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Testing Longer Duration Radiation Therapy Versus the Usual Radiation Therapy in Patients With Cancer That Has Spread to the Brain

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

Status
Recruiting
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT06500455
Enrollment
269
Registered
2024-07-15
Start date
2024-12-12
Completion date
2028-06-30
Last updated
2026-04-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Breast Carcinoma, Metastatic Digestive System Carcinoma, Metastatic Lung Non-Small Cell Carcinoma, Metastatic Malignant Neoplasm in the Brain, Metastatic Malignant Solid Neoplasm, Metastatic Melanoma, Metastatic Renal Cell Carcinoma, Stage IV Lung Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8

Brief summary

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.

Detailed description

PRIMARY OBJECTIVE: I. To determine if the time to local failure is improved with FSRS compared to SRS in patients with intact (i.e., unresected) brain metastases. SECONDARY OBJECTIVES: I. To compare time to intracranial progression-free survival between FSRS and SRS. II. To compare overall survival between FSRS and SRS. III. To determine if the time to local failure is improved with FSRS compared to SRS, as evaluated by central review of imaging. IV. To evaluate if there is any difference in central nervous system (CNS) failure patterns (local versus \[vs.\] distant brain failure vs. both) in patients who receive FSRS compared to patients who receive SRS. V. To compare the rates of radiation necrosis in patients who receive FSRS vs. SRS. VI. To compare the time to salvage whole brain radiation therapy (WBRT) between patients who receive FSRS and those who receive SRS. VII. To compare the rates of post-treatment adverse events associated with FSRS and SRS. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients undergo SRS over 30-90 minutes for 1 fraction on study. Additionally, patients undergo computed tomography (CT) and magnetic resonance imaging (MRI) on study. ARM II: Patients undergo FSRS over 30-90 minutes for 3 fractions on study. Additionally, patients undergo CT and MRI on study. After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year then every 6 months for 3 years.

Interventions

PROCEDUREComputed Tomography

Undergo CT

PROCEDUREMagnetic Resonance Imaging

Undergo MRI

RADIATIONStereotactic Radiosurgery

Undergo SRS

Sponsors

NRG Oncology
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
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

Design outcomes

Primary

MeasureTime frameDescription
Time to local failureFrom 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 yearsThe 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.

Secondary

MeasureTime frameDescription
Intracranial progression-free survival (IPFS)From the date of randomization until intracranial progression (local or distant intracranial) or death from any cause, whichever occurs first, assessed up to 5 yearsIPFS will consist of estimation of its distribution for each treatment arm via the Kaplan-Meier method and a stratified log-rank test. Statistical power will depend on the total IPFS events accumulated at trial end.
Overall survivalFrom the date of randomization until death from any cause, assessed up to 5 yearsWill consist of estimation of its distribution for each treatment arm via the Kaplan-Meier method and a stratified log-rank test. Reasons for death (e.g. due to neurological cause \[any central nervous system event such as an intracranial mass, hemorrhage, or hydrocephalus\] or non-neurological cause) will be recorded.
Time to radiation necrosis (TTRN)From randomization until radiation necrosis, assessed up to 5 yearsThe rate of radiation necrosis will be compared in patients who receive fractionated stereotactic radiosurgery to patients who receive stereotactic radiosurgery. The primary comparison of treatment effect on TTRN will be based on testing the cause-specific hazard ratio (CHR) in a univariate Cox proportional hazards model. Additional supplementary analyses will include estimating the cause specific ratio in a Cox proportional hazards model adjusting for patients and disease characteristics (e.g. stratification randomization factors) and estimating the median TTRN via the cumulative incidence function estimator (Korn 1992). The Gray's test will also be used to evaluate the difference in the distribution of TTRN between treatment arms (Gray 1988).
Time to whole brain radiation therapy (WBRT)Up to 5 yearsAnalysis of time to WBRT will consist of estimation of its distribution for each treatment arm via the Kaplan-Meier method and a stratified log-rank test. For patients who die prior to WBRT, time to WBRT will be censored at time of death.
Incidence of adverse events (AEs)Up to 2 years from start of radiation treatmentAEs will be graded according to Common Terminology Criteria in Adverse Events version 5.0. Comprehensive summaries of all AEs by treatment arm will be generated and examined. Counts and frequencies of worst AE per patients will be presented overall and by AE type category, separately by assigned treatment group. The proportion of patients with at least one grade 3 or higher AE will be compared between arms. Frequencies for specific potentially treatment related AEs where grade 3 or higher events are noted may be compared. Any frequencies to be tested will be evaluated using the chi-square or exact test as appropriate, with two-sided significance level of 0.05.

Countries

Canada, Hong Kong, Ireland, United States

Contacts

PRINCIPAL_INVESTIGATORRupesh R Kotecha

NRG Oncology

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Apr 4, 2026