Home
Clinical Trials
NCT05438212

Comparing the Addition of Radiation Either Before or After Surgery for Patients With Brain Metastases

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

237 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-10-24

Study Completion Date

2027-03-16

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

PRIMARY OBJECTIVE:

I. To determine if the time to composite adverse endpoint (CAE) (defined as: 1) local tumor progression within the surgical bed; and/or 2) adverse radiation effect \[ARE\], the imaging correlate of post-stereotactic radiosurgery \[SRS\] radiation necrosis; and/or 3) nodular meningeal disease \[nMD\]) is improved in patients treated with pre-resection SRS to the intact lesion versus those treated with post-resection SRS.

SECONDARY OBJECTIVES:

I. To assess the trajectory of symptom burden in patients treated with pre-resection SRS to the intact lesion versus those treated to the post-resection surgical cavity as measured by MD Anderson Symptom Inventory for brain tumor (MDASI-BT).

II. To determine whether there is improved overall survival (OS) in patients with resected brain metastases who undergo pre-resection SRS compared to patients who receive post-resection SRS.

III. To compare rates of ARE, the imaging correlate of radiation necrosis, in patients who receive pre-resection SRS to patients who receive post-resection SRS.

IV. To determine whether there is increased time to whole brain radiotherapy (WBRT) in patients who receive pre-resection SRS compared to patients who receive post-resection SRS.

V. To assess the trajectory of neuro-cognitive function in patients treated with pre-resection SRS to the intact lesion versus those treated to the post-resection surgical cavity as measured by the Montreal Cognitive Assessment (MoCA).

VI. To compare rates of nodular meningeal disease in patients who receive pre-resection SRS to patients who receive post-resection SRS.

VII. To compare rates of local recurrence in the resection cavity for patients who receive pre-resection SRS to patients who receive post-resection SRS.

VIII. To compare rates of local recurrence of intact, non-index metastases treated with SRS.

IX. To compare rates of distant brain failure in patients who receive pre-resection SRS to patients who receive post-resection SRS.

X. To assess toxicity in the two treatment arms.

EXPLORATORY OBJECTIVE:

I. To explore if the type of surgical resection (piece-meal versus \[vs.\] en-bloc) may be associated with the rate of nodular meningeal disease.

OUTLINE: Patients are randomized to 1 of 2 arms.

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

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

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for additional 2 years.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Metastatic Malignant Neoplasm in the Brain

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Arm I (surgery, stereotactic radiosurgery)

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

Group Type ACTIVE_COMPARATOR

Brain Surgery

Intervention Type PROCEDURE

Undergo surgery per standard of care

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Stereotactic Radiosurgery

Intervention Type RADIATION

Undergo stereotactic radiosurgery

Arm II (stereotactic radiosurgery, surgery)

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

Group Type EXPERIMENTAL

Brain Surgery

Intervention Type PROCEDURE

Undergo surgery per standard of care

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Stereotactic Radiosurgery

Intervention Type RADIATION

Undergo stereotactic radiosurgery

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Brain Surgery

Undergo surgery per standard of care

Intervention Type PROCEDURE

Quality-of-Life Assessment

Ancillary studies

Intervention Type OTHER

Questionnaire Administration

Ancillary studies

Intervention Type OTHER

Stereotactic Radiosurgery

Undergo stereotactic radiosurgery

Intervention Type RADIATION

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Quality of Life Assessment SRS Stereotactic External Beam Irradiation stereotactic external-beam radiation therapy Stereotactic Radiation Therapy Stereotactic Radiotherapy stereotaxic radiation therapy stereotaxic radiosurgery

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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

Exclusion Criteria

* 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)

* 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
* 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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Stuart H Burri

Role: PRINCIPAL_INVESTIGATOR

NRG Oncology

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Saint Joseph's Hospital and Medical Center

Phoenix, Arizona, United States

Site Status

Banner University Medical Center - Tucson

Tucson, Arizona, United States

Site Status

University of Arizona Cancer Center-North Campus

Tucson, Arizona, United States

Site Status

Kaiser Permanente-Anaheim

Anaheim, California, United States

Site Status

Sutter Auburn Faith Hospital

Auburn, California, United States

Site Status

Sutter Cancer Centers Radiation Oncology Services-Auburn

Auburn, California, United States

Site Status

Kaiser Permanente-Bellflower

Bellflower, California, United States

Site Status

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

Irvine, California, United States

Site Status

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, United States

Site Status

Memorial Medical Center

Modesto, California, United States

Site Status

Kaiser Permanente-Ontario

Ontario, California, United States

Site Status

Saint Joseph Hospital - Orange

Orange, California, United States

Site Status

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, United States

Site Status

Stanford Cancer Institute Palo Alto

Palo Alto, California, United States

Site Status

Sutter Cancer Centers Radiation Oncology Services-Roseville

Roseville, California, United States

Site Status

Sutter Roseville Medical Center

Roseville, California, United States

Site Status

Sutter Medical Center Sacramento

Sacramento, California, United States

Site Status

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

Site Status

California Pacific Medical Center-Pacific Campus

San Francisco, California, United States

Site Status

UCSF Medical Center-Parnassus

San Francisco, California, United States

Site Status

Sutter Pacific Medical Foundation

Santa Rosa, California, United States

Site Status

Sutter Solano Medical Center/Cancer Center

Vallejo, California, United States

Site Status

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, United States

Site Status

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, United States

Site Status

UM Sylvester Comprehensive Cancer Center at Doral

Doral, Florida, United States

Site Status

Mayo Clinic in Florida

Jacksonville, Florida, United States

Site Status

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

Site Status

Miami Cancer Institute

Miami, Florida, United States

Site Status

UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida, United States

Site Status

Moffitt Cancer Center-International Plaza

Tampa, Florida, United States

Site Status

Moffitt Cancer Center - McKinley Campus

Tampa, Florida, United States

Site Status

Moffitt Cancer Center

Tampa, Florida, United States

Site Status

Moffitt Cancer Center at Wesley Chapel

Wesley Chapel, Florida, United States

Site Status

Grady Health System

Atlanta, Georgia, United States

Site Status

Emory University Hospital Midtown

Atlanta, Georgia, United States

Site Status

Piedmont Hospital

Atlanta, Georgia, United States

Site Status

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States

Site Status