Anatomic Stage IV Breast Cancer AJCC v8Metastatic Breast CarcinomaMetastatic Digestive System CarcinomaMetastatic Lung Non-Small Cell CarcinomaMetastatic Malignant Neoplasm in the BrainMetastatic Malignant Solid NeoplasmMetastatic MelanomaMetastatic Renal Cell CarcinomaStage IV Lung Cancer AJCC v8Stage IV Renal Cell Cancer AJCC v8
This phase III trial compares the effectiveness of fractionated stereotactic radiosurgery (FSRS) to usual care stereotactic radiosurgery (SRS) in treating patients with cancer that has spread from where it first started to the brain. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. FSRS delivers a high dose of radiation to the tumor over 3 treatments. SRS is a type of external radiation therapy that uses special equipment to position the patient and precisely give a single large dose of radiation to a tumor. FSRS may be more effective compared to SRS in treating patients with cancer that has spread to the brain.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* Pathologically (histologically or cytologically) proven diagnosis of one of the following solid tumor malignancies within 5 years prior to registration:
* Non-small cell lung cancer
* Melanoma
* Breast cancer
* Renal cell carcinoma
* Gastrointestinal cancer
* If the original histologic proof of malignancy is greater than 5 years, then more recent pathologic confirmation (e.g., from a systemic site or brain metastasis) or unequivocal imaging confirmation of extracranial metastatic disease (e.g. CT of the chest/abdomen/pelvis, positron emission tomography \[PET\]/CT, etc.) is required
* Patients must have at least 1 and up to 8 total intact brain metastases detected on a contrast-enhanced MRI performed ≤ 21 days prior to registration
* At least 1 of the up to 8 lesions must be a study eligible lesion, defined as lesion with a maximum diameter as measured on any orthogonal plane (axial, sagittal, coronal) of ≥ 1.0 cm and ≤ 3.0 cm
* All brain metastases must be located outside of the brainstem and ≥ 5 mm from the optic nerves or optic chiasm and ≤ 3.0 cm in maximum dimension
* Note: brainstem metastases per the MRI within 21 days of registration are an exclusion criterion; however, if the MRI used for treatment planning performed within 7 days of SRS/FSRS reveals a brainstem metastasis, the patient remains eligible if the patient is considered an appropriate radiosurgery candidate per the local investigator
* Patients must have a diagnosis-specific graded prognostic assessment ≥ 1.5
* No more than 2 lesions planned for resection if clinically indicated
* No known leptomeningeal disease (LMD)
* Note: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive cerebrospinal fluid (CSF) cytology and/or unequivocal 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. 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
* Age ≥ 18 years
* Karnofsky performance status (KPS) ≥ 60
* Negative urine or serum pregnancy test (in persons of childbearing potential) 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 postmenopausal
* No prior radiotherapy to the brain (partial or whole brain irradiation, SRS, FSRS, or prophylactic cranial irradiation \[PCI\])
* New York Heart Association Functional Classification II or better (NYHA Functional Classification III/IV are not eligible) (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification)
* No active infection currently requiring intravenous (IV) antibiotic management
* No hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
* No chronic obstructive pulmonary disease exacerbation or other acute respiratory illness precluding study therapy
Primary outcome measure(s)
Time to local failure — From randomization (with the treatment planning magnetic resonance imaging as the 'baseline' for purposes of disease assessment) to local tumor progression of any study lesion(s), assessed up to 5 years The time to local failure will be evaluated at a per-patient level. The cause-specific hazard ratio will be estimated in a Cox proportional hazards (PH) model adjusting for patients and disease characteristics. The Cox PH model will be the principle approach. The cumulative incidence function estimator will also be used to estimate the rate of local failure in the presence of competing event of deaths in the two arms separately. A complementary analysis will involve Gray's test to evaluate the difference in the distribution of local failure between treatment arms. These results will be interpreted in light of the competing deaths.
Trial sites (270)
Facility
City
Region
Status
Banner University Medical Center - Tucson
Tucson
Arizona
University of Arizona Cancer Center-North Campus
Tucson
Arizona
Mercy Hospital Fort Smith
Fort Smith
Arkansas
University of Arkansas for Medical Sciences
Little Rock
Arkansas
Kaiser Permanente-Anaheim
Anaheim
California
Kaiser Permanente-Bellflower
Bellflower
California
City of Hope Corona
Corona
California
City of Hope Comprehensive Cancer Center
Duarte
California
UC San Diego Health System - Encinitas
Encinitas
California
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine
California
City of Hope at Irvine Lennar
Irvine
California
UC San Diego Moores Cancer Center
La Jolla
California
City of Hope Antelope Valley
Lancaster
California
Kaiser Permanente Los Angeles Medical Center
Los Angeles
California
Cedars-Sinai Medical Center
Los Angeles
California
Providence Queen of The Valley
Napa
California
Kaiser Permanente-Ontario
Ontario
California
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange
California
Stanford Cancer Institute Palo Alto
Palo Alto
California
UC San Diego Medical Center - Hillcrest
San Diego
California
Providence Medical Foundation - Santa Rosa
Santa Rosa
California
City of Hope South Pasadena
South Pasadena
California
City of Hope South Bay
Torrance
California
City of Hope Upland
Upland
California
John Muir Medical Center-Walnut Creek
Walnut Creek
California
UCHealth University of Colorado Hospital
Aurora
Colorado
UCHealth Memorial Hospital Central
Colorado Springs
Colorado
Memorial Hospital North
Colorado Springs
Colorado
Poudre Valley Hospital
Fort Collins
Colorado
Cancer Care and Hematology-Fort Collins
Fort Collins
Colorado
UCHealth Greeley Hospital
Greeley
Colorado
Medical Center of the Rockies
Loveland
Colorado
Hartford Hospital
Hartford
Connecticut
The Hospital of Central Connecticut
New Britain
Connecticut
UM Sylvester Comprehensive Cancer Center at Aventura
Aventura
Florida
Boca Raton Regional Hospital
Boca Raton
Florida
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables
Florida
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach
Florida
UM Sylvester Comprehensive Cancer Center at Doral
Doral
Florida
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami
Florida
+ 230 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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