Brief Summary

This phase III trial compares the usual treatment of surgery after stereotactic radiosurgery (SRS) to receiving SRS before surgery in treating patients with cancer that has spread to the brain (brain metastases). Stereotactic radiosurgery is a type of radiation therapy that delivers a high dose of radiation to target tumors and minimizes effect on normal surrounding brain tissue. The combination of surgery and radiation may stop the tumor from growing for a few months or longer and may reduce symptoms of brain metastases. This study investigates whether treating with SRS before surgery may be better than SRS after surgery in reducing the possibility of the tumor coming back, reducing or preventing the cancer from spreading to other areas of the brain and reducing the risk of scarring on the brain from radiation.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

237

participants targeted

Target at P50-P75 for phase_3

Timeline

10mo left

Started Oct 2022

Typical duration for phase_3

Geographic Reach

3 countries

216 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

4.4 years study duration

Study Progress81%

Oct 2022Mar 2027

First Submitted

Initial submission to the registry

June 24, 2022

Completed

5 days until next milestone

First Posted

Study publicly available on registry

June 29, 2022

Completed

4 months until next milestone

Study Start

First participant enrolled

October 24, 2022

Completed

4.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 16, 2027

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 16, 2027

Last Updated

May 7, 2026

Status Verified

April 1, 2026

Enrollment Period

4.4 years

First QC Date

June 24, 2022

Last Update Submit

May 5, 2026

Conditions

Metastatic Malignant Neoplasm in the Brain

Outcome Measures

Primary Outcomes (1)

Time to composite adverse endpoint (CAE)
Analysis for this endpoint will consist of testing the cause-specific hazard ratio in a Cox proportional hazards model.
Time from surgery (with the post-operative MRI as the 'baseline' for purposes of disease assessment) to local tumor progression (within the surgical bed), nodular meningeal disease, or radiation necrosis, whichever occurs first, assessed up to 4 years

Secondary Outcomes (8)

Overall survival (OS)
Time from randomization to death due to any cause, assessed up to 4 years
Rate of local tumor progression
Up to 4 years
Rate of radiation necrosis
Up to 4 years
Rate of nodular meningeal disease
Up to 4 years
Rate of distant brain failures
Up to 4 years
+3 more secondary outcomes

Other Outcomes (1)

Type of surgical resection
Up to 4 years

Study Arms (2)

Arm I (surgery, stereotactic radiosurgery)

ACTIVE COMPARATOR

Patients undergo surgery per standard of care. Within 10-30 days after surgery, patients undergo stereotactic radiosurgery for 1 fraction.

Procedure: Brain SurgeryOther: Quality-of-Life AssessmentOther: Questionnaire AdministrationRadiation: Stereotactic Radiosurgery

Arm II (stereotactic radiosurgery, surgery)

EXPERIMENTAL

Within 7 days before surgery, patients undergo stereotactic radiosurgery for 1 fraction. Patients undergo surgery per standard of care.

Procedure: Brain SurgeryOther: Quality-of-Life AssessmentOther: Questionnaire AdministrationRadiation: Stereotactic Radiosurgery

Interventions

Brain SurgeryPROCEDURE

Undergo surgery per standard of care

Arm I (surgery, stereotactic radiosurgery)Arm II (stereotactic radiosurgery, surgery)

Quality-of-Life AssessmentOTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm I (surgery, stereotactic radiosurgery)Arm II (stereotactic radiosurgery, surgery)

Questionnaire AdministrationOTHER

Ancillary studies

Arm I (surgery, stereotactic radiosurgery)Arm II (stereotactic radiosurgery, surgery)

Stereotactic RadiosurgeryRADIATION

Undergo stereotactic radiosurgery

Also known as: SRS, Stereotactic External Beam Irradiation, stereotactic external-beam radiation therapy, Stereotactic Radiation Therapy, Stereotactic Radiotherapy, stereotaxic radiation therapy, stereotaxic radiosurgery

Arm I (surgery, stereotactic radiosurgery)Arm II (stereotactic radiosurgery, surgery)

