Hippocampal Sparing Whole Brain Radiation Versus Stereotactic Radiation in Patients With 5-20 Brain Metastases: A Phase III, Randomized Trial

Study Overview
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Brief Summary
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This research study is studying two different types of radiation as treatment for brain metastases (tumors in the brain that spread from a cancer that originated elsewhere in the body)

Detailed Description
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This research study is a Phase III clinical trial. Phase III clinical trials examine the safety and effectiveness of a treatment, often comparing it to another known treatment. In this case, the investigators are specifically looking at differences between two forms of radiation treatment in terms of subsequent quality of life. In this research study, the investigators are comparing stereotactic (focused, pinpoint) radiation (in which each tumor is narrowly targeted) against whole brain radiation (radiation targeting the entire brain) in the treatment of brain metastases. Currently whole brain radiation is the standard option for patients with 5-20 brain metastases. Stereotactic radiation is the standard option for patients with 1-4 brain metastases. Among patients with 1-4 brain metastases, recently published studies suggest that stereotactic radiation results in fewer neurologic side effects than whole brain radiation. It also yields better quality of life in this population. It remains unknown whether stereotactic radiation improves quality of life in patients with 5-20 brain metastases relative to whole brain radiation. In this study, the investigators seek to determine which of the two methods of study treatment results in a better subsequent quality of life for patients with 5-20 brain metastases.

Official Title
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Hippocampal Sparing Whole Brain Radiation Versus Stereotactic Radiation (SRS) in Patients With 5-20 Brain Metastases: A Phase III, Randomized Clinical Trial

Conditions
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Brain Metastases

Intervention / Treatment
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* Radiation: Whole brain radiation
* Radiation: Stereotactic radiation (SRS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have a biopsy proven solid malignancy with untreated (by radiation) intracranial lesions radiographically consistent with or pathologically proven to be brain metastases. Patients who have undergone prior systemic therapy are eligible Five-twenty intracranial lesions must be present on MRI of the brain Age 18-80 years at diagnosis of brain metastases Karnofsky performance status of at least 70 Exclusion Criteria: Participants who have undergone prior radiation for brain metastases. Patients who have undergone resection of one or more brain metastases but who have not yet started adjuvant radiotherapy are eligible for the study Participants who cannot undergo a brain MRI Participants who cannot receive gadolinium (MRI contrast) Participants with stage IV-V chronic kidney disease or end stage renal disease Participants with widespread, definitive leptomeningeal disease Participants with small cell lung cancer, lymphoma, or myeloma Participants with a maximum tumor diameter exceeding 5 cm (if not resected)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Whole Brain Radiation<br>MRI will be performed prior to radiation is administered A hippocampal sparing approach will be used when possible Dose will be 30 Gy in 10 fractions | Radiation: Whole brain radiation<br>* Treatment of the whole brain with radiation. When possible the hippocampus will be spared from radiation.<br>|
| Experimental: Stereotactic Radiation (SRS)<br>MRI will be performed prior to radiation is administered Radiation will be given in 1-5 fractions (dose depends on the size of the tumor that will be treated) | Radiation: Stereotactic radiation (SRS)<br>* Focused radiation to each individual brain metastasis without treatment of the remainder of the brain.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life Survey (symptoms and interference) | Questionnaire - MD Anderson Symptom Inventory - Brain Tumor (MDASI-BT) | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Clinical Parameter | Through study completion, an average of 1 year | 
| Neurologic survival | Clinical parameter to be assessed via review of study visits and medical records indicating cause of death (neurologic versus systemic) | Through study completion, an average of 1 year | 
| Incidence and time to detection of new brain metastases | Radiographic assessment of first appearance of new brain metastases | Through study completion, an average of 1 year | 
| Incidence and time to local recurrence of treated brain tumor(s) | Radiographic assessment of first local recurrence in the 5-20 brain metastases that were initially treated with radiation | Through study completion, an average of 1 year | 
| Incidence and time to development of radiation necrosis | Radiographic assessment of first appearance of radiation necrosis | Through study completion, an average of 1 year | 
| Incidence and time to development of leptomeningeal disease | Radiographic assessment of first appearance of leptomeningeal disease | Through study completion, an average of 1 year | 
| Incidence and time to salvage craniotomy | Clinical assessment of first use of neurosurgical resection as salvage therapy | Through study completion, an average of 1 year | 
| Incidence and time to additional radiotherapeutic treatments | Clinical assessment of first use of salvage brain-directed radiation | Through study completion, an average of 1 year | 
| Incidence and time to the development of seizures | Clinical assessment of first post-treatment seizure as assessed during routine study visits and via medical record review | Through study completion, an average of 1 year | 
| Incidence and time to neurocognitive decline | Scale | 1 year | 
| Performance status | Questionnaire - Karnofsky performance status | Through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Brain metastases, Brain metastasis, Lung cancer, Melanoma, Breast cancer, Kidney cancer, Renal cell carcinoma, Stereotactic radiation, Stereotactic radiosurgery, SRS, Stereotactic, Whole brain radiation, WBRT, Hippocampal avoidance, Hippocampal sparing, Hippocampal, Hippocampus, Radiation, Quality of Life, Neurocognitive, Neurocognition, Survival, Salvage, MDASI, Chemotherapy, Recurrence