries), as long as the pathology from the brain is consistent with a non-central nervous system primary site.

• 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.

• The resected brain metastasis must measure 2 cm or larger on the pre-operative MRI.

• Resection cavity must measure < 5.0 cm in maximal extent and the resection must be complete (gross total resection) on the post-operative MRI obtained =< 30 days prior to pre-registration.

• Karnofsky performance status of >= 60.

• For women of childbearing potential only, a negative urine or serum pregnancy test done =< 7 days prior to pre-registration is required.

• Men and women of childbearing potential must be willing to employ adequate contraception throughout the study and for men for up to 3 months after completing treatment.

• A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).

• Ability to complete an MRI of the head with contrast.

• The brain metastasis must be located > 5 mm of the optic chiasm; the brain metastasis must be located outside the brainstem (i.e. not inside the brainstem).

• Must not have any prior whole brain radiation therapy.

• 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).

• May not have primary germ cell tumor, small cell carcinoma, or lymphoma.

• 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.

• Must be fluent in English, Spanish, or French.

REGISTRATION:

• Completion of all baseline electronic patient-reported outcome (ePRO) quality of life measures (or booklet quality of life measures) and Montreal Cognitive Assessment (MoCA).

Related Conditions & MeSH terms

• Brain Diseases
• Metastatic Malignant Neoplasm in the Brain
• Neoplasms

Intervention

Radiation:
• Single Fraction Stereotactic Radiosurgery
Undergo SSRS
• Fractionated Stereotactic Radiosurgery
Undergo FSRS

