RATIONALE: Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. PURPOSE: This phase II trial is studying how well sunitinib malate works after stereotactic radiosurgery in treating patients with newly diagnosed brain metastases.
OBJECTIVES: Primary * Determine the CNS progression-free survival rate in patients with 1-3 newly diagnosed brain metastases treated with sunitinib malate after stereotactic radiosurgery (SRS). Secondary * Determine the rate of local (site of SRS treatment) failure at 12 months in these patients. * Determine the median time to CNS disease progression in these patients. * Determine the overall survival of these patients. * Determine the time to progression of systemic disease in these patients. * Evaluate the safety of sunitinib malate when administered after SRS in these patients. * Assess the neurocognitive effects of SRS followed by sunitinib malate in these patients. OUTLINE: Patients receive oral sunitinib malate once daily on days 1-28. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity. Patients undergo neuropsychological battery testing at baseline and periodically during study to assess cognitive function (memory, verbal fluency, visual-motor speed, executive function, and motor dexterity), activities of daily living, and quality of life.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
14
Treatment will be administered on an outpatient basis. Patients will receive sunitinib 37.5mg once daily in the morning without regard to meals in repeated 6-week cycles comprising daily therapy for 4 weeks followed by a 2-week rest period. Patients who tolerate this dose may increase the dose to 50 mg once daily.
The memory test has six alternate forms. The other tests measure motor and information processing speed and are relatively resistant to the effects of practice. The total time for test administration, including the QOL and symptom measures, is 40 minutes.The difference between the pre-treatment baseline and follow-up assessment scores will be determined by the reliable change (RC) index. This index is derived from the standard error of measurement (SEM) for each test in the battery: 1 (deterioration), 2 (no change), or and 3 (improved).
Henry Ford Health System
Detroit, Michigan, United States
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States
Central Nervous System (CNS) Progression-free Survival Rate
The number of subjects surviving at least six months from SRS without progressive disease anywhere in the brain (local or regional failure), assessed by the McDonald's standard criteria.Progressive neurologic abnormalities not explained by causes unrelated to tumor progression (e.g. anticonvulsant or corticosteroid toxicity, electrolyte abnormalities, hyperglycemia, etc.) or a greater than 25% increase in the size of the tumor by MRI/CT scan.
Time frame: 6 months after stereotactic radiosurgery (SRS)
Central Nervous System (CNS) Progression-free Survival Rate
The number of subjects surviving at least 12 months from SRS without progressive disease anywhere in the brain (local or regional failure), assessed by the McDonald's standard criteria. Progressive neurologic abnormalities not explained by causes unrelated to tumor progression (e.g. anticonvulsant or corticosteroid toxicity, electrolyte abnormalities, hyperglycemia, etc.) or a greater than 25% increase in the size of the tumor by MRI/CT scan.
Time frame: 12 months after stereotactic radiosurgery (SRS)
Median Time to CNS Disease Progression
Time to disease progression will be recorded from the first day of protocol therapy until the criteria for disease progression are met, patient death from any cause or removal of the patient from study for any reason, whichever comes first.
Time frame: up to12 months from SRS
Overall Survival
The number of subjects surviving at least 12 months from stereotactic radiosurgery.
Time frame: 12 months from SRS
Time to Progression
Time to progression (all sites of disease) - interval between stereotactic radiosurgery and the earliest date of progression (systemic or CNS) or death due to any cause.
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Time frame: at 3 yrs from SRS
Rate of Local Failure at 12 Months
Rate of local vs regional failure -rates of progression at site of stereotactic radiosurgery (local failure)vs progression anywhere else in CNS (regional failure).
Time frame: 12 months
Neurocognitive Effects
The number of patients that had statistically significant change (p's \> 0.05) in their neurocognitive assessment (improvement or decline) from baseline. Neurocognitive function was assessed in several domains, including memory, verbal fluency, visual-motor speed, executive function and motor dexterity.The difference between the pre-treatment baseline and follow-up assessment scores were determined by the reliable change (RC) index. RC Index: 1=deterioration, 2=no change, 3=improved
Time frame: at 2 months after treatment
Safety and Tolerability
Number of patients that experienced treatment-related G 3-4 adverse events.
Time frame: 3 years from study start