Memantine in Preventing Side Effects in Patients Undergoing Whole-Brain Radiation Therapy for Brain Metastases From Solid Tumors

• Cognitive function, specifically memory, 24 weeks from the start of drug treatment as measured by the Hopkins Verbal Learning Test-Revised for delayed recall (HVLT-R-delayed recall) [ Designated as safety issue: No ]
  

• Cognitive function, specifically memory, 8 weeks, 16 weeks, and 12 months from the start of treatment as measured by the HVLT-R-delayed recall [ Designated as safety issue: No ]
  
• Neurocognitive failure as measured by a battery of tests [ Designated as safety issue: No ]
  
• Quality-of-life as measured by the Functional Assessment of Cancer Therapy Brain subscale (FACT-Br) [ Designated as safety issue: No ]
  
• Progression-free survival [ Designated as safety issue: No ]
  
• Overall survival [ Designated as safety issue: No ]
  
• Adverse events based on CTCAE 3.0 [ Designated as safety issue: Yes ]
  
• Collection of serum, plasma, buffy coat cells, urine, and cerebrospinal fluid for future translational research analyses [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine whether the addition of memantine hydrochloride to whole-brain radiotherapy (WBRT) preserves cognitive function, specifically memory, as measured by the Hopkins Verbal Learning Test for delayed recall (HVLT-delayed recall), over that of placebo and WBRT in patients with brain metastases at 24 weeks from the start of drug treatment.

Secondary

• Determine whether the addition of memantine hydrochloride preserves cognitive function, specifically memory, as measured by the HVLT-delayed recall at 8 weeks, 16 weeks, and 12 months from the start of drug treatment.
• Determine whether the addition of memantine hydrochloride increases time to neurocognitive failure as measured by cognitive decline on a battery of tests including the HVLT for free recall, delayed recall, and delayed recognition; the Controlled Word Association Test (COWAT); the Trail Making Test Parts A and B (TMT); the Medical Outcomes Scale-Cognitive Functioning Subscale (MOS); and the Mini-Mental Status Examination (MMSE).
• Evaluate the potential benefit of memantine hydrochloride in change and overall quality of life, as measured by the Functional Assessment of Cancer Therapy-Brain (FACT-Br) subscale.
• Determine whether the addition of memantine hydrochloride increases progression-free survival.
• Determine whether the addition of memantine hydrochloride increases overall survival.
• Compare adverse events between the treatment arms according to the CTCAE v3.0 criteria.
• Collect serum, plasma, buffy coat cells, urine, and CSF for future translational research analyses.

OUTLINE: This is a multicenter study. Patients are stratified according to recursive partitioning analysis (RPA) prognostic class (class I vs class II with controlled systemic disease) and prior surgical therapy (none vs radiosurgery or surgical resection). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo whole-brain radiotherapy (WBRT) 5 days a week for 3 weeks (15 fractions). Patients also receive oral memantine hydrochloride once daily beginning on day 1 of WBRT and continuing for 24 weeks.
• Arm II: Patients undergo WBRT as in arm I. Patients also receive oral placebo once daily beginning on day 1 of WBRT and continuing for 24 weeks.

After completion of study treatment, patients are followed at 6 months, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.