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Radiographic confirmation of 1-4 brain metastases, one of which requires resection, as defined by magnetic resonance imaging (MRI) with contrast obtained within 14 days prior to registration
The maximum diameter of the lesion to be resected on the post-contrast MRI, as measured on any orthogonal plane (axial, sagittal, coronal), must measure \>= 2.0 cm and =\< 5.0 cm.
The maximum diameter of any lesions which will not be resected must be =\< 4.0 cm in maximum diameter
Known active or history of invasive non-central nervous system (CNS) primary cancer based on documented pathologic diagnosis within the past 3 years
All brain metastases must be located \>= 5 mm from the optic chiasm and outside the brainstem
Patient is able to medically tolerate surgery and SRS
Lesions chosen for surgical therapy must be deemed appropriate targets for safe, gross total resection by the treating surgeon
History/physical examination within 14 days prior to registration
Age \>= 18
Karnofsky performance status (KPS) \>= 60 within 14 days prior to registration
A 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
Participants who are sexually active must agree to use medically acceptable forms of contraception during treatment on this study to prevent pregnancy
The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information

You may not qualify if:

Prior cranial radiotherapy, including whole brain radiotherapy, or SRS to the resection site
Note: The index lesion to be resected cannot have been previously treated with SRS (i.e. repeat radiosurgery to the same location/lesion is not allowed on this protocol). Previous SRS to other lesions is allowed
Evidence of leptomeningeal disease (LMD)
Any medical conditions which would make this protocol unreasonably hazardous, including, but not limited to: contraindications to general endotracheal anesthesia; intracranial surgery; and stereotactic radiosurgery
Primary histology of germ cell tumor, small cell carcinoma or lymphoma
More than one brain metastasis planned for resection
Inability to undergo MRI with contrast
Planned administration of cytotoxic chemotherapy or tyrosine/multi-kinase inhibitors within the 3 days prior to, the day of, or within 3 days after the completion of SRS
Note: chemotherapy and immunotherapy outside of this window are allowed

Contact the study team to confirm eligibility.

Sponsors & Collaborators

NRG Oncologylead
National Cancer Institute (NCI)collaborator

Study Sites (216)

Saint Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013, United States

Location

Banner University Medical Center - Tucson

Tucson, Arizona, 85719, United States

Location

University of Arizona Cancer Center-North Campus

Tucson, Arizona, 85719, United States

Location

Kaiser Permanente-Anaheim

Anaheim, California, 92806, United States

Location

Sutter Auburn Faith Hospital

Auburn, California, 95602, United States

Location

Sutter Cancer Centers Radiation Oncology Services-Auburn

Auburn, California, 95603, United States

Location

Kaiser Permanente-Bellflower

Bellflower, California, 90706, United States

Location

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

Irvine, California, 92612, United States

Location

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, 90027, United States

Location

Memorial Medical Center

Modesto, California, 95355, United States

Location

Kaiser Permanente-Ontario

Ontario, California, 91761, United States

Location

Saint Joseph Hospital - Orange

Orange, California, 92868, United States

Location

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

Stanford Cancer Institute Palo Alto

Palo Alto, California, 94304, United States

Location

Sutter Cancer Centers Radiation Oncology Services-Roseville

Roseville, California, 95661, United States

Location

Sutter Roseville Medical Center

Roseville, California, 95661, United States

Location

Sutter Medical Center Sacramento

Sacramento, California, 95816, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

California Pacific Medical Center-Pacific Campus

San Francisco, California, 94115, United States

Location

UCSF Medical Center-Parnassus

San Francisco, California, 94143, United States

Location

Sutter Pacific Medical Foundation

Santa Rosa, California, 95403, United States

Location

Sutter Solano Medical Center/Cancer Center

Vallejo, California, 94589, United States

Location

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, 33146, United States

Location

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, 33442, United States

Location

UM Sylvester Comprehensive Cancer Center at Doral

Doral, Florida, 33166, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

Miami Cancer Institute

Miami, Florida, 33176, United States

Location

UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida, 33324, United States

Location

Moffitt Cancer Center-International Plaza

Tampa, Florida, 33607, United States

Location

Moffitt Cancer Center - McKinley Campus

Tampa, Florida, 33612, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Moffitt Cancer Center at Wesley Chapel

Wesley Chapel, Florida, 33544, United States

Location

Grady Health System

Atlanta, Georgia, 30303, United States

Location

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Piedmont Hospital

Atlanta, Georgia, 30309, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Emory Saint Joseph's Hospital

Atlanta, Georgia, 30342, United States

Location

Hawaii Cancer Care Inc - Waterfront Plaza