This phase II trial studies how well whole brain radiation therapy with simultaneous integrated boost works in treating patients with solid tumors that have spread to the brain (brain metastases). Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Lowering the dose of radiation therapy to the areas of the whole brain with no visible tumor (whole brain radiation therapy) and radiation therapy to areas of the brain where tumors are known to be (simultaneous integrated boost), may help preserve cognitive function while still preventing new tumor growth in the brain.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03189381.
PRIMARY OBJECTIVE:
I. Evaluate two de-escalated whole brain radiation dose levels (in the setting of simultaneous integrated boost to gross lesions) with respect to in-brain distant control for brain metastases, defined as an in-brain failure rate outside of the planning target volume at 6 months of < 20%.
SECONDARY OBJECTIVES:
I. Evaluate treated lesion control at 6 months for brain metastases in the setting of a predetermined total biologically effective simultaneous integrated boost (SIB) dose as determined by radiographic progression within the planning target volume with fusion and overlay of follow-up magnetic resonance imaging (MRI)s.
II. Evaluate overall survival at 6 months for brain metastases in the setting of whole brain radiation therapy (WBRT) with SIB.
III. Evaluate changes in neurocognitive function after WBRT with SIB in the following domains: verbal learning and memory as assessed by the Hopkins Verbal Learning Test-Revised (HVLT-R).
IV. Evaluate changes in health-related quality of life as assessed by the Functional Assessment of Cancer Therapy with Brain Subscale (FACT-Br) after WBRT-SIB for brain metastases.
V. Evaluate changes in performance status as assessed by the Karnofsky performance status tool after WBRT-SIB for brain metastases.
VI. Evaluate adverse events after WBRT-SIB for brain metastases according to current Common Terminology Criteria for Adverse Events (CTCAE) criteria.
EXPLORATORY OBJECTIVES:
I. Identify potential biomarkers that might help us in the future to develop a blood or urine test that can be used to predict response to therapy and radiation therapy side effects for each individual patient.
II. Perform exploratory correlative analyses on blood and urine circulating tumor deoxyribonucleic acid (DNA) and micro ribonucleic acid (RNA) biomarkers with a focus on treated lesion control, in-brain distant control, and overall survival and their correlation to patient and treatment characteristics.
OUTLINE: Patients are assigned to 1 of 2 cohorts.
COHORT I: Patients undergo higher dose of WBRT with SIB over 10 days.
COHORT II: Patients undergo lower dose of WBRT with SIB over 8 days.
After completion of study treatment, patients are followed up at 1, 3, 6, and 12 months.
Lead OrganizationIndiana University/Melvin and Bren Simon Cancer Center
Principal InvestigatorKevin Shiue
