Memantine Hydrochloride and Whole-Brain Radiotherapy With or Without Hippocampal Avoidance in Reducing Neurocognitive Decline in Patients With Brain Metastases

Inclusion Criteria:

   - PRIOR TO STEP 1 REGISTRATION:

      - Brain metastases outside a 5-mm margin around either hippocampus must be visible
      on contrast-enhanced magnetic resonance imaging (MRI) performed =< 21 days prior
      to Step 1 registration; an allowed exception, regarding ability to image brain
      metastases, would be that patients who had undergone radiosurgery or surgical
      resection and are planning adjuvant WBRT do not have to have visible disease but
      do need a pre-surgery MRI or computed tomography (CT) scan demonstrating brain
      metastases; however, the brain metastases could not have been within 5 mm of
      either hippocampus

      - Patients must have a gadolinium contrast-enhanced three-dimensional spoiled
      gradient (SPGR), magnetization-prepared rapid gradient echo (MP-RAGE), or turbo
      field echo (TFE) axial MRI scan with standard axial and coronal gadolinium
      contrast-enhanced T1-weighted sequence and axial T2/FLAIR sequence acquisitions;
      to yield acceptable image quality, the gadolinium contrast-enhanced
      three-dimensional SPGR, MP-RAGE, or TFE axial MRI scan should use the smallest
      possible axial slice thickness not exceeding 1.5 mm; the associated coronal and
      sagittal contrast-enhanced T1 sequences can be up to 2.5 mm in slice thickness;
      this MRI must be obtained =< 21 days prior to step 1 registration; the vendor
      specific MRI protocols are available for download from the Alzheimer's Disease
      Neuroimaging Initiative (ADNI)

      - Patients must provide study-specific informed consent prior to registration

   - PRIOR TO STEP 2 REGISTRATION:

      - The following baseline neurocognitive assessments must be completed prior to Step
      2 registration: HVLT-R, TMT, and COWA;

      - Pathologically (histologically or cytologically) proven diagnosis of solid tumor
      malignancy within 5 years prior to Step 2 registration

      - History and physical examination within 28 days prior to Step 2 registration

      - Karnofsky performance status of >= 70 within 28 days prior to Step 2 registration

      - Serum creatinine =< 3 mg/dL (265 umol/L) and creatinine clearance >= 30 ml/min

      - Blood urea nitrogen (BUN) within institutional upper limit of normal (e.g. < 20
      mg/dL)

      - Total bilirubin =< 2.5 mg/dL (43 umol/L)

      - Patients may have had prior therapy for brain metastasis, including radiosurgery
      and surgical resection; patients must have completed prior therapy by at least 14
      days prior to Step 2 for surgical resection and 7 days for radiosurgery

      - Negative serum pregnancy test (in women of childbearing potential) =< 14 days
      prior to Step 2; women of childbearing potential and men who are sexually active
      must practice adequate contraception while on study

      - Patients who are primary English or French speakers are eligible

Exclusion Criteria:

   - Prior external beam radiation therapy to the brain or whole brain radiation therapy

   - Planned cytotoxic chemotherapy during the WBRT only; patients may have had prior
   chemotherapy

   - Radiographic evidence of hydrocephalus or other architectural distortion of the
   ventricular system, including placement of external ventricular drain or
   ventriculoperitoneal shunt

   - Severe, active co-morbidity defined as follows:

      - Unstable angina and/or congestive heart failure requiring hospitalization within
      the last 6 months

      - Transmural myocardial infarction within the last 6 months

      - Acute bacterial or fungal infection requiring intravenous antibiotics at the time
      of registration

      - Chronic obstructive pulmonary disease exacerbation or other acute respiratory
      illness precluding study therapy at the time of registration

      - Severe hepatic disease defined as a diagnosis of Child-Pugh class B or C hepatic
      disease

      - Renal tubular acidosis or metabolic acidosis

      - Human immunodeficiency virus (HIV) positive with cluster of differentiation (CD)4
      count < 200 cells/microliter; note that patients who are HIV positive are
      eligible, provided they are under treatment with highly active antiretroviral
      therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior
      to registration; Note also that HIV testing is not required for eligibility for
      this protocol

   - Pregnant or lactating women, or women of childbearing potential and men who are
   sexually active and not willing/able to use medically acceptable forms of
   contraception

   - Prior allergic reaction to memantine (memantine hydrochloride)

   - Current alcohol or drug abuse (may exacerbate lethargy/dizziness with memantine)

   - Intractable seizures while on adequate anticonvulsant therapy-more than 1 seizure per
   month for the past 2 months

   - Patients with definitive leptomeningeal metastases

   - Patients with brain metastases from primary germ cell tumors, small cell carcinoma,
   unknown primary, or lymphoma

   - Contraindication to magnetic resonance (MR) imaging such as implanted metal devices or
   foreign bodies

   - Contraindication to gadolinium contrast administration during MR imaging, such as
   allergy or insufficient renal function

   - Current use of (other N-methyl D-aspartate [NMDA] antagonists) amantadine, ketamine,
   or dextromethorphan