Procedure:
• Quality-of-Life Assessment
Ancillary studies

Other:
• Questionnaire Administration
Ancillary studies

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	CHUM - Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec
Canada	Jewish General Hospital	Montreal	Quebec
Canada	The Research Institute of the McGill University Health Centre (MUHC)	Montreal	Quebec
Canada	CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)	Quebec City	Quebec
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	University Health Network-Princess Margaret Hospital	Toronto	Ontario
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Mary Greeley Medical Center	Ames	Iowa
United States	McFarland Clinic - Ames	Ames	Iowa
United States	Community Hospital of Anaconda	Anaconda	Montana
United States	Anchorage Radiation Therapy Center	Anchorage	Alaska
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Northwest Wisconsin Cancer Center	Ashland	Wisconsin
United States	Emory Saint Joseph's Hospital	Atlanta	Georgia
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	University of Colorado Hospital	Aurora	Colorado
United States	Saint Alphonsus Medical Center-Baker City	Baker City	Oregon
United States	Saint Louis Cancer and Breast Institute-Ballwin	Ballwin	Missouri
United States	MedStar Franklin Square Medical Center/Weinberg Cancer Institute	Baltimore	Maryland
United States	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana
United States	Woman's Hospital	Baton Rouge	Louisiana
United States	McLaren Cancer Institute-Bay City	Bay City	Michigan
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	Billings Clinic Cancer Center	Billings	Montana
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Boca Raton Regional Hospital	Boca Raton	Florida
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Parkland Health Center-Bonne Terre	Bonne Terre	Missouri
United States	McFarland Clinic - Boone	Boone	Iowa
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Cox Cancer Center Branson	Branson	Missouri
United States	Saint Joseph Mercy Brighton	Brighton	Michigan
United States	Ascension Southeast Wisconsin Hospital - Elmbrook Campus	Brookfield	Wisconsin
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho
United States	Cambridge Medical Center	Cambridge	Minnesota
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Joseph Mercy Canton	Canton	Michigan
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Memorial Hospital of Carbondale	Carbondale	Illinois
United States	SIH Cancer Institute	Carterville	Illinois
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	Saint Joseph Mercy Chelsea	Chelsea	Michigan
United States	Northwestern University	Chicago	Illinois
United States	University of Cincinnati Cancer Center-UC Medical Center	Cincinnati	Ohio
United States	Morton Plant Hospital	Clearwater	Florida
United States	Billings Clinic-Cody	Cody	Wyoming
United States	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho
United States	UCHealth Memorial Hospital Central	Colorado Springs	Colorado
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	UM Sylvester Comprehensive Cancer Center at Coral Gables	Coral Gables	Florida
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	UM Sylvester Comprehensive Cancer Center at Deerfield Beach	Deerfield Beach	Florida
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Illinois CancerCare-Dixon	Dixon	Illinois
United States	Miller-Dwan Hospital	Duluth	Minnesota
United States	Northeast Radiation Oncology Center	Dunmore	Pennsylvania
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Walter Knox Memorial Hospital	Emmett	Idaho
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Inova Schar Cancer Institute	Fairfax	Virginia
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Parkland Health Center - Farmington	Farmington	Missouri
United States	McLaren Cancer Institute-Flint	Flint	Michigan
United States	McFarland Clinic - Trinity Cancer Center	Fort Dodge	Iowa
United States	Mercy Hospital Fort Smith	Fort Smith	Arkansas
United States	Ascension Saint Francis - Reiman Cancer Center	Franklin	Wisconsin
United States	Unity Hospital	Fridley	Minnesota
United States	Fox Chase Cancer Center Buckingham	Furlong	Pennsylvania
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Banner Thunderbird Medical Center	Glendale	Arizona
United States	Glens Falls Hospital	Glens Falls	New York
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Saint Francis Cancer Center	Greenville	South Carolina
United States	Gibbs Cancer Center-Pelham	Greer	South Carolina
United States	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas
United States	M D Anderson Cancer Center	Houston	Texas
United States	Memorial Hermann Texas Medical Center	Houston	Texas
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	McFarland Clinic - Jefferson	Jefferson	Iowa
United States	Capital Region Southwest Campus	Jefferson City	Missouri
United States	NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro	Jonesboro	Arkansas
United States	Freeman Health System	Joplin	Missouri
United States	Mercy Hospital Joplin	Joplin	Missouri
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Karmanos Cancer Institute at McLaren Greater Lansing	Lansing	Michigan
United States	University of Kansas Cancer Center - Lee's Summit	Lee's Summit	Missouri
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	Saint Barnabas Medical Center	Livingston	New Jersey
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	Los Angeles County-USC Medical Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	Fairview Clinics and Surgery Center Maple Grove	Maple Grove	Minnesota
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	McFarland Clinic - Marshalltown	Marshalltown	Iowa
United States	Baptist Memorial Hospital and Cancer Center-Memphis	Memphis	Tennessee
United States	Idaho Urologic Institute-Meridian	Meridian	Idaho
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Ascension Columbia Saint Mary's Hospital - Milwaukee	Milwaukee	Wisconsin
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Health Partners Inc	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Community Medical Hospital	Missoula	Montana
United States	Monticello Cancer Center	Monticello	Minnesota
United States	McLaren Cancer Institute-Macomb	Mount Clemens	Michigan
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Saint Alphonsus Cancer Care Center-Nampa	Nampa	Idaho
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Yale University	New Haven	Connecticut
United States	Cancer Center of Western Wisconsin	New Richmond	Wisconsin
United States	New Ulm Medical Center	New Ulm	Minnesota
United States	Mount Sinai Chelsea	New York	New York
United States	Mount Sinai Hospital	New York	New York
United States	Mount Sinai West	New York	New York
United States	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	University of Kansas Cancer Center at North Kansas City Hospital	North Kansas City	Missouri
United States	Ascension Providence Hospitals - Novi	Novi	Michigan
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Upstate Cancer Center Radiation Oncology at Oneida	Oneida	New York
United States	Saint Alphonsus Medical Center-Ontario	Ontario	Oregon
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas
United States	University of Kansas Hospital-Indian Creek Campus	Overland Park	Kansas
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	OSF Saint Francis Radiation Oncology at Peoria Cancer Center	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Valley Radiation Oncology	Peru	Illinois
United States	McLaren Cancer Institute-Northern Michigan	Petoskey	Michigan
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Banner-University Medical Center Phoenix	Phoenix	Arizona
United States	Mayo Clinic Hospital in Arizona	Phoenix	Arizona
United States	McLaren-Port Huron	Port Huron	Michigan
United States	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Fairview Northland Medical Center	Princeton	Minnesota
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Ascension All Saints Hospital	Racine	Wisconsin
United States	Beebe Health Campus	Rehoboth Beach	Delaware
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Mercy Hospital South	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Kootenai Cancer Clinic	Sandpoint	Idaho
United States	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania
United States	Maine Medical Center- Scarborough Campus	Scarborough	Maine
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	Missouri Baptist Outpatient Center-Sunset Hills	Sunset Hills	Missouri
United States	Southwest Illinois Health Services LLP	Swansea	Illinois
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Moffitt Cancer Center	Tampa	Florida
United States	Saint Joseph's Hospital/Children's Hospital-Tampa	Tampa	Florida
United States	Community Medical Center	Toms River	New Jersey
United States	University of Arizona Cancer Center-North Campus	Tucson	Arizona
United States	Carle Cancer Center	Urbana	Illinois
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Epic Care Cyberknife Center	Walnut Creek	California
United States	Mercy Hospital Washington	Washington	Missouri
United States	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin
United States	Aspirus Regional Cancer Center	Wausau	Wisconsin
United States	University of Cincinnati Cancer Center-West Chester	West Chester	Ohio
United States	Lexington Medical Center	West Columbia	South Carolina
United States	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Novant Health Forsyth Medical Center	Winston-Salem	North Carolina
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Fairview Lakes Medical Center	Wyoming	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From the time of randomization up to 2 years post radiation
Secondary	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.	At 9 months
Secondary	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.	At 9 months
Secondary	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.	At 9 months
Secondary	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.	At 12 months
Secondary	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.	At 12 months
Secondary	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.	At 12 months
Secondary	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.	Up to 24 months
Secondary	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.	Up to 24 months
Secondary	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.	Up to 24 months
Secondary	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.	Up to 24 months
Secondary	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.	Up to 5 years
Secondary	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).	Up to 24 months
Secondary	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).	At 24 months
Secondary	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.	Up to 24 months