Testing Longer Duration Radiation Therapy Versus the Usual Radiation Therapy in Patients With Cancer That Has Spread to the Brain
NCT Number: NCT06500455
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: Anatomic Stage IV Breast Cancer AJCC v8|Clinical Stage IV Cutaneous Melanoma 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
Interventions: PROCEDURE: Computed Tomography|RADIATION: Fractionated Stereotactic Radiation Therapy|PROCEDURE: Magnetic Resonance Imaging|RADIATION: Stereotactic Radiosurgery
Sponsor: NRG Oncology
Collaborators: National Cancer Institute (NCI)
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 269
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08-30
Completion Date: 2033-06-30

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.

Primary Outcome Measures: Time to local failure, 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., 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
Secondary Outcome Measures: Intracranial progression-free survival (IPFS), IPFS 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., From the date of randomization until intracranial progression (local or distant intracranial) or death from any cause, whichever occurs first, assessed up to 5 years|Overall survival, Will 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., From the date of randomization until death from any cause, assessed up to 5 years|Time to radiation necrosis (TTRN), The 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)., From randomization until radiation necrosis, assessed up to 5 years|Time to whole brain radiation therapy (WBRT), Analysis 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., Up to 5 years|Incidence of adverse events (AEs), AEs 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., Up to 2 years from start of radiation treatment
Other Outcome Measures: Time to local failure, Estimates of the primary outcome treatment effect and the corresponding 95% confidence interval will be provided by sex, race, and ethnicity., Up to 5 years