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Comparing two types of radiation therapy for brain cancer from other cancers

Phase III Trial of Single Fraction Stereotactic Radiosurgery (SRS) Versus Fractionated SRS (FSRS) for Intact Brain Metastases

Phase 3 Interventional NRG Oncology · NCT06500455

This study is testing whether a new way of giving radiation therapy in multiple sessions can help people with brain cancer from other cancers do better than the standard single-session treatment.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment269 (estimated)
Ages18 Years and up
SexAll
SponsorNRG Oncology Academic / other
Drugs / interventionsRadiation
Locations263 sites (Tucson, Arizona and 262 other locations)
Trial IDNCT06500455 on ClinicalTrials.gov

What this trial studies

This phase III trial evaluates the effectiveness of fractionated stereotactic radiosurgery (FSRS) compared to standard stereotactic radiosurgery (SRS) in patients with brain metastases from various cancers. Patients will be randomized into two groups: one receiving SRS in a single session and the other receiving FSRS over three sessions. The study aims to determine if FSRS leads to better outcomes in terms of local failure, intracranial progression-free survival, and overall survival. Additionally, it will assess differences in failure patterns and rates of adverse events between the two treatment approaches.

Who should consider this trial

Good fit: Ideal candidates include patients with pathologically confirmed solid tumors that have metastasized to the brain, specifically those with 1 to 8 intact brain metastases.

Not a fit: Patients with brain metastases that are not intact or those with certain types of cancers not included in the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more effective radiation therapy option for patients with brain metastases, potentially improving survival and quality of life.

How similar studies have performed: Other studies have shown promising results with stereotactic radiosurgery approaches, but the specific comparison of FSRS to SRS in this context is novel.

Eligibility criteria

Show full inclusion / exclusion criteria 
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

Where this trial is running

Tucson, Arizona and 262 other locations

+213 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions 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 Carcinoma
Last reviewed 2026-06-10 